Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

PubMed

Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

2011-06-01

Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

More Than Cholesterol Transporters: Lipoprotein Receptors in CNS Function and Neurodegeneration

PubMed Central

Lane-Donovan, Courtney E.; Philips, Gary T.; Herz, Joachim

2014-01-01

Members of the low-density lipoprotein (LDL) receptor gene family have a diverse set of biological functions that transcend lipid metabolism. Lipoprotein receptors have broad effects in both the developing and adult brain and participate in synapse development, cargo trafficking, and signal transduction. In addition, several family members play key roles in Alzheimer's disease pathogenesis and neurodegeneration. This review summarizes our current understanding of the role lipoprotein receptors play in CNS function and AD pathology, with a special emphasis on amyloid-independent roles in endocytosis and synaptic dysfunction. PMID:25144875

Relationship between Depressive Symptoms and Cardiovascular Disease Risk Factors in African American Individuals

DTIC Science & Technology

2011-01-01

cholesterol , triglycerides , high - density cholesterol (HDL), and calculated low- density lipoprotein (LDL)), and blood glucose level. 2.3. Assessments 2.3.1...separately; BP: blood pressure; HDL: high - density lipoprotein ; LDL: low- density lipoprotein . at or above threshold with those who do not among a group of...261, 2001. [11] G. R. Warnick, R. H. Knopp, V. Fitzpatrick, and L. Branson, “Estimating low- density lipoprotein

New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs

PubMed Central

Norata, Giuseppe Danilo; Ballantyne, Christie M.; Catapano, Alberico Luigi

2013-01-01

Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach. PMID:23509227

Ultracentrifugal and electrophoretic characteristics of the plasma lipoproteins of miniature schnauzer dogs with idiopathic hyperlipoproteinemia.

PubMed

Whitney, M S; Boon, G D; Rebar, A H; Story, J A; Bottoms, G D

1993-01-01

To better characterize the idiopathic hyperlipoproteinemia of Miniature Schnauzer dogs, the plasma lipoproteins of 20 Miniature Schnauzers (MS) and 11 dogs of other breeds (DOB) were evaluated by ultracentrifugation, electrophoresis, and biochemical tests. Seventeen MS were healthy; 3 had diabetes mellitus. Plasma from 6 of 17 healthy and all 3 diabetic MS was visibly lipemic. Lipemia was slight to marked in healthy lipemic MS, and marked in diabetic ones. All DOB had clear plasma; 8 were healthy and 3 had diabetes. All healthy lipemic MS and diabetic lipemic MS had hypertriglyceridemia associated with excess very low density lipoproteins. Chylomicronemia was present in 4 of 6 healthy lipemic MS and all 3 diabetic lipemic MS. Lipoproteins with ultracentrifugal and electrophoretic characteristics of normal low density lipoprotein were lacking in 4 of 6 healthy lipemic MS. The lipoprotein patterns of 4 of 11 healthy nonlipemic MS were characterized by mild hypertriglyceridemia associated with increased very low density lipoproteins and a lack of lipoproteins with characteristics of normal low density lipoproteins. Lipoprotein patterns of diabetic DOB closely resembled those of healthy DOB; those of diabetic lipemic MS resembled those of markedly lipemic healthy lipemic MS. In conclusion, the hyperlipoproteinemia of Miniature Schnauzers is characterized by increased very low density lipoproteins with or without accompanying chylomicronemia; some affected dogs may have decreased low density lipoproteins.

Genome-wide association study indicates variants associated with insulin signaling and inflammation mediate lipoprotein responses to fenofibrate

USDA-ARS?s Scientific Manuscript database

A shift towards overall larger very low-density lipoprotein (VLDL), and smaller low-density lipoprotein and high-density lipoprotein (HDL) diameters occurs in insulin resistance (IR), which reflects shifts in the distribution of the subfraction concentrations. Fenofibrate, indicated for hypertriglyc...

Use of the TLX ultracentrifuge for the isolation of different density lipoproteins and effects of freeze/thawing of human plasma before ultracentrifugation.

PubMed

Charlton-Menys, Valentine; Chobotova, Jelena; Durrington, Paul N

2008-01-01

Isolation of different density lipoproteins by ultracentrifugation can require lengthy centrifugation times and freeze/thawing of plasma may influence recovery. We isolated a range of lipoproteins using a preparative ultracentrifuge and the TLX micro-ultracentrifuge and determined the effect of freeze/thawing of plasma beforehand. In fresh plasma, there was no significant difference in results for small-dense low-density lipoprotein apolipoprotein B (LDL apoB) (density >1.044 g/mL) or cholesterol at density >1.006 g/mL. Freeze/thawing had no effect on closely correlated results for small-dense LDL apoB (r=0.85; p<0.0001) or high-density lipoprotein (r=0.93; p<0.0001). The TLX micro-ultracentrifuge is a reliable alternative to the preparative ultracentrifuge and freeze/thawing has only a small effect on small-dense LDL apoB or high-density lipoprotein cholesterol.

Identification of the trypanocidal factor in normal human serum: high density lipoprotein.

PubMed Central

Rifkin, M R

1978-01-01

The differentiation of Trypanosoma brucei from T. rhodesiense, the causative agent of human sleeping sickness, depends on their relative sensitivities to the cytotoxic effects of normal human serum. The molecule responsible for the specific lysis of T. brucei has now been isolated. Serum lipoproteins were fractionated and purified by ultracentrifugal flotation and chromatography on Bio-Gel A-5m. Trypanocidal activity was recovered in the high density lipoprotein fraction (density, 1.063-1.216 g/ml). Contamination by other serum proteins was checked by crossed immunoelectrophoresis and sodium dodecyl sulfate/acrylamide gel electrophoresis. Only a trace of beta-lipoprotein was found. The trypanocidal activity of pure human high density lipoprotein was identical to that of unfractionated serum when the following were tested: (i) time course of in vitro lysis of T. bruceli; (ii) in vivo destruction of T. brucei; (iii) relative resistance of T. rhodesiense to lysis. Rat or rabbit high density lipoprotein had no trypanocidal activity. Identification of the trypanocidal factor as high density lipoprotein was confirmed by the finding that serum from patients with Tangier disease, an autosomal recessive disorder characterized by a severe deficiency of high density lipoprotein, had no trypanocidal activity. Images PMID:210461

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.

PubMed

Steffensen, Lasse Bach; Mortensen, Martin Bødtker; Kjolby, Mads; Hagensen, Mette Kallestrup; Oxvig, Claus; Bentzon, Jacob Fog

2015-09-01

Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated. In the present study, we examined whether a causal link exists between disturbed laminar flow and the ability of the arterial wall to retain lipoproteins. Lipoprotein retention was detected at natural predilection sites of the murine thoracic aorta 18 hours after infusion of fluorescently labeled low-density lipoprotein. To test for causality between blood flow and the ability of these areas to retain lipoproteins, we manipulated blood flow in the straight segment of the common carotid artery using a constrictive collar. Disturbed laminar flow did not affect low-density lipoprotein influx, but increased the ability of the artery wall to bind low-density lipoprotein. Concordantly, disturbed laminar flow led to differential expression of genes associated with phenotypic modulation of vascular smooth muscle cells, increased expression of proteoglycan core proteins associated with lipoprotein retention, and of enzymes responsible for chondroitin sulfate glycosaminoglycan synthesis and sulfation. Blood flow regulates genes associated with vascular smooth muscle cell phenotypic modulation, as well as the expression and post-translational modification of lipoprotein-binding proteoglycan core proteins, and the introduction of disturbed laminar flow vastly augments the ability of a previously resistant, straight arterial segment to retain lipoproteins. © 2015 American Heart Association, Inc.

Understanding Lipoproteins as Transporters of Cholesterol and Other Lipids

ERIC Educational Resources Information Center

Biggerstaff, Kyle D.; Wooten, Joshua S.

2004-01-01

A clear picture of lipoprotein metabolism is essential for understanding the pathophysiology of atherosclerosis. Many students are taught that low-density lipoprotein-cholesterol is "bad" and high-density lipoprotein-cholesterol is "good." This misconception leads to students thinking that lipoproteins are types of cholesterol rather than…

Effects of hormones on lipids and lipoproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, R.M.

1991-12-01

Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men andmore » are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.« less

Novel nonstatin strategies to lower low-density lipoprotein cholesterol.

PubMed

Davidson, Michael H

2009-01-01

There remains an unmet need to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients who are maximized on current therapy or intolerant to statins. Several novel agents have been developed to lower LDL-C, either as monotherapy or in combination with statins. These novel therapies include squalene synthase inhibitors, microsomal triglyceride transfer protein inhibitors, and antisense apolipoprotein B. Although each of these novel therapies effectively lowers LDL-C, challenges remain in the clinical development to assess long-term safety.

Liver histology during Mipomersen therapy for severe hypercholesterolemia.

PubMed

Hashemi, Nikroo; Odze, Robert D; McGowan, Mary P; Santos, Raul D; Stroes, Erik S G; Cohen, David E

2014-01-01

Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B synthesis and lowers plasma low-density lipoprotein cholesterol even in the absence of low-density lipoprotein receptor function, presumably from inhibition of hepatic production of triglyceride-rich very low-density lipoprotein particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time. The objective of this study was to assess the liver biopsy findings in patients treated with mipomersen. We describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist. The histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis. These findings suggest that hepatic steatosis resulting from mipomersen is distinct from nonalcoholic steatohepatitis. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Elevation of small, dense low density lipoprotein cholesterol-a possible antecedent of atherogenic lipoprotein phenotype in type 2 diabetes patients in Jos, North-Central Nigeria.

PubMed

Inaku, Kenneth O; Ogunkeye, Obasola O; Abbiyesuku, Fayeofori M; Chuhwak, Evelyn K; Isichei, Christian O; Imoh, Lucius C; Amadu, Noel O; Abu, Alexander O

2017-01-01

The global prevalence of type 2 diabetes is increasing. Dyslipidaemia is a known complication of diabetes mellitus manifesting frequently as cardiovascular diseases and stoke. Elevation of small, dense low density lipoprotein has been recognised as a component of the atherogenic lipoprotein phenotype associated with cardiovascular complications. We speculate that the elevation of this lipoprotein particle may be the antecedent of the atherogenic lipoprotein phenotype. This study therefore aims to determine the pattern of dyslipidaemia among diabetes mellitus patients in Jos, North-Central Nigeria. One hundred and seventy-six patients with type 2 diabetes and 154 age-matched controls were studied. The patients with diabetes were regular clinic attenders and had stable glycaemic control. None were on lipid-lowering therapy. Anthropometric indices, blood pressure, and lipids (including total cholesterol, high density lipoprotein cholesterol, and triglyceride) were measured by chemical methods using the Hitachi 902 analyzer. Low density lipoprotein cholesterol was calculated using the Friedewald's equation. Small, dense low density lipoprotein cholesterol, -sdLDL-C was measured using the precipitation method by Hirano et al. Means of the different groups were compared using EPI Info and a P -value of <0.05 was accepted as significant difference. Total cholesterol, low density lipoprotein cholesterol, triglyceride and small, dense lipoprotein cholesterol were all significantly higher in diabetes patients than controls except high density lipoprotein cholesterol. The percentage of LDL-C as sdLDL-C among the diabetes versus control group was 45% ± 17.79 v 32.0% ± 15.93. Serum sdLDL-C concentration was determined to be 1.45 ± 0.64 among diabetes patients and 0.8 ± 0.54 among control subjects. 75% of diabetes patients had hypertension and were taking blood pressure lowering medications. The classical atherogenic lipoprotein phenotype was not demonstrated among subjects with type 2 diabetes mellitus in this study, but the elevation of serum small dense low density lipoprotein cholesterol in patients with sustained hypertension suggests the establishment of atherogenic complications among our diabetes patients.

Analysis of lipoprotein profiles of healthy cats by gel-permeation high-performance liquid chromatography

PubMed Central

MIZUTANI, Hisashi; SAKO, Toshinori; OKUDA, Hiroko; ARAI, Nobuaki; KURIYAMA, Koji; MORI, Akihiro; YOSHIMURA, Itaru; KOYAMA, Hidekazu

2016-01-01

Density gradient ultracentrifugation (DGUC) and gel electrophoresis are conventionally used to obtain lipoprotein profiles of animals. We recently applied high-performance liquid chromatography with a gel permeation column (GP-HPLC) and an on-line dual enzymatic system to dogs for lipoprotein profile analysis. We compared the GP-HPLC with DGUC as a method to obtain a feline lipoprotein profile. The lipoprotein profiles showed large and small peaks, which corresponded to high-density lipoprotein (HDL) and low-density lipoprotein (LDL), respectively, whereas very low-density lipoprotein (VLDL) and chylomicron (CM) were only marginally detected. This profile was very similar to that of dogs reported previously. Healthy cats also had a small amount of cholesterol-rich particles distinct from the normal LDL or HDL profile. There was no difference in lipoprotein profiles between the sexes, but males had a significantly larger LDL particle size (P=0.015). This study shows the feasibility of GP-HPLC for obtaining accurate lipoprotein profiles with small sample volumes and provides valuable reference data for healthy cats that should facilitate diagnoses. PMID:27170431

The Effects of Extended Release Niacin on Lipoprotein Sub-Particle Concentrations in HIV-Infected Patients

PubMed Central

Lin, Chunrong; Grandinetti, Andrew; Shikuma, Cecilia; Souza, Scott; Parikh, Nisha; Nakamoto, Beau; Kallianpur, Kalpana J

2013-01-01

With the advent of highly active antiretroviral therapy (HAART), Cardiovascular Disease (CVD) has emerged as the leading cause of death in Human Immunodeficiency Virus (HIV) infected patients. An atherogenic lipoprotein phenotype has been described in HIV- infected patients with a predominance of small, low density lipoprotein (SLDL) particles with accompanying elevated triglycerides and reduced high density lipoprotein cholesterol. This randomized controlled pilot study was conducted to evaluate the efficacy of Extended Release Niacin (ERN) in improving the lipid profile in HIV patients. A total of 17 HIV positive subjects on HAART therapy with High Density Lipoprotein Cholesterol (HDL) levels below 40mg/dl and Low Density Lipoprotein Cholesterol (LDL) below 130mg/dl were enrolled. Nine were randomized to be treated with ERN titrated from a starting level of 500mg/night and titrated to a level of 1500mg/night. Eight patients were assigned to the control arm. No placebo was used. Lipoprotein profiles of the subjects were analyzed at baseline and at the end of 12 weeks using Nuclear Magnetic Resonance (NMR) spectroscopy. At the end of 12 weeks, NMR spectroscopic analysis revealed a significant increase in overall LDL size (1.2% in ERN treated subjects vs 2.0% decrease in control patients, P=.04) and a decrease in small LDL particle concentration (17.0% in ERN treated subjects vs 21.4% increase in control patients, P=.03) in subjects receiving ERN as compared to those in the control group. Only 1 subject receiving ERN developed serious flushing which was attributed to an accidental overdose of the drug. This pilot study demonstrates that ERN therapy in HIV-infected patients with low HDL is safe and effective in improving the lipoprotein profile in these patients. PMID:23795312

Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function

PubMed Central

Mak, Angel C. Y.; Pullinger, Clive R.; Tang, Ling Fung; Wong, Jinny S.; Deo, Rahul C.; Schwarz, Jean-Marc; Gugliucci, Alejandro; Movsesyan, Irina; Ishida, Brian Y.; Chu, Catherine; Poon, Annie; Kim, Phillip; Stock, Eveline O.; Schaefer, Ernst J.; Asztalos, Bela F.; Castellano, Joseph M.; Wyss-Coray, Tony; Duncan, Jacque L.; Miller, Bruce L.; Kane, John P.; Kwok, Pui-Yan; Malloy, Mary J.

2016-01-01

IMPORTANCE The identification of a patient with a rare form of severe dysbetalipoproteinemia allowed the study of the consequences of total absence of apolipoprotein E (apoE). OBJECTIVES To discover the molecular basis of this rare disorder and to determine the effects of complete absence of apoE on neurocognitive and visual function and on lipoprotein metabolism. DESIGN, SETTING, AND PARTICIPANTS Whole-exome sequencing was performed on the patient’s DNA. He underwent detailed neurological and visual function testing and lipoprotein analysis. Lipoprotein analysis was also performed in the Cardiovascular Research Institute, University of California, San Francisco, on blood samples from the proband’s mother, wife, 2 daughters, and normolipidemic control participants. MAIN OUTCOME MEASURES Whole-exome sequencing, lipoprotein analysis, and neurocognitive function. RESULTS The patient was homozygous for an ablative APOE frameshift mutation (c.291del, p.E97fs). No other mutations likely to contribute to the phenotype were discovered, with the possible exception of two, in ABCC2 (p.I670T) and LIPC (p.G137R). Despite complete absence of apoE, he had normal vision, exhibited normal cognitive, neurological, and retinal function, had normal findings on brain magnetic resonance imaging, and had normal cerebrospinal fluid levels of β-amyloid and tau proteins. He had no significant symptoms of cardiovascular disease except a suggestion of myocardial ischemia on treadmill testing and mild atherosclerosis noted on carotid ultrasonography. He had exceptionally high cholesterol content (760 mg/dL; to convert to millimoles per liter, multiply by 0.0259) and a high cholesterol to triglycerides ratio (1.52) in very low-density lipoproteins with elevated levels of small-diameter high-density lipoproteins, including high levels of prebeta-1 high-density lipoprotein. Intermediate-density lipoproteins, low-density lipoproteins, and very low-density lipoproteins contained elevated apoA-I and apoA-IV levels. The patient’s apoC-III and apoC-IV levels were decreased in very low-density lipoproteins. Electron microscopy revealed large lamellar particles having electron-opaque cores attached to electron-lucent zones in intermediate-density and low-density lipoproteins. Low-density lipoprotein particle diameters were distributed bimodally. CONCLUSIONS AND RELEVANCE Despite a profound effect on lipoprotein metabolism, detailed neurocognitive and retinal studies failed to demonstrate any defects. This suggests that functions of apoE in the brain and eye are not essential or that redundant mechanisms exist whereby its role can be fulfilled. Targeted knockdown of apoE in the central nervous system might be a therapeutic modality in neurodegenerative disorders. PMID:25111166

Evaluation of Lipid Profile in Patients with Cherry Angioma: A Case-Control Study in Guilan, Iran.

PubMed

Darjani, Abbas; Rafiei, Rana; Shafaei, Sareh; Rafiei, Elahe; Eftekhari, Hojat; Alizade, Narges; Gharaei Nejad, Kaveh; Rafiee, Behnam; Najirad, Sara

2018-01-01

Cherry angioma is the most common type of acquired cutaneous vascular proliferation which would increase with aging due to some angiogenic factors but the exact pathogenesis is unknown. Usually angiogenic factors are synthesized in human body to compensate occlusive effects of atherogenic agents such as serum lipids. Our hypothesis was that increased levels of these angiogenic factors could be a trigger for development of cherry angioma. This study has been designed to compare frequency of dyslipidemia in subjects with and without cutaneous cherry angioma. In this case-control study, 122 cases with cherry angioma and 122 control subjects without cherry angioma were enrolled. Demographic characteristics, number of the cherry angioma lesions, and serum lipid profile were collected for all subjects. The data was analyzed using SPSS 18 software. Mean levels of the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were higher in patients with cherry angioma compared to control subjects in which differences were significant for total cholesterol, low-density lipoprotein, and triglyceride ( P < 0.05) but not for high-density lipoprotein level. Serum lipids may have a role in producing angiogenic factors and development of cherry angioma and it seems logical to evaluate lipid profile in these cases.

Geometrical separation method for lipoproteins using bioformulated-fiber matrix electrophoresis: size of high-density lipoprotein does not reflect its density.

PubMed

Tabuchi, Mari; Seo, Makoto; Inoue, Takayuki; Ikeda, Takeshi; Kogure, Akinori; Inoue, Ikuo; Katayama, Shigehiro; Matsunaga, Toshiyuki; Hara, Akira; Komoda, Tsugikazu

2011-02-01

The increasing number of patients with metabolic syndrome is a critical global problem. In this study, we describe a novel geometrical electrophoretic separation method using a bioformulated-fiber matrix to analyze high-density lipoprotein (HDL) particles. HDL particles are generally considered to be a beneficial component of the cholesterol fraction. Conventional electrophoresis is widely used but is not necessarily suitable for analyzing HDL particles. Furthermore, a higher HDL density is generally believed to correlate with a smaller particle size. Here, we use a novel geometrical separation technique incorporating recently developed nanotechnology (Nata de Coco) to contradict this belief. A dyslipidemia patient given a 1-month treatment of fenofibrate showed an inverse relationship between HDL density and size. Direct microscopic observation and morphological observation of fractionated HDL particles confirmed a lack of relationship between particle density and size. This new technique may improve diagnostic accuracy and medical treatment for lipid related diseases.

Synthetic high-density lipoprotein nanoconjugate targets neuroblastoma stem cells, blocking migration and self-renewal.

PubMed

Subramanian, Chitra; White, Peter T; Kuai, Rui; Kalidindi, Avinaash; Castle, Valerie P; Moon, James J; Timmermann, Barbara N; Schwendeman, Anna; Cohen, Mark S

2018-05-09

Pathways critical for neuroblastoma cancer stem cell function are targeted by 4,19,27-triacetyl withalongolide A (WGA-TA). Because neuroblastoma cells and their cancer stem cells highly overexpress the scavenger receptor class B type 1 receptor that binds to synthetic high-density lipoprotein, we hypothesized that a novel mimetic synthetic high-density lipoprotein nanoparticle would be an ideal carrier for the delivery of 4,19,27-triacetyl withalongolide to neuroblastoma and neuroblastoma cancer stem cells. Expression of scavenger receptor class B type 1 in validated human neuroblastoma cells was evaluated by quantitative polymerase chain reaction (qPCR) and Western blot. In vitro cellular uptake of synthetic high-density lipoprotein nanoparticles was observed with a fluorescence microscope. In vivo biodistribution of synthetic high-density lipoprotein nanoparticles was investigated with IVIS imaging. Self-renewal and migration/invasion were assessed by sphere formation and Boyden chamber assays, respectively. Viability was analyzed by CellTiter-Glo assay. Cancer stem cell markers were evaluated by flow cytometry. qPCR and Western blot analysis revealed a higher level of scavenger receptor class B type 1 expression and drug uptake in N-myc amplified neuroblastoma cells. In vitro uptake of synthetic high-density lipoprotein was almost completely blocked by excess synthetic high-density lipoprotein. The synthetic high-density lipoprotein nanoparticles mainly accumulated in the tumor and liver, but not in other organs. Synthetic HDL-4,19,27-triacetyl withalongolide showed a 1,000-fold higher potency than the carrier (synthetic high-density lipoprotein) alone (P < .01) to kill neuroblastoma cells. Additionally, a dose-dependent decrease in sphere formation, invasion, migration, and cancer stem cell markers was observed after treatment of neuroblastoma cells with synthetic high-density lipoprotein-4,19,27-triacetyl withalongolide A. Synthetic high-density lipoprotein is a promising platform to improve the delivery of anticancer drug 4,19,27-triacetyl withalongolide A to neuroblastomas and neuroblastoma cancer stem cells through SR-B1 targeting in vitro and in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

How do eggs get fat? Insights into ovarian fatty acid accumulation in the shortfinned eel, Anguilla australis.

PubMed

Damsteegt, Erin L; Mizuta, Hiroko; Hiramatsu, Naoshi; Lokman, P Mark

2015-09-15

Previous research using eels has shown that 11-ketotestosterone can induce ovarian triacylglyceride accumulation both in vivo and in vitro. Further, accumulation is dramatically enhanced in the presence of very-low density lipoprotein. This study examined the involvement of the low density lipoprotein receptor and vitellogenin receptor in oocyte lipid accumulation. Specific antisera were used in an attempt to block the vitellogenin receptor and/or the low density lipoprotein receptor. Accordingly, incubation with the low density lipoprotein receptor antiserum clearly reduced the oocyte diameter and the amount of oil present within the oocyte. In contrast, blocking the vitellogenin receptor had little effect on either oocyte surface area or the abundance of oil droplets in the cytosol. In keeping with birds, we conclude that the low density lipoprotein receptor is a major player involved in mediating ovarian fatty acid accumulation in the eel. However, lipoprotein lipase-mediated fatty acid accumulation also remains conceivable, for example through interactions between this enzyme and the low density lipoprotein receptor. Copyright © 2015 Elsevier Inc. All rights reserved.

Evolving targets for lipid-modifying therapy

PubMed Central

Do, Rose Q; Nicholls, Stephen J; Schwartz, Gregory G

2014-01-01

The pathogenesis and progression of atherosclerosis are integrally connected to the concentration and function of lipoproteins in various classes. This review examines existing and emerging approaches to modify low-density lipoprotein and lipoprotein (a), triglyceride-rich lipoproteins, and high-density lipoproteins, emphasizing approaches that have progressed to clinical evaluation. Targeting of nuclear receptors and phospholipases is also discussed. PMID:25172365

Effect of phospholipase A treatment of low density lipoproteins on the dextran sulfate--lipoprotein interaction.

PubMed

Nishida, T

1968-09-01

The effect of phospholipase A on the interaction of low density lipoproteins of the S(f) 0-10 class with dextran sulfate was studied in phosphate buffer of pH 7.4, ionic strength 0.1, by chemical, spectrophotometric, and centrifugal methods. When low density lipoproteins that had been treated with phospholipase A were substituted for untreated lipoproteins, the amount of insoluble dextran sulfate-lipoprotein complex formed was greatly reduced. Hydrolysis of over 20% of the lecithin and phosphatidyl ethanolamine constituents of the lipoproteins prevented the formation of insoluble complex. However, even the lipoproteins in which almost all the phosphoglycerides were hydrolyzed produced soluble complex, which was converted to insoluble complex upon addition of magnesium sulfate. It is apparent that the lipoproteins altered extensively by treatment with phospholipase A retain many characteristic properties of native low density lipoproteins. Fatty acids, but not lysolecithin, released by the action of phospholipase A interfered with the formation of insoluble complex; this interference was due to association of the fatty acids with the lipoproteins. With increases in the concentration of the associated fatty acids, the amounts of magnesium ion required for the conversion of soluble complex to insoluble complex increased progressively. Charge interaction is evidently of paramount importance in the formation of sulfated polysaccharide-lipoprotein complexes.

Cardiovascular disease parameters in periodontitis.

PubMed

Monteiro, Andréa M; Jardini, Maria A N; Alves, Sarah; Giampaoli, Viviana; Aubin, Elisete C Q; Figueiredo Neto, Antônio M; Gidlund, Magnus

2009-03-01

Recently, there has been an increasing in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aim of this study is to investigate the association between chronic periodontitis and cardiovascular risk markers. Forty patients with periodontitis and 40 healthy gender-, body mass index-, and age-matched individuals were compared by measuring total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, levels of cytokines, antibodies against oxidized low-density lipoprotein, thiobarbituric acid reactive substances, total and differential white blood cell counts, and the non-linear index of refraction. The levels of triglycerides and high-density lipoprotein in periodontitis patients were significantly higher and lower, respectively (P = 0.002 and P = 0.0126), compared to controls. Total cholesterol, low-density lipoprotein, and lipid peroxide levels were the same in both groups (P = 0.2943, P = 0.1284, and P = 0.067, respectively). Interleukin (IL)-6 and -8, antibodies against oxidized low-density lipoprotein, and leukocyte and neutrophil counts were significantly higher in periodontitis patients (P <0.05). The value of the non-linear index of refraction of low-density lipoprotein solutions was higher in the controls (P = 0.015) compared to individuals with periodontitis. Our results confirmed and further strengthened the suggested association between coronary artery disease and periodontitis.

Pharmacological Regulation of Peroxisome Number in Glia

DTIC Science & Technology

2008-09-01

histone deacetylase HDL high - density lipoprotein LXR liver X receptor NPC Niemann Pick type C disease PBD peroxisome...transporters ABCA1 and ABCG1 with lipoproteins in the extracellular space, such as apoE; transportation to the liver occurs via high density lipoprotein ...mechanisms involved in the athero-protective effect of high density lipoproteins . Journal of internal medicine, 263, 256-273. Tobin, K. A., Steineger, H

Isolation and characterization of multivesicular bodies from rat hepatocytes: an organelle distinct from secretory vesicles of the Golgi apparatus

PubMed Central

1985-01-01

Hepatocytes of estradiol-treated rats, which express many low density lipoprotein receptors, rapidly accumulate intravenously injected low density lipoprotein in multivesicular bodies (MVBs). We have isolated MVBs and Golgi apparatus fractions from livers of estradiol-treated rats. MVB fractions were composed mainly of large vesicles, approximately 0.55 micron diam, filled with remnantlike very low density lipoproteins, known to be taken up into hepatocytes by receptor- mediated endocytosis. MVBs also contained numerous small vesicles, 0.05- 0.07 micron in diameter, and had two types of appendages: one fingerlike and electron dense and the other saclike and electron lucent. MVBs contained little galactosyltransferase or arylsulfatase activity, and content lipoproteins were largely intact. Very low density lipoproteins from Golgi fractions, which are derived to a large extent from secretory vesicles, were larger than those of MVB fractions and contained newly synthesized triglycerides. Membranes of MVBs contained much more cholesterol and less protein than did Golgi membranes. We conclude that two distinct lipoprotein-filled organelles are located in the bile canalicular pole of hepatocytes. MVBs, a major prelysosomal organelle of low density in the endocytic pathway, contain remnants of triglyceride-rich lipoproteins, whereas secretory vesicles of the Golgi apparatus contain nascent very low density lipoproteins. PMID:3988801

Preoperative serum lipids as prognostic predictors in esophageal squamous cell carcinoma patients with esophagectomy.

PubMed

Chen, Pengxiang; Han, Lihui; Wang, Cong; Jia, Yibin; Song, Qingxu; Wang, Jianbo; Guan, Shanghui; Tan, Bingxu; Liu, Bowen; Jia, Wenqiao; Cui, Jianfeng; Zhou, Wei; Cheng, Yufeng

2017-06-20

This study was to evaluate the prognostic significance of serum lipids in esophageal squamous cell carcinoma patients who underwent esophagectomy. Preoperative serum lipids were collected from 214 patients who were diagnosed with esophageal squamous cell carcinoma. All of the patients received esophagectomy in Qilu Hospital of Shandong University from January 2007 to December 2008. The records and data were analyzed retrospectively. We found that low total cholesterol (for T stage, p = 0.006; for TNM stage, p = 0.039) and low-density lipoprotein cholesterol (for T stage, p = 0.031; for TNM stage, p = 0.035) were associated with advanced T stage and TNM stage. Kaplan-Meier survival analysis indicated that low total cholesterol and low-density lipoprotein cholesterol were associated with shorter disease-free survival(for total cholesterol, p = 0.045; for low-density lipoprotein cholesterol, p < 0.001) and overall survival (for total cholesterol, p = 0.043; for low-density lipoprotein cholesterol, p < 0.001). Lower low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LHR) indicated poorer disease-free survival and overall survival (both p < 0.001). In the multivariate analysis, low-density lipoprotein cholesterol and LHR were independent prognostic factors for disease-free survival and overall survival. In conclusion, our study indicated that preoperative serum total cholesterol and low-density lipoprotein cholesterol are prognostic factors for esophageal squamous cell carcinoma patients who underwent esophagectomy. LHR can serve as a promising serum lipids-based prognostic indicator.

Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function.

PubMed

Gillard, Baiba K; Raya, Joe L; Ruiz-Esponda, Raul; Iyer, Dinakar; Coraza, Ivonne; Balasubramanyam, Ashok; Pownall, Henry J

2013-07-01

HIV patients on antiretroviral therapy (HIV/ART) exhibit a unique atherogenic dyslipidemic profile with hypertriglyceridemia (HTG) and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. In the Heart Positive Study of HIV/ART patients, a hypolipidemic therapy of fenofibrate, niacin, diet, and exercise reduced HTG and plasma non-HDL cholesterol concentrations and raised plasma HDL cholesterol and adiponectin concentrations. We tested the hypothesis that HIV/ART HDL have abnormal structures and properties and are dysfunctional. Hypolipidemic therapy reduced the TG contents of low-density lipoprotein and HDL. At baseline, HIV/ART low-density lipoproteins were more triglyceride (TG)-rich and HDL were more TG- and cholesteryl ester-rich than the corresponding lipoproteins from normolipidemic (NL) subjects. Very-low-density lipoproteins, low-density lipoprotein, and HDL were larger than the corresponding lipoproteins from NL subjects; HIV/ART HDL were less stable than NL HDL. HDL-[(3)H]cholesteryl ester uptake by Huh7 hepatocytes was used to assess HDL functionality. HIV/ART plasma were found to contain significantly less competitive inhibition activity for hepatocyte HDL-cholesteryl ester uptake than NL plasma were found to contain (P<0.001). Compared with NL subjects, lipoproteins from HIV/ART patients are larger and more neutral lipid-rich, and their HDL are less stable and less receptor-competent. On the basis of this work and previous studies of lipase activity in HIV, we present a model in which plasma lipolytic activities or hepatic cholesteryl ester uptake are impaired in HIV/ART patients. These findings provide a rationale to determine whether the distinctive lipoprotein structure, properties, and function of HIV/ART HDL predict atherosclerosis as assessed by carotid artery intimal medial thickness.

[Residual risk: The roles of triglycerides and high density lipoproteins].

PubMed

Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

2016-06-01

In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. © Georg Thieme Verlag KG Stuttgart · New York.

Targeting Apolipoproteins in Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Sriram, Renuka; Lagerstedt, Jens O.; Samardzic, Haris; Kreutzer, Ulrike; Petrolova, Jitka; Xie, Hongtao; Kaysen, George A.; Voss, John C.; Desreux, Jean F.; Jue, Thomas

Maintaining normal physiological homeostasis depends upon a coordinated metabolism of both water-soluble and -insoluble substrates. In humans the body derives these molecules — such as glucose, amino acids, and fatty acids — from complex food matter. Water-soluble substrates can circulate readily in blood, while water-insoluble molecules — such as fatty acid, triacylglycerol, and cholesterol — require ampiphathic carriers to transport them from the site of biosynthesis (liver and intestine) to the target tissue. For fatty acid, albumin serves as the major transporter. For triacylglycerol and cholesterol, however, macromolecular complexes aggregate the hydrophobic molecules into the core and cover the surface with amphiphatic proteins and phospholipids to solubilize the particles in the lymphatic and circulatory systems. These macromolecules belong to a class of proteins, plasma lipoproteins, with specific functions and cellular targets. In the clinic these lipoproteins prognosticate the risk of cardiovascular disease (CVD). Lipoproteins divide usually into five major types: chylomicron, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Each lipoprotein type exhibits characteristic density, size, and composition. As implied in the name, the density varies from the low-density chylomicron (<0.95 g/ml) to the high-density HDL (1.2 g/ml). Size also varies. The chylomicron has the largest diameter (75-1,200 nm), and HDL has the smallest (5-12 nm). The physical property variation arises from each lipoprotein's distinct composition. In a chylomicron, cholesterol, triacylglycerol, and phospholipid predominate and constitute about 90% of the particle. Protein constitutes only about 10%. In contrast, the smaller HDL has less cholesterol, triacylglycerol, and phospholipid (65% of the particle) but more protein (over 30%).

Association of height and pubertal timing with lipoprotein subclass profile: exploring the role of genetic and environmental effects.

PubMed

Jelenkovic, Aline; Bogl, Leonie H; Rose, Richard J; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Kaprio, Jaakko; Silventoinen, Karri

2013-01-01

Little is known about the relationship between growth and lipoprotein profile. We aimed to analyze common genetic and environmental factors in the association of height from late childhood to adulthood and pubertal timing with serum lipid and lipoprotein subclass profile. A longitudinal cohort of Finnish twin pairs (FinnTwin12) was analyzed using self-reported height at 11-12, 14, 17 years and measured stature at adult age (21-24 years). Data were available for 719 individual twins including 298 complete pairs. Serum lipids and lipoprotein subclasses were measured by proton nuclear magnetic resonance spectroscopy. Multivariate variance component models for twin data were fitted. Cholesky decomposition was used to partition the phenotypic covariation among traits into additive genetic and unique environmental correlations. In men, the strongest associations for both adult height and puberty were observed with total cholesterol, low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, and low-density lipoprotein particle subclasses (max. r = -0.19). In women, the magnitude of the correlations was weaker (max. r = -0.13). Few associations were detected between height during adolescence and adult lipid profile. Early onset of puberty was related to an adverse lipid profile, but delayed pubertal development in girls was associated with an unfavorable profile, as well. All associations were mediated mainly by additive genetic factors, but unique environmental effects cannot be disregarded. Early puberty and shorter adult height relate to higher concentrations of atherogenic lipids and lipoprotein particles in early adulthood. Common genetic effects behind these phenotypes substantially contribute to the observed associations. Copyright © 2013 Wiley Periodicals, Inc.

High-density lipoprotein cholesterol subfractions and lecithin: cholesterol acyltransferase activity in collegiate soccer players.

PubMed

Imamura, H; Nagata, A; Oshikata, R; Yoshimura, Y; Miyamoto, N; Miyahara, K; Oda, K; Iide, K

2013-05-01

Many of the published data on the lipid profile of athletes is based on studies of endurance athletes. The data on soccer players are rare. The purpose of this study was to examine serum high-density lipoprotein cholesterol subfractions and lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31 well-trained male collegiate soccer players were divided into 2 groups: 16 defenders and 15 offenders. They were compared with 16 sedentary controls. Dietary information was obtained with a food frequency questionnaire. The subjects were all non-smokers and were not taking any drug known to affect the lipid and lipoprotein metabolism. The offenders had significantly higher high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and apolipoprotein A-I than the defenders and controls, whereas the defenders had the significantly higher high-density lipoprotein2 cholesterol than the controls. Both groups of athletes had significantly higher lecithin:cholesterol acyltransferase activity than the controls. The results indicate that favorable lipid and lipoprotein profile could be obtained by vigorous soccer training. © Georg Thieme Verlag KG Stuttgart · New York.

Native and Reconstituted Plasma Lipoproteins in Nanomedicine: Physicochemical Determinants of Nanoparticle Structure, Stability, and Metabolism

PubMed Central

Pownall, Henry J.; Rosales, Corina; Gillard, Baiba K.; Ferrari, Mauro

2016-01-01

Although many acute and chronic diseases are managed via pharmacological means, challenges remain regarding appropriate drug targeting and maintenance of therapeutic levels within target tissues. Advances in nanotechnology will overcome these challenges through the development of lipidic particles, including liposomes, lipoproteins, and reconstituted high-density lipoproteins (rHDL) that are potential carriers of water-soluble, hydrophobic, and amphiphilic molecules. Herein we summarize the properties of human plasma lipoproteins and rHDL, identify the physicochemical determinants of lipid transfer between phospholipid surfaces, and discuss strategies for increasing the plasma half-life of lipoprotein- and liposome-associated molecules. PMID:27826368

Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

PubMed

Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

2015-02-13

Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery.

PubMed

Zhang, Xueqin; Huang, Gangliang

2017-12-01

High-density lipoprotein (HDL) and low-density lipoprotein (LDL), as human endogenous lipoprotein particles, have low toxicity, high selectivity, and good safety. They can avoid the recognition and clearance of human reticuloendothelial system. These synthetic lipoproteins (sLPs) have been attracted extensive attention as the nanovectors for tumor-targeted drug and gene delivery. Herein, recent advances in the field of anticancer based on these two lipid proteins and recombinant lipoproteins (rLPs) as target delivery vectors were analyzed and discussed.

Non-high-density lipoprotein cholesterol: an important predictor of stroke and diabetes-related mortality in Japanese elderly diabetic patients.

PubMed

Araki, Atsushi; Iimuro, Satoshi; Sakurai, Takashi; Umegaki, Hiroyuki; Iijima, Katsuya; Nakano, Hiroshi; Oba, Kenzo; Yokono, Koichi; Sone, Hirohito; Yamada, Nobuhiro; Ako, Junya; Kozaki, Koichi; Miura, Hisayuki; Kashiwagi, Atsunori; Kikkawa, Ryuichi; Yoshimura, Yukio; Nakano, Tadasumi; Ohashi, Yasuo; Ito, Hideki

2012-04-01

To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients. This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥ 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry. During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non-high-density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P < 0.001) for diabetes-related death and 1.008 (1.002-1.014; P < 0.001) for total diabetes-related events. Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients. © 2012 Japan Geriatrics Society.

Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

PubMed

Rolla, Roberta; De Mauri, Andreana; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

2015-12-01

Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

Interleukins 6 and 8 and abdominal fat depots are distinct correlates of lipid moieties in healthy pre- and postmenopausal women.

PubMed

Veldhuis, Johannes D; Dyer, Roy B; Trushin, Sergey A; Bondar, Olga P; Singh, Ravinder J; Klee, George G

2016-12-01

Available data associate lipids concentrations in men with body mass index, anabolic steroids, age, and certain cytokines. Data were less clear in women, especially across the full adult lifespan, and when segmented by premenopausal and postmenopausal status. 120 healthy women (60 premenopausal and 60 postmenopausal) in Olmsted County, MN, USA, a stable well studied clinical population. Dependent variables: measurements of 10 h fasting high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, and triglycerides. testosterone, estrone, estradiol, 5-alpha-dihydrotestosterone, and sex-hormone binding globulin (by mass spectrometry); insulin, glucose, and albumin; abdominal visceral, subcutaneous, and total abdominal fat [abdominal visceral fat, subcutaneous fat, total abdominal fat by computerized tomography scan]; and a panel of cytokines (by enzyme-linked immunosorbent assay). Multivariate forward-selection linear-regression analysis was applied constrained to P < 0.01. Lifetime data: High-density lipoprotein cholesterol was correlated jointly with age (P < 0.0001, positively), abdominal visceral fat (P < 0.0001, negatively), and interleukin-6 (0.0063, negatively), together explaining 28.1 % of its variance (P = 2.3 × 10 -8 ). Total cholesterol was associated positively with multivariate age only (P = 6.9 × 10 -4 , 9.3 % of variance). Triglycerides correlated weakly with sex-hormone binding globulin (P = 0.0115), and strongly with abdominal visceral fat (P < 0.0001), and interleukin-6 (P = 0.0016) all positively (P = 1.6 × 10 -12 , 38.9 % of variance). Non high-density lipoprotein cholesterol and low-density lipoprotein cholesterol correlated positively with both total abdominal fat and interleukin-8 (P = 2.0 × 10 -5 , 16.9 % of variance; and P = 0.0031, 9.4 % of variance, respectively). Premenopausal vs. postmenopausal comparisons identified specific relationships that were stronger in premenopausal than postmenopausal individuals, and vice versa. Age was a stronger correlate of low-density lipoprotein cholesterol; interleukin-6 of triglycerides and high-density lipoprotein; and both sex-hormone binding globulin and total abdominal fat of non high-density lipoprotein cholesterol in premenopausal than postmenopausal women. Conversely, sex-hormone binding globulin, abdominal visceral fat, interleukin-8, adiponectin were stronger correlates of triglycerides; abdominal visceral fat, and testosterone of high-density lipoprotein cholesterol; and age of both non high-density lipoprotein and low-density lipoprotein in postmenopausal than premenopausal women. Our data delineate correlations of total abdominal fat and interleukin-8 (both positively) with non high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in healthy women across the full age range of 21-79 years along with even more specific associations in premenopausal and postmenopausal individuals. Whether some of these outcomes reflect causal relationships would require longitudinal and interventional or genetic studies.

Genome-wide association studies identified novel loci for non-high-density lipoprotein cholesterol and its postprandial lipemic response

USDA-ARS?s Scientific Manuscript database

Non-high-density lipoprotein cholesterol (NHDL) is an independent and superior predictor of CVD risk as compared to low-density lipoprotein alone. It represents a spectrum of atherogenic lipid fractions with possibly a distinct genomic signature. We performed genome-wide association studies (GWAS) t...

Effects of an evidence-based computerized virtual clinician on low-density lipoprotein and non-high-density lipoprotein cholesterol in adults without cardiovascular disease: The Interactive Cholesterol Advisory Tool.

PubMed

Block, Robert C; Abdolahi, Amir; Niemiec, Christopher P; Rigby, C Scott; Williams, Geoffrey C

2016-12-01

There is a lack of research on the use of electronic tools that guide patients toward reducing their cardiovascular disease risk. We conducted a 9-month clinical trial in which participants who were at low (n = 100) and moderate (n = 23) cardiovascular disease risk-based on the National Cholesterol Education Program III's 10-year risk estimator-were randomized to usual care or to usual care plus use of an Interactive Cholesterol Advisory Tool during the first 8 weeks of the study. In the moderate-risk category, an interaction between treatment condition and Framingham risk estimate on low-density lipoprotein and non-high-density lipoprotein cholesterol was observed, such that participants in the virtual clinician treatment condition had a larger reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol as their Framingham risk estimate increased. Perceptions of the Interactive Cholesterol Advisory Tool were positive. Evidence-based information about cardiovascular disease risk and its management was accessible to participants without major technical challenges. © The Author(s) 2015.

Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins.

PubMed

Karimi, Nasibeh; Cvjetkovic, Aleksander; Jang, Su Chul; Crescitelli, Rossella; Hosseinpour Feizi, Mohammad Ali; Nieuwland, Rienk; Lötvall, Jan; Lässer, Cecilia

2018-02-13

The isolation of extracellular vesicles (EVs) from blood is of great importance to understand the biological role of circulating EVs and to develop EVs as biomarkers of disease. Due to the concurrent presence of lipoprotein particles, however, blood is one of the most difficult body fluids to isolate EVs from. The aim of this study was to develop a robust method to isolate and characterise EVs from blood with minimal contamination by plasma proteins and lipoprotein particles. Plasma and serum were collected from healthy subjects, and EVs were isolated by size-exclusion chromatography (SEC), with most particles being present in fractions 8-12, while the bulk of the plasma proteins was present in fractions 11-28. Vesicle markers peaked in fractions 7-11; however, the same fractions also contained lipoprotein particles. The purity of EVs was improved by combining a density cushion with SEC to further separate lipoprotein particles from the vesicles, which reduced the contamination of lipoprotein particles by 100-fold. Using this novel isolation procedure, a total of 1187 proteins were identified in plasma EVs by mass spectrometry, of which several proteins are known as EV-associated proteins but have hitherto not been identified in the previous proteomic studies of plasma EVs. This study shows that SEC alone is unable to completely separate plasma EVs from lipoprotein particles. However, combining SEC with a density cushion significantly improved the separation of EVs from lipoproteins and allowed for a detailed analysis of the proteome of plasma EVs, thus making blood a viable source for EV biomarker discovery.

Cholesterol values in free-ranging gorillas (Gorilla gorilla gorilla and Gorilla beringei) and Bornean orangutans (Pongo pygmaeus).

PubMed

Schmidt, Debra A; Ellersieck, Mark R; Cranfield, Michael R; Karesh, William B

2006-09-01

Cholesterol concentrations in captive gorillas and orangutans vary widely within species and average approximately 244 mg/dl for gorillas and 169 mg/dl for orangutans as published previously. The International Species Inventory System reports higher concentrations of 275 and 199 mg/dl for gorillas and orangutans, respectively. It is unknown whether these values were typical, influenced by captive management, or both. To answer this question, banked serum samples from free-ranging mountain gorillas (Gorilla beringei), western lowland gorillas (Gorilla gorilla gorilla), and Bornean orangutans (Pongo pygmaeus) were analyzed for total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations. Mountain gorillas did not differ significantly from free-ranging western lowland gorillas in cholesterol, triglyceride, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol concentrations, indicating mountain gorilla values could be a model for western lowland gorillas. Captive gorilla total cholesterol and low-density lipoprotein cholesterol concentrations were significantly higher (P < 0.05) than in free-ranging groups. Triglyceride concentrations for captive gorillas were significantly higher (P < 0.05) than the male mountain and western lowland gorillas, but they were not significantly different from the female mountain gorillas. Captive orangutan total cholesterol concentrations were only higher (P < 0.05) than the free-ranging female orangutans, whereas captive orangutan low-density lipoprotein cholesterol concentrations were significantly higher (P < 0.05) than both free-ranging male and female orangutans. Calculated and measured low-density lipoprotein cholesterol concentrations were compared for all free-ranging animals and were significantly different (P < 0.05) for all groups, indicating Friedewald's equation for calculating low-density lipoprotein cholesterol is not appropriate for use with nonfasted apes. The higher total cholesterol and low-density lipoprotein cholesterol concentrations in captive apes may predispose them to cardiovascular disease and might be attributed to diets, limited energy expenditure, and genetics.

Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase-Independent Effects.

PubMed

Drenos, Fotios; Davey Smith, George; Ala-Korpela, Mika; Kettunen, Johannes; Würtz, Peter; Soininen, Pasi; Kangas, Antti J; Dale, Caroline; Lawlor, Debbie A; Gaunt, Tom R; Casas, Juan-Pablo; Timpson, Nicholas J

2016-06-01

Plasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low-density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease. We aimed to characterize the impact of this locus across a broad set of mainly lipids-focused metabolic measures. A high-throughput serum nuclear magnetic resonance metabolomics platform was used to quantify 225 metabolic measures in 13 285 participants from 2 European population cohorts. We analyzed the effect of the APOC3 variant on the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent effects. Eighty-one metabolic measures showed evidence of association with APOC3(rs138326449). In addition to previously reported triglyceride and high-density lipoprotein associations, the variant was also associated with very low-density lipoprotein and high-density lipoprotein composition measures, other cholesterol measures, and fatty acids. Comparison of the APOC3 and LPL associations revealed that APOC3 association results for medium and very large very low-density lipoprotein composition are unlikely to be solely predictable by the action of APOC3 through LPL. We characterized the effects of the rare APOC3(rs138326449) loss of function mutation in lipoprotein metabolism, as well as the effects of LPL(rs12678919). Our results improve our understanding of the role of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated nature of human metabolites. © 2016 The Authors.

Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase–Independent Effects

PubMed Central

Davey Smith, George; Ala-Korpela, Mika; Kettunen, Johannes; Würtz, Peter; Soininen, Pasi; Kangas, Antti J.; Dale, Caroline; Lawlor, Debbie A.; Gaunt, Tom R.; Casas, Juan-Pablo

2016-01-01

Background— Plasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low–density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease. We aimed to characterize the impact of this locus across a broad set of mainly lipids-focused metabolic measures. Methods and Results— A high-throughput serum nuclear magnetic resonance metabolomics platform was used to quantify 225 metabolic measures in 13 285 participants from 2 European population cohorts. We analyzed the effect of the APOC3 variant on the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent effects. Eighty-one metabolic measures showed evidence of association with APOC3(rs138326449). In addition to previously reported triglyceride and high-density lipoprotein associations, the variant was also associated with very low–density lipoprotein and high-density lipoprotein composition measures, other cholesterol measures, and fatty acids. Comparison of the APOC3 and LPL associations revealed that APOC3 association results for medium and very large very low–density lipoprotein composition are unlikely to be solely predictable by the action of APOC3 through LPL. Conclusions— We characterized the effects of the rare APOC3(rs138326449) loss of function mutation in lipoprotein metabolism, as well as the effects of LPL(rs12678919). Our results improve our understanding of the role of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated nature of human metabolites. PMID:27114411

Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies.

PubMed Central

Clarke, R.; Frost, C.; Collins, R.; Appleby, P.; Peto, R.

1997-01-01

OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol. PMID:9006469

Low-density lipoprotein reconstituted by pyropheophorbide cholesteryl oleate as target-specific photosensitizer.

PubMed

Zheng, Gang; Li, Hui; Zhang, Min; Lund-Katz, Sissel; Chance, Britton; Glickson, Jerry D

2002-01-01

To target tumors overexpressing low-density lipoprotein receptors (LDLr), a pyropheophorbide cholesterol oleate conjugate was synthesized and successfully reconstituted into the low-density lipoprotein (LDL) lipid core. Laser scanning confocal microscopy studies demonstrated that this photosensitizer-reconstituted LDL can be internalized via LDLr by human hepatoblastoma G(2) (HepG(2)) tumor cells.

Fitness, Heart Disease, and High-Density Lipoproteins: A Look at the Relationships.

ERIC Educational Resources Information Center

McCunney, Robert J.

1987-01-01

The role of fitness in preventing coronary heart disease is explored. Research on high-density lipoprotein, which has been found to be one of the most critical determinants of risk, is reviewed. The relationship between fitness, high-density lipoprotein, and coronary heart disease is assessed, and clinical implications are spelled out. (MT)

New insights into the pathophysiology of dyslipidemia in type 2 diabetes.

PubMed

Taskinen, Marja-Riitta; Borén, Jan

2015-04-01

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for patients with type 2 diabetes, despite recent significant advances in management strategies to lessen CVD risk factors. A major cause is the atherogenic dyslipidemia, which consists of elevated plasma concentrations of both fasting and postprandial triglyceride-rich lipoproteins (TRLs), small dense low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) cholesterol. The different components of diabetic dyslipidemia are not isolated abnormalities but closely linked to each other metabolically. The underlying disturbances are hepatic overproduction and delayed clearance of TRLs. Recent results have unequivocally shown that triglyceride-rich lipoproteins and their remnants are atherogenic. To develop novel strategies for the prevention and treatment of dyslipidaemia, it is essential to understand the pathophysiology of dyslipoproteinaemia in humans. Here, we review recent advances in our understanding of the pathophysiology of diabetic dyslipidemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

New Frontiers in the Treatment of Diabetic Dyslipidemia

PubMed Central

Wang, Shu-Yi; Hsieh, Ming-Chia; Tu, Shih-Te; Chuang, Chieh-Sen

2013-01-01

Dyslipidemia is a major risk factor for cardiovascular complications in people with diabetes. Lowering low-density lipoprotein cholesterol (LDL-C) levels is effective in the primary and secondary prevention of diabetic vascular complications. However, LDL-C levels do not reflect all aspects of diabetic dyslipidemia, which is characterized by hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). Statins, nicotinic acid, and fibrates play a role in treating diabetic dyslipidemia. Atherosclerosis is a major disorder of the blood vessel wall in patients with diabetes. A number of antihyperlipidemic agents may be beneficial and exhibit effects at the actual site of vascular disease and not only on plasma lipoprotein concentrations. Several novel therapeutic compounds are currently being developed. These include additional therapeutics for LDL-C, triglycerides, HDL-C, and modulators of inflammation that can be used as possible synergic agents for the treatment of atherosclerosis and irregularities in plasma lipoprotein concentrations. PMID:24380093

Plasma lipoprotein and apolipoprotein distribution as a function of density in the rainbow trout (Salmo gairdneri).

PubMed Central

Babin, P J

1987-01-01

I have previously described [Babin (1987) J. Biol. Chem. 262, 4290-4296] the apolipoprotein composition of the major classes of trout plasma lipoproteins. The present work describes the use of an isopycnic density gradient centrifugation procedure and sequential flotation ultracentrifugation to show: (1) the presence of intermediate density lipoproteins (IDL) in the plasma, between 1.015 and 1.040 g/ml; (2) the existence of a single type of Mr 240,000 apoB-like in the low density lipoproteins (LDL, 1.040 less than p less than 1.085 g/ml); (3) the presence of apoA-I-like (Mr 25,000) in the densest LDL; (4) the adequacy of 1.085 g/ml as a cutoff between the LDL and high density lipoproteins (HDL); (5) the accumulation of Mr 55,000 and 76,000 apolipoproteins and apoA-like apolipoproteins in the 1.21 g/ml infranatant. The fractionation of trout lipoprotein spectrum thus furnishes the distribution of the different lipoprotein classes and leads to the description of the constituent apolipoproteins, which account for about 36% of circulating plasma proteins in this species. Images Fig. 2. Fig. 3. PMID:3689318

The triglyceride to high-density lipoprotein-cholesterol ratio in adolescence and subsequent weight gain predict nuclear magnetic resonance-measured lipoprotein subclasses in adulthood.

PubMed

Weiss, Ram; Otvos, James D; Sinnreich, Ronit; Miserez, Andre R; Kark, Jeremy D

2011-01-01

To assess whether the fasting triglyceride-to-high-density lipoprotein (HDL)-cholesterol (TG/HDL) ratio in adolescence is predictive of a proatherogenic lipid profile in adulthood. A longitudinal follow-up of 770 Israeli adolescents 16 to 17 years of age who participated in the Jerusalem Lipid Research Clinic study and were reevaluated 13 years later. Lipoprotein particle size was assessed at the follow-up with proton nuclear magnetic resonance. The TG/HDL ratio measured in adolescence was strongly associated with low-density lipoprotein, very low-density lipoprotein (VLDL), and HDL mean particle size in young adulthood in both sexes, even after adjustment for baseline body mass index and body mass index change. The TG/HDL ratio measured in adolescence and subsequent weight gain independently predicted atherogenic small low-density lipoprotein and large VLDL particle concentrations (P < .001 in both sexes). Baseline TG/HDL and weight gain interacted to increase large VLDL concentration in men (P < .001). Adolescents with an elevated TG/HDL ratio are prone to express a proatherogenic lipid profile in adulthood. This profile is additionally worsened by weight gain. Copyright © 2011 Mosby, Inc. All rights reserved.

Variants for HDL-C, LDL-C, and triglycerides identified from admixture mapping and fine-mapping analysis in African American families.

PubMed

Shetty, Priya B; Tang, Hua; Feng, Tao; Tayo, Bamidele; Morrison, Alanna C; Kardia, Sharon L R; Hanis, Craig L; Arnett, Donna K; Hunt, Steven C; Boerwinkle, Eric; Rao, Dabeeru C; Cooper, Richard S; Risch, Neil; Zhu, Xiaofeng

2015-02-01

Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African Americans. The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. The analysis was performed in 1905 unrelated African American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program (FBPP). Regions showing admixture evidence were followed-up with family-based association analysis in 3556 African American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body mass index, and genome-wide mean ancestry to minimize the confounding caused by population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (low-density lipoprotein cholesterol), 8 (high-density lipoprotein cholesterol), 14 (triglycerides), and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52 939 single-nucleotide polymorphisms (SNPs) were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with high-density lipoprotein cholesterol (2 SNPs), low-density lipoprotein cholesterol (4 SNPs), and triglycerides (5 SNPs). The family data were used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions, including genes with known associations for cardiovascular disease. This study identified regions on chromosomes 7, 8, 14, and 19 and 11 SNPs from the fine-mapping analysis that were associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides for further studies of cardiovascular disease in African Americans. © 2014 American Heart Association, Inc.

Relation of Cholesterol and Lipoprotein Parameters with Carotid Artery Plaque Characteristics: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study

PubMed Central

Virani, Salim S.; Catellier, Diane J.; Pompeii, Lisa A.; Nambi, Vijay; Hoogeveen, Ron C.; Wasserman, Bruce A.; Coresh, Josef; Mosley, Thomas H.; Otvos, James D.; Sharrett, A. Richey; Boerwinkle, Eric; Ballantyne, Christie M.

2011-01-01

Objective There is a paucity of data regarding relations of apolipoproteins (apolipoprotein B [ApoB] and apolipoprotein A-1 [Apo A-1]), lipoprotein particle measures (low-density lipoprotein particle concentration [LDLp] and high-density lipoprotein particle concentration [HDLp]), and lipoprotein cholesterol measures (low-density lipoprotein cholesterol [LDL-C], non–high-density lipoprotein cholesterol [non– HDL-C], and high-density lipoprotein cholesterol [HDL-C]) with atherosclerotic plaque burden, plaque eccentricity, and lipid-rich core presence as a marker of high-risk plaques. Methods Carotid artery magnetic resonance imaging was performed in 1,670 Atherosclerosis Risk in Communities study participants. Vessel wall and lipid cores were measured; normalized wall index (NWI), standard deviation (SD) of wall thickness (measure of plaque eccentricity) were calculated; and lipid cores were detected in vessels with ≥1.5 mm thickness. Fasting concentrations of cholesterol, ApoB and Apo A-1, and LDLp and HDLp were measured. Results Measures of plaque burden (carotid wall volume, wall thickness, and NWI) were positively associated with atherogenic cholesterol and lipoproteins (p<0.05 for total cholesterol, LDL-C, non–HDL-C, ApoB, and LDLp), but not with HDL-C, Apo A-1, or HDLp. SD of wall thickness was associated with total cholesterol (p 0.01) and non-HDL-C (p 0.02). Although measures of atherogenic or anti-atherogenic cholesterol or lipoprotein were not individually associated with detection of a lipid-rich core, their ratios (total cholesterol/HDL-C, non–HDL-C/ HDL-C, and LDLp/HDLp) were associated with lipid-rich core presence (p≤0.05). Conclusion Extent of carotid atherosclerosis is associated with atherogenic cholesterol and lipoproteins. Atherogenic/anti-atherogenic cholesterol or particle ratios were associated with presence of a detectable lipid-rich core. PMID:21868017

Relation of cholesterol and lipoprotein parameters with carotid artery plaque characteristics: the Atherosclerosis Risk in Communities (ARIC) carotid MRI study.

PubMed

Virani, Salim S; Catellier, Diane J; Pompeii, Lisa A; Nambi, Vijay; Hoogeveen, Ron C; Wasserman, Bruce A; Coresh, Josef; Mosley, Thomas H; Otvos, James D; Sharrett, A Richey; Boerwinkle, Eric; Ballantyne, Christie M

2011-12-01

There is a paucity of data regarding relations of apolipoproteins (apolipoprotein B [ApoB] and apolipoprotein A-1 [Apo A-1]), lipoprotein particle measures (low-density lipoprotein particle concentration [LDLp] and high-density lipoprotein particle concentration [HDLp]), and lipoprotein cholesterol measures (low-density lipoprotein cholesterol [LDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], and high-density lipoprotein cholesterol [HDL-C]) with atherosclerotic plaque burden, plaque eccentricity, and lipid-rich core presence as a marker of high-risk plaques. Carotid artery magnetic resonance imaging was performed in 1670 Atherosclerosis Risk in Communities study participants. Vessel wall and lipid cores were measured; normalized wall index (NWI), standard deviation (SD) of wall thickness (measure of plaque eccentricity) were calculated; and lipid cores were detected in vessels with ≥ 1.5mm thickness. Fasting concentrations of cholesterol, ApoB and Apo A-1, and LDLp and HDLp were measured. Measures of plaque burden (carotid wall volume, wall thickness, and NWI) were positively associated with atherogenic cholesterol and lipoproteins (p < 0.05 for total cholesterol, LDL-C, non-HDL-C, ApoB, and LDLp), but not with HDL-C, Apo A-1, or HDLp. SD of wall thickness was associated with total cholesterol (p 0.01) and non-HDL-C (p 0.02). Although measures of atherogenic or anti-atherogenic cholesterol or lipoprotein were not individually associated with detection of a lipid-rich core, their ratios (total cholesterol/HDL-C, non-HDL-C/HDL-C, and LDLp/HDLp) were associated with lipid-rich core presence (p ≤ 0.05). Extent of carotid atherosclerosis is associated with atherogenic cholesterol and lipoproteins. Atherogenic/anti-atherogenic cholesterol or particle ratios were associated with presence of a detectable lipid-rich core. Published by Elsevier Ireland Ltd.

Insulin resistance in obesity as the underlying cause for the metabolic syndrome.

PubMed

Gallagher, Emily J; Leroith, Derek; Karnieli, Eddy

2010-01-01

The metabolic syndrome affects more than a third of the US population, predisposing to the development of type 2 diabetes and cardiovascular disease. The 2009 consensus statement from the International Diabetes Federation, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, and the National Heart, Lung, and Blood Institute defines the metabolic syndrome as 3 of the following elements: abdominal obesity, elevated blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia. Many factors contribute to this syndrome, including decreased physical activity, genetic predisposition, chronic inflammation, free fatty acids, and mitochondrial dysfunction. Insulin resistance appears to be the common link between these elements, obesity and the metabolic syndrome. In normal circumstances, insulin stimulates glucose uptake into skeletal muscle, inhibits hepatic gluconeogenesis, and decreases adipose-tissue lipolysis and hepatic production of very-low-density lipoproteins. Insulin signaling in the brain decreases appetite and prevents glucose production by the liver through neuronal signals from the hypothalamus. Insulin resistance, in contrast, leads to the release of free fatty acids from adipose tissue, increased hepatic production of very-low-density lipoproteins and decreased high-density lipoproteins. Increased production of free fatty acids, inflammatory cytokines, and adipokines and mitochondrial dysfunction contribute to impaired insulin signaling, decreased skeletal muscle glucose uptake, increased hepatic gluconeogenesis, and β cell dysfunction, leading to hyperglycemia. In addition, insulin resistance leads to the development of hypertension by impairing vasodilation induced by nitric oxide. In this review, we discuss normal insulin signaling and the mechanisms by which insulin resistance contributes to the development of the metabolic syndrome.

Lipoprotein-Cholesterol Fractions in Marginalized Roma versus Majority Population.

PubMed

Hubková, Beáta; Bódy, Gabriel; Mašlanková, Jana; Birková, Anna; Frišman, Eugen; Kraus, Vladimír; Mareková, Mária

2018-01-06

The trend of modern clinical biochemistry is to emphasize the composition and the quality of lipoproteins over their quantity. The serum lipoprotein fractions and subfractions were analyzed by the Lipoprint Lipoprotein Subfractions Testing System, the parameters of lipid profile, as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triacylglycerides (TAG) were determined by an automated selective biochemical analyzer. Our results showed a significantly lower concentration of cholesterol in the LDL fractions 1 and 2 and in the HDL fractions 8 to 10 in Roma compared to the majority population. The most significant differences between Roma and the majority population when considering body mass index (BMI), waist-to-hip ratio and the index of central obesity were in very low-density lipoproteins (VLDL), intermediate-density lipoproteins, fraction A (IDL-A) and LDL-2. The last two listed were significantly higher in the majority population. VLDL was significantly higher in overweight or obese Roma men and in Roma men with central obesity compared to men from the majority population, as well as in Roma women with normal weight and physiological waist-to-hip ratio compared to the women from majority population. Our study is among the first describing the distribution of lipoprotein subfractions in different ethnic groups.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

PubMed

Maki, K C; Lawless, A L; Kelley, K M; Kaden, V N; Geiger, C J; Palacios, O M; Dicklin, M R

2017-01-01

Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL 1+2 -C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6  versus 0.7 mg/dl, respectively, P=0.016). CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.

Expression of lipoprotein receptor and apolipoprotein E genes by perinatal rat lipid-laden pulmonary fibroblasts.

PubMed

McGowan, S E; Doro, M M; Jackson, S

Lipid-laden interstitial fibroblasts (LIFs) are abundant during alveolar septal formation in rats and accumulate droplets of neutral lipids. The mechanisms controlling lipid acquisition by LIFs are incompletely understood and accumulation varies during postnatal development, because lipid droplets are usually a transient phenotype. We hypothesized that plasma lipoproteins may be an important source of lipids and that the cells may alter their acquisition of lipoproteins by changing the expression of lipoprotein receptors and apolipoprotein E. We quantified the accumulation low-density lipoproteins (LDLs) and very-low-density lipoproteins (VLDLs) by LIFs and the expression of LDL and VLDL receptors mRNA and protein at various perinatal ages and found no significant age-related differences. Apolipoprotein E mRNA was maximal at postnatal day 15, whereas immunoreactive apolipoprotein E protein was maximal at gestational day 21, suggesting complex regulation. Our findings indicate that the age-related difference in the lipid droplet contents of LIFs is not primarily related to differences in LDL or VLDL receptor expression. They suggest that changes in the quantities of plasma lipoproteins, which are presented to LIFs in the lung at various perinatal ages, are more likely to be responsible for age-related alterations in lipid droplet size and abundance.

A Randomized Study Comparing the Effects of a Low-Carbohydrate Diet and a Conventional Diet on Lipoprotein Subfractions and C-reactive Protein Levels in Patients With Severe Obesity.

PubMed

Moretti, Laura; Canada, Todd

2006-04-01

To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months. Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference =-0.26 mg/dL, p = .03) but more frequently developed detectable chylomicrons (44% vs 22%, p = .04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = -30 nmol/L, p = .74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, p = .63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = -2 mg/dL, p = .005), independent of weight loss. In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions. ( Am J Med. 2004;117:398-405.).

A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity.

PubMed

Seshadri, Prakash; Iqbal, Nayyar; Stern, Linda; Williams, Monica; Chicano, Kathryn L; Daily, Denise A; McGrory, Joyce; Gracely, Edward J; Rader, Daniel J; Samaha, Frederick F

2004-09-15

To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months. Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = -0.26 mg/dL, P = 0.03) but more frequently developed detectable chylomicrons (44% vs. 22%, P = 0.04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = -30 nmol/L, P = 0.74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, P = 0.63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n = 48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference = -2.0 mg/dL, P = 0.005), independent of weight loss. In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions. Copyright 2004 Elsevier Inc.

Lipid Panel Reference Intervals for Amazon Parrots (Amazona species).

PubMed

Ravich, Michelle; Cray, Carolyn; Hess, Laurie; Arheart, Kristopher L

2014-09-01

The lipoprotein panel is a useful diagnostic tool that allows clinicians to evaluate blood lipoprotein fractions. It is a standard diagnostic test in human medicine but is poorly understood in avian medicine. Amazon parrots (Amazona species) are popular pets that frequently lead a sedentary lifestyle and are customarily fed high-fat diets. Similar to people with comparable diets and lifestyles, Amazon parrots are prone to obesity and atherosclerosis. In human medicine, these conditions are typically correlated with abnormalities in the lipoprotein panel. To establish reference intervals for the lipoprotein panel in Amazon parrots, plasma samples from 31 captive Amazon parrots were analyzed for concentrations of cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL). The data were also grouped according to sex, diet, body condition score, and age. Aside from HDL levels, which were significantly different between male and female parrots, no intergroup differences were found for any of the lipoprotein fractions.

Developing Optimized Treatment Plans for Patients with Dyslipidemia in the Era of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapeutics.

PubMed

Underberg, James A; Blaha, Michael J; Jackson, Elizabeth J; Jones, Peter H

2017-10-01

This educational content was derived from a live satellite symposium at the American College of Physicians Internal Medicine Meeting 2017 in San Diego, California (online at http://courses.elseviercme.com/acp/702e). This activity will focus on optimized treatment plans for patients with dyslipidemia in the era of proprotein convertase subtilisin/kexin type 9 inhibitor therapeutics. Low-density lipoprotein cholesterol has been identified as an important therapeutic target to prevent the progression of atherosclerotic disease; however, only 1 of every 3 adults with high low-density lipoprotein cholesterol has the condition under control. Expert faculty on this panel will discuss the science of proprotein convertase subtilisin/kexin type 9 inhibitors and aid physicians in the best practices to achieve low-density lipoprotein cholesterol target in their patients. Copyright © 2017. Published by Elsevier Inc.

Cholesterol Metabolism in CKD

PubMed Central

Reiss, Allison B.; Voloshyna, Iryna; DeLeon, Joshua; Miyawaki, Nobuyuki; Mattana, Joseph

2015-01-01

Patients with chronic kidney disease (CKD) have a substantial risk of developing coronary artery disease. Traditional cardiovascular disease (CVD) risk factors such as hypertension and hyperlipidemia do not adequately explain the high prevalence of CVD in CKD. Both CVD and CKD are inflammatory states and inflammation adversely impacts lipid balance. Dyslipidemia in CKD is characterized by elevated triglycerides and high density lipoprotein that is both decreased and dysfunctional. This dysfunctional high density lipoprotein becomes pro-inflammatory and loses its atheroprotective ability to promote cholesterol efflux from cells, including lipid-overloaded macrophages in the arterial wall. Elevated triglycerides result primarily from defective clearance. The weak association between low density lipoprotein cholesterol level and coronary risk in CKD has led to controversy over the usefulness of statin therapy. This review examines disrupted cholesterol transport in CKD, presenting both clinical and pre-clinical evidence of the impact of the uremic environment on vascular lipid accumulation. Preventative and treatment strategies are explored. PMID:26337134

Effects of Diet High in Palmitoleic Acid on Serum Lipid Levels and Metabolism

DTIC Science & Technology

2000-07-01

cholesterol , high - density a typical American diet. lipoprotein cholesterol , and triglyceride ...group imbalance resulting from density lipoprotein ( HDL ) cholesterol , and triglyceride dropouts or exclusions during the run-in or early in the levels...Circulation 1997;95:69-75. 15. Austin MA, Rodriguez BL, McKnight B, JD Curb. Low- density lipoprotein (LDL) particle size and plasma triglyceride ( TG

Distribution of thiobarbituric acid-reactive substances in lipoproteins and proteins in serum.

PubMed

Bonnefont, D; Legrand, A; Peynet, J; Emerit, J; Delattre, J; Galli, A

1989-10-01

We assessed the distribution of malondialdehyde (MDA) in lipoproteins and proteins in serum after using two procedures to separate the lipoproteins: sequential ultracentrifugation or selective precipitation with a sodium phosphotungstate and magnesium chloride reagent followed by ultracentrifugation of the supernate. MDA concentrations were determined by the thiobarbituric acid reaction and quantified by fluorometry. We found that 43% of the thiobarbituric acid-reactive substances (TBARS) was bound to the lipoproteins--27% to very-low- and low-density lipoproteins (VLDL-LDL) and 16% to high-density lipoproteins (HDL)--and from 11.5% to 15.8% to proteins, depending on the separation procedure. Residual unbound TBARS were located in the ultracentrifugation layers that contained no lipoproteins or proteins. The TBARS concentration in serum lipoproteins containing apolipoprotein B (i.e., VLDL-LDL) was the same after ultracentrifugation or selective precipitation. We therefore consider the precipitation method more suitable for routine TBARS determination in these lipoproteins, because it is easier to handle and faster. However, for determination of TBARS in HDL, selective precipitation requires subsequent ultracentrifugation at a density of 1.21 kg/L.

Novel lipoprotein density profiling in healthy dogs of various breeds, healthy miniature schnauzers, and miniature schnauzers with hyperlipidemia

PubMed Central

2013-01-01

Background Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. Results The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. Conclusions The results of the present study suggest that density gradient ultracentrifugation using NaBiEDTA is a useful screening method for the study of lipoprotein profiles in dogs. Therefore, this method could potentially be used for diagnostic purposes for the separation of dogs suspected of having lipoprotein abnormalities from healthy dogs. PMID:23497598

Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lichtenstein, A.H.; Cohn, J.S.; Hachey, D.L.

1990-09-01

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of (5,5,5,-2H3)leucine, (4,4,4,-2H3)valine, and (6,6-2H2,1,2-13C2)lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine)more » mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine), and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.« less

Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits.

PubMed Central

Keaney, J F; Gaziano, J M; Xu, A; Frei, B; Curran-Celentano, J; Shwaery, G T; Loscalzo, J; Vita, J A

1993-01-01

Recent evidence suggests that dietary therapy with lipid-soluble antioxidants may be beneficial for patients with atherosclerotic vascular disease but the potential mechanism(s) for these observations remain obscure. Abnormalities in endothelium-dependent control of vascular tone develop early in the course of atherosclerosis and may result from oxidative modification of low density lipoproteins. We examined the role of dietary antioxidants in preserving normal endothelial cell vasodilator function in cholesterol-fed rabbits with particular attention to possible effects on serum lipoproteins, low density lipoprotein oxidation, and atherogenesis. Male New Zealand White rabbits were fed diets containing no additive (controls), 1% cholesterol (cholesterol group), or 1% cholesterol chow supplemented with either beta-carotene (0.6 g/kg of chow) or alpha-tocopherol (1000 international units/kg of chow) for a 28-day period. After dietary therapy, thoracic aortae were harvested for assay of vascular function and for pathologic examination and tissue antioxidant levels. Compared to controls, acetylcholine- and A23187-mediated endothelium-dependent relaxations were significantly impaired in vessels from the cholesterol group (P < 0.001), whereas vessels from animals treated with beta-carotene or alpha-tocopherol demonstrated normal endothelium-dependent arterial relaxation. Preservation of endothelial function was associated with vascular incorporation of alpha-tocopherol and beta-carotene but was unrelated to plasma lipoprotein levels, smooth muscle cell function, or the extent of atherosclerosis. Increased low density lipoprotein resistance to ex vivo copper-mediated oxidation was observed only in the alpha-tocopherol group. Our results suggest that dietary antioxidants may benefit patients with atherosclerosis by preserving endothelial vasodilator function through a mechanism related to vascular tissue antioxidant content and not reflected by assay of low density lipoprotein resistance to ex vivo oxidation. PMID:8265642

High density lipoproteins: Measurement techniques and potential biomarkers of cardiovascular risk

PubMed Central

Hafiane, Anouar; Genest, Jacques

2015-01-01

Plasma high density lipoprotein cholesterol (HDL) comprises a heterogeneous family of lipoprotein species, differing in surface charge, size and lipid and protein compositions. While HDL cholesterol (C) mass is a strong, graded and coherent biomarker of cardiovascular risk, genetic and clinical trial data suggest that the simple measurement of HDL-C may not be causal in preventing atherosclerosis nor reflect HDL functionality. Indeed, the measurement of HDL-C may be a biomarker of cardiovascular health. To assess the issue of HDL function as a potential therapeutic target, robust and simple analytical methods are required. The complex pleiotropic effects of HDL make the development of a single measurement challenging. Development of laboratory assays that accurately HDL function must be developed validated and brought to high-throughput for clinical purposes. This review discusses the limitations of current laboratory technologies for methods that separate and quantify HDL and potential application to predict CVD, with an emphasis on emergent approaches as potential biomarkers in clinical practice. PMID:26674734

Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy

PubMed Central

Stein, James H.; Komarow, Lauren; Cotter, Bruno R.; Currier, Judith S.; Dubé, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Parker, Robert A.; Torriani, Francesca J.

2008-01-01

Background Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. Objective To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. Methods This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. Results Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (pKW<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (pKW=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. Conclusions Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir. PMID:19956354

NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells.

PubMed

She, Zhi-Gang; Chang, Yunchao; Pang, Hong-Bo; Han, Wenlong; Chen, Hou-Zao; Smith, Jeffrey W; Stallcup, William B

2016-01-01

Obesity and hyperlipidemia are critical risk factors for atherosclerosis. Because ablation of NG2 proteoglycan in mice leads to hyperlipidemia and obesity, we investigated the impact of NG2 ablation on atherosclerosis in apoE null mice. Immunostaining indicates that NG2 expression in plaque, primarily by synthetic smooth muscle cells, increases during atherogenesis. NG2 ablation unexpectedly results in decreased (30%) plaque development, despite aggravated obesity and hyperlipidemia. Mechanistic studies reveal that NG2-positive plaque synthetic smooth muscle cells in culture can sequester low-density lipoprotein to enhance foam-cell formation, processes in which NG2 itself plays direct roles. In agreement with these observations, low-density lipoprotein retention and lipid accumulation in the NG2/ApoE knockout aorta is 30% less than that seen in the control aorta. These results indicate that synthetic smooth muscle cell-dependent low-density lipoprotein retention and foam cell formation outweigh obesity and hyperlipidemia in promoting mouse atherogenesis. Our study sheds new light on the role of synthetic smooth muscle cells during atherogenesis. Blocking plaque NG2 or altering synthetic smooth muscle cells function may be promising therapeutic strategies for atherosclerosis. © 2015 American Heart Association, Inc.

A clustering analysis of lipoprotein diameters in the metabolic syndrome

USDA-ARS?s Scientific Manuscript database

The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

Effect of n-3 polyunsaturated fatty acids on the lipidic profile of healthy Mexican volunteers.

PubMed

Carvajal, O; Angulo, O

1997-01-01

The effect of n-3 polyunsaturated fatty acids on the serum lipid profile in a Mexican population was evaluated. Three g of salmon oil was the daily intake during four weeks. Total cholesterol, triglycerides, low density lipoproteins, high density lipoproteins and erythrocyte fatty acid composition were analyzed. The hypertriglyceridemic group showed a statistically significant (p < 0.05) reduction of triglycerides and significant (p < 0.01) elevation of high density lipoproteins. The hypercholesterolemic group reduced significantly the levels of cholesterol and triglycerides; high density lipoproteins were augmented by 11.6%. The hypolipidemic effect of n-3 polyunsaturated fatty acids was manifest in the Mexican volunteers under the conditions here evaluated.

The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury.

PubMed

Alavi, M Z; Richardson, M; Moore, S

1989-02-01

The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel-exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low-density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions.

Familial hypercholesterolemia

MedlinePlus

Type II hyperlipoproteinemia; Hypercholesterolemic xanthomatosis; Low density lipoprotein receptor mutation ... defect makes the body unable to remove low density lipoprotein (LDL, or bad) cholesterol from the blood. ...

Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries.

PubMed

Sacks, Frank M; Hermans, Michel P; Fioretto, Paola; Valensi, Paul; Davis, Timothy; Horton, Edward; Wanner, Christoph; Al-Rubeaan, Khalid; Aronson, Ronnie; Barzon, Isabella; Bishop, Louise; Bonora, Enzo; Bunnag, Pongamorn; Chuang, Lee-Ming; Deerochanawong, Chaicharn; Goldenberg, Ronald; Harshfield, Benjamin; Hernández, Cristina; Herzlinger-Botein, Susan; Itoh, Hiroshi; Jia, Weiping; Jiang, Yi-Der; Kadowaki, Takashi; Laranjo, Nancy; Leiter, Lawrence; Miwa, Takashi; Odawara, Masato; Ohashi, Ken; Ohno, Atsushi; Pan, Changyu; Pan, Jiemin; Pedro-Botet, Juan; Reiner, Zeljko; Rotella, Carlo Maria; Simo, Rafael; Tanaka, Masami; Tedeschi-Reiner, Eugenia; Twum-Barima, David; Zoppini, Giacomo; Carey, Vincent J

2014-03-04

Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Effects of Vegetarian Diets on Blood Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Wang, Fenglei; Zheng, Jusheng; Yang, Bo; Jiang, Jiajing; Fu, Yuanqing; Li, Duo

2015-10-27

Vegetarian diets exclude all animal flesh and are being widely adopted by an increasing number of people; however, effects on blood lipid concentrations remain unclear. This meta-analysis aimed to quantitatively assess the overall effects of vegetarian diets on blood lipids. We searched PubMed, Scopus, Embase, ISI Web of Knowledge, and the Cochrane Library through March 2015. Studies were included if they described the effectiveness of vegetarian diets on blood lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride). Weighted mean effect sizes were calculated for net changes by using a random-effects model. We performed subgroup and univariate meta-regression analyses to explore sources of heterogeneity. Eleven trials were included in the meta-analysis. Vegetarian diets significantly lowered blood concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and the pooled estimated changes were -0.36 mmol/L (95% CI -0.55 to -0.17; P<0.001), -0.34 mmol/L (95% CI -0.57 to -0.11; P<0.001), -0.10 mmol/L (95% CI -0.14 to -0.06; P<0.001), and -0.30 mmol/L (95% CI -0.50 to -0.10; P=0.04), respectively. Vegetarian diets did not significantly affect blood triglyceride concentrations, with a pooled estimated mean difference of 0.04 mmol/L (95% CI -0.05 to 0.13; P=0.40). This systematic review and meta-analysis provides evidence that vegetarian diets effectively lower blood concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. Such diets could be a useful nonpharmaceutical means of managing dyslipidemia, especially hypercholesterolemia. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Lipid and lipoprotein testing in resource-limited laboratories.

PubMed

Myers, Gary L

2003-01-01

The role of total cholesterol (TC) and lipoproteins in the assessment of coronary heart disease (CHD) is firmly established from population and intervention studies. Total and low-density lipoprotein cholesterol (LDLC) levels are positively associated with CHD, and high-density lipoprotein cholesterol (HDLC) levels are negatively associated with CHD. Efforts to identify and treat people at increased risk based on cholesterol and lipoprotein levels have led to more lipid testing and the need for very reliable test results. Thus, quality laboratory services are an essential component of healthcare delivery and play a vital role in any strategy to reduce morbidity and mortality from CHD. In laboratories with limited resources, establishing laboratory capability to measure CHD risk markers may be a considerable challenge. Laboratories face problems in selecting proper techniques, difficulties in equipment availability and maintenance, and shortage of supplies, staffing, and supervision. The Centers for Disease Control and Prevention (CDC) has been providing technical assistance for more than 30 years to laboratories that measure lipids and lipoproteins and is willing to provide technical assistance as needed for other laboratories to develop this capability. CDC can provide technical assistance to establish lipid and lipoprotein testing capability to support a CHD public health program in areas with limited laboratory resources. This assistance includes: selecting a suitable testing instrument; providing training for laboratory technicians; establishing a simple quality control plan; and instructing staff on how to prepare frozen serum control materials suitable for assessing accuracy of lipid and lipoprotein testing.

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-1-lipoprotein immuno-logical test system....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... the alpha-1-lipoprotein (high-density lipoprotein) in serum and plasma. Measurement of alpha-1...

The determination of density and molecular weight distributions of lipoproteins by sedimentation equilibrium.

PubMed

Jeffrey, P D; Nichol, L W; Smith, G D

1975-01-25

A method is presented by which an experimental record of total concentration as a function of radial distance, obtained in a sedimentation equilibrium experiment conducted with a noninteracting mixture in the absence of a density gradient, may be analyzed to obtain the unimodal distributions of molecular weight and of partial molar volume when these vary concomitantly and continuously. Particular attention is given to the caracterization of classes of lipoproteins exhibiting Gaussian distributions of these quantities, although the analysis is applicable to other types of unimodal distribution. Equations are also formulated permitting the definition of the corresponding distributions of partial specific volume and of density. The analysis procedure is based on a method (employing Laplace transforms) developed previously, but differs from it in that it avoids the necessity of differentiating experimental results, which introduces error. The method offers certain advantages over other procedures used to characterize and compare lipoprotein samples (exhibiting unimodal distributions) with regard to the duration of the experiment, economy of the sample, and, particularly, the ability to define in principle all of the relevant distributions from one sedimentation equilibrium experiment and an external measurement of the weight average partial specific volume. These points and the steps in the analysis procedure are illustrated with experimental results obtained in the sedimentation equilibrium of a sample of human serum low density lipoprotein. The experimental parameters (such as solution density, column height, and angular velocity) used in the conduction of these experiments were selected on the basis of computer-simulated examples, which are also presented. These provide a guide for other workers interested in characterizing lipoproteins of this class.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease.

PubMed

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(-)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(-), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

PubMed Central

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(–)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(–), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk. PMID:26357481

Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

PubMed

Oda, Hitomi; Mori, Akihiro; Hirowatari, Yuji; Takoura, Toshie; Manita, Daisuke; Takahashi, Tomoya; Shono, Saori; Onozawa, Eri; Mizutani, Hisashi; Miki, Yohei; Itabashi, Yukiko; Sako, Toshinori

2017-10-01

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who take hydroxymethylglutaryl-CoA reductase inhibitors, vitamin B6, and folic acid.

PubMed

Shojaei, Mir Hatef; Djalali, Mamhmoud; Siassi, Fereydoun; Khatami, Mohammad Reza; Boroumand, Mohammad Ali; Eshragian, Mohammad Reza

2009-07-01

High serum levels of lipoprotein(a) and homocysteine are risk factors of cardiovascular disease which are prevalent in patients on hemodialysis. Controversy exists about the effects of hydroxymethylglutaryl-CoA reductase inhibitors on serum lipoprotein(a) levels in patients on hemodialysis. Also, deficiency of some water soluble vitamins and administration of statins may raise serum levels of homocysteine in these patients. This study was designed to investigate serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who were taking a statin, vitamin B6, and folic acid. We investigated on 152 patients with maintenance hemodialysis who were taking atorvastatin or lovastatin, vitamin B6, and folic acid for at least 6 months. Their serum levels were obtained to measure lipoprotein(a) and homocysteine levels, as well as triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The mean serum values of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and triglyceride were significantly less than the maximum reference values (P < .001). The mean serum level of lipoprotein(a) was also less than the reference value (P = .009), but homocysteine level was 33% higher on average than the reference value (P < .001). Our study demonstrated that in our patients on hemodialysis, the mean serum level of homocysteine was about 30% higher than the reference value although they were receiving vitamin B6 and folic acid. Hence, they were still exposed to the risk of cardiovascular disease.

Apolipoprotein-containing lipoprotein subclasses and subclinical atherosclerosis in systemic lupus erythematosus.

PubMed

Kiani, Adnan N; Fang, Hong; Akhter, Ehtisham; Quiroga, Carmen; Simpson, Nancy; Alaupovic, Petar; Magder, Laurence S; Petri, Michelle

2015-03-01

Traditional classification of hyperlipidemia using high-density lipoprotein, low-density lipoprotein (LDL), and very low-density lipoprotein does not provide information on lipoprotein function. Apolipoproteins (Apos), which are protein components of plasma lipoproteins (including A, B, C, D, E) with their different composition, metabolic, and atherogenic properties, provide insight on lipoprotein functioning. In particular, the Apo B/A-I ratio is associated with atherogenic LDL and development of cardiovascular disease. We explored the baseline association between these nontraditional risk factors with subclinical measures of atherosclerosis (coronary artery calcification [CAC] and carotid intima-media thickness [IMT]) in systemic lupus erythematosus (SLE). A total of 58 SLE patients (97% women, 58% white, 40% African American, and 2% other, mean ± SD age 44 ± 11 years) had measurement of Apo and lipoproteins by immunoturbidimetric procedures, electroimmunoassays, and immunoprecipitation. CAC was measured by helical computed tomography and carotid IMT by carotid duplex. This study was based on the baseline assessment of subclinical atherosclerosis in the Lupus Atherosclerosis Prevention Study. The measurement of the lipoproteins was made on sera collected at the same time. There was no association between cardioprotective Apos (Apo A-I, LpA-I, LpA-I:A-II) and CAC (P < 0.15, P < 0.41, and P < 0.39, respectively) or carotid IMT (P < 0.97, P < 0.53, and P < 0.76, respectively). CAC and carotid IMT did not associate with atherogenic Apos either, including LpB:E+LpB:C:E, Apo B, LpB, LpB:C, Apo C-III, Apo C-III-HS, Apo C-III-HP, Apo C-III-R, LpA-II:B:C:D:E, and Apo B/Apo A-I. Measures of disease activity, including physician's global assessment and Systemic Lupus Erythematosus Disease Activity Index, were not associated with CAC or carotid IMT. Neither cardioprotective nor atherogenic lipoproteins were associated with measures of subclinical atherosclerosis in this series of SLE patients. Further studies with a larger sample size are warranted to confirm our findings.

Operation Everest II. Plasma Lipid and Hormonal Responses

DTIC Science & Technology

1988-01-01

cholesterol [TC] and high density lipoprotein cholesterol [ HDL -C] concentrations are shown in Fig 2. Pre-ascent...of altitude on fasting total cholesterol and high density lipoprotein ( HDL ) cholesterol concentrations. ** = p<O.Ol from 760 Torr Figure 3: The effect...157.7*9.7 mg/dl, decreased by 25% to .6 118.3*13.5 mg/dl following the 40-day exposure (p<O.Ol). High density lipoprotein [ HDL -C] levels

Ion mobility analysis of lipoproteins

DOEpatents

Benner, W Henry [Danville, CA; Krauss, Ronald M [Berkeley, CA; Blanche, Patricia J [Berkeley, CA

2007-08-21

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

Aerosol preparation of intact lipoproteins

DOEpatents

Benner, W Henry [Danville, CA; Krauss, Ronald M [Berkeley, CA; Blanche, Patricia J [Berkeley, CA

2012-01-17

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism.

PubMed

Watts, Gerald F; Chan, Dick C; Dent, Ricardo; Somaratne, Ransi; Wasserman, Scott M; Scott, Rob; Burrows, Sally; R Barrett, P Hugh

2017-01-24

Monoclonal antibodies against proprotein convertase subtilisin kexin type 9 (PCSK9), such as evolocumab, lower plasma low-density lipoprotein (LDL)-cholesterol concentrations. Evolocumab is under investigation for its effects on cardiovascular outcomes in statin-treated, high-risk patients. The mechanism of action of PCSK9 monoclonal antibodies on lipoprotein metabolism remains to be fully evaluated. Stable isotope tracer kinetics can effectively elucidate the mode of action of new lipid-regulating pharmacotherapies. We conducted a 2-by-2 factorial trial of the effects of atorvastatin (80 mg daily) and subcutaneous evolocumab (420 mg every 2 weeks) for 8 weeks on the plasma kinetics of very-low-density lipoprotein (VLDL)-apolipoprotein B-100 (apoB), intermediate-density lipoprotein-apoB, and LDL-apoB in 81 healthy, normolipidemic, nonobese men. The kinetics of apoB in these lipoproteins was studied using a stable isotope infusion of D3-leucine, gas chromatography/mass spectrometry, and multicompartmental modeling. Atorvastatin and evolocumab independently accelerated the fractional catabolism of VLDL-apoB (P<0.001 and P.032, respectively), intermediate-density lipoprotein-apoB (P=0.021 and P=.002, respectively), and LDL-apoB (P<0.001, both interventions). Evolocumab but not atorvastatin decreased the production rate of intermediate-density lipoprotein-apoB (P=0.043) and LDL-apoB (P<0.001), which contributed to the reduction in the plasma pool sizes of these lipoprotein particles. The reduction in LDL-apoB and LDL-cholesterol concentrations was significantly greater with combination versus either monotherapy (P<0.001). Whereas evolocumab but not atorvastatin lowered the concentration of free PCSK9, atorvastatin lowered the lathosterol/campesterol ratio (a measure of cholesterol synthesis/absorption) and apoC-III concentration. Both interventions decreased plasma apoE, but neither significantly altered lipoprotein lipase and cholesteryl ester protein mass or measures of insulin resistance. In healthy, normolipidemic subjects, evolocumab decreased the concentration of atherogenic lipoproteins, particularly LDL, by accelerating their catabolism. Reductions in intermediate-density lipoprotein and LDL production also contributed to the decrease in LDL particle concentration with evolocumab by a mechanism distinct from that of atorvastatin. These kinetic findings provide a metabolic basis for understanding the potential benefits of PCSK9 monoclonal antibodies incremental to statins in on-going clinical end point trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02189837. © 2016 American Heart Association, Inc.

Supplementation with Watermelon Extract Reduces Total Cholesterol and LDL Cholesterol in Adults with Dyslipidemia under the Influence of the MTHFR C677T Polymorphism.

PubMed

Massa, Nayara M L; Silva, Alexandre S; de Oliveira, Caio V C; Costa, Maria J C; Persuhn, Darlene C; Barbosa, Carlos V S; Gonçalves, Maria da C R

2016-08-01

Dyslipidemia and genetic polymorphisms are associated with increased risk for developing cardiovascular diseases, and watermelon appears to have the potential to improve hyperlipidemia due to the presence of nutrients such as arginine and citrulline. To test the hypolipidemic effect of watermelon extract (Citrullus lanatus) and the influence of the methylenetetrahydrofolate reductase genotype (MTHFR C677T) on supplementation response. This is an experimental clinical phase II randomized and double-blind study. Forty-three subjects with dyslipidemia were randomly divided into 2 groups: experimental (n = 22) and control (n = 21) groups. The subjects were supplemented daily for 42 days with 6 g of watermelon extract or a mixture of carbohydrates (sucrose/glucose/fructose). The use of watermelon extract reduced plasma total cholesterol (p < 0.05) and low-density lipoprotein (p < 0.01) without modifying triglycerides, high-density lipoprotein, and very low-density lipoprotein values. Only carriers of the T allele (MTHFR C677T) showed decreasing concentrations of low-density lipoprotein (p < 0.01). No changes in anthropometric parameters analyzed were observed. This is the first study to demonstrate the beneficial effect of the consumption of watermelon extract in reducing plasma levels of lipids in humans. The MTHFR C677T polymorphism did not affect the plasma lipid concentration but made individuals more responsive to treatment with watermelon. The consumption of this functional food represents an alternative therapy in the combined treatment of patients with dyslipidemia, promoting health and minimizing the development of risk factors for cardiovascular diseases.

Analysis of Pediatric Waist to Hip Ratio Relationship to Metabolic Syndrome Markers.

PubMed

Moore, Lindy M; Fals, Angela M; Jennelle, Pamela J; Green, Jeanette F; Pepe, Julie; Richard, Tere

2015-01-01

Waist to hip ratio (WHR) is a valid assessment tool to determine risk for the development or presence of metabolic syndrome, diabetes, and cardiovascular disease in adults. Evidence-based research on its validity with children and adolescents is limited. A retrospective analysis was conducted to determine if WHR in overweight and obese pediatric patients is associated with metabolic syndrome laboratory markers. Retrospective chart reviews were performed for 754 patients ages 6 to 17 years who were enrolled in a weight management program. Data collected included WHR, laboratory markers for metabolic disorder, body mass index, demographics, presence of acanthosis nigricans, and Tanner stage. WHR and high-density lipoprotein were negatively correlated, r (N = 597) = -0.20, p < .001. WHR and triglycerides were positively correlated, r (N = 597) = 0.19, p < .001, as were WHR and low-density lipoprotein, r (N = 596) = 0.09, p = .03, and WHR and insulin, r (N = 414) = 0.16, p = .001. In a subject sample with very restricted range, a one-way analysis of variance found a significant effect of WHR on body mass index percentile, F (1, 754) = 22.43, p < .001, η(2) = 0.03. Increased WHR correlated in children and adolescents with known indicators that could be suggestive of increased risk for metabolic syndrome, specifically low high-density lipoprotein, high low-density lipoprotein, triglycerides, and insulin. These results suggest that evaluation of WHR may be a useful tool to indicate risk for developing metabolic syndrome and diabetes in children and adolescents. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

New Drugs for Treating Dyslipidemia: Beyond Statins

PubMed Central

Ahn, Chang Ho

2015-01-01

Statins have been shown to be very effective and safe in numerous randomized clinical trials, and became the implacable first-line treatment against atherogenic dyslipidemia. However, even with optimal statin treatment, 60% to 80% of residual cardiovascular risk still exists. The patients with familial hypercholesterolemia which results in extremely high level of low density lipoprotein cholesterol (LDL-C) level and the patients who are intolerant or unresponsive to statins are the other hurdles of statin treatment. Recently, new classes of lipid-lowering drugs have been developed and some of them are available for the clinical practice. The pro-protein convertase subtilisin/kexintype 9 (PCSK9) inhibitor increases the expression of low density lipoprotein (LDL) receptor in hepatocytes by enhancing LDL receptor recycling. The microsomal triglyceride transport protein (MTP) inhibitor and antisense oligonucleotide against apolipoprotein B (ApoB) reduce the ApoB containing lipoprotein by blocking the hepatic very low density lipoprotein synthesis pathway. The apolipoprotein A1 (ApoA1) mimetics pursuing the beneficial effect of high density lipoprotein cholesterol and can reverse the course of atherosclerosis. ApoA1 mimetics had many controversial clinical data and need more validation in humans. The PCSK9 inhibitor recently showed promising results of significant LDL-C lowering in familial hypercholesterolemia (FH) patients from the long-term phase III trials. The MTP inhibitor and antisesnse oligonucleotide against ApoB were approved for the treatment of homozygous FH but still needs more consolidated evidences about hepatic safety such as hepatosteatosis. We would discuss the benefits and concerns of these new lipid-lowering drugs anticipating additional benefits beyond statin treatment. PMID:25922802

Serum lipoprotein concentrations in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaughan, W.J.; Lindgren, F.T.; Whalen, J.B.

1978-02-17

Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules.

Use of lipoprotein particle measures for assessing coronary heart disease risk post-American Heart Association/American College of Cardiology guidelines: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Steffen, Brian T; Guan, Weihua; Remaley, Alan T; Paramsothy, Pathmaja; Heckbert, Susan R; McClelland, Robyn L; Greenland, Philip; Michos, Erin D; Tsai, Michael Y

2015-02-01

The American College of Cardiology and American Heart Association have issued guidelines indicating that the contribution of apolipoprotein B-100 (ApoB) to cardiovascular risk assessment remains uncertain. The present analysis evaluates whether lipoprotein particle measures convey risk of coronary heart disease (CHD) in 4679 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Cox regression analysis was performed to determine associations between lipids or lipoproteins and primary CHD events. After adjustment for nonlipid variables, lipoprotein particle levels in fourth quartiles were found to convey significantly greater risk of incident CHD when compared to first quartile levels (hazard ratio [HR]; 95% confidence interval [CI]): ApoB (HR, 1.84; 95% CI, 1.25-2.69), ApoB/ApoA-I (HR, 1.91; 95% CI, 1.32-2.76), total low-density lipoprotein-particles (LDL-P; HR, 1.77; 95% CI, 1.21-2.58), and the LDL-P/HDL-P (high-density lipoprotein-P) ratio (HR, 2.28; 95% CI, 1.54-3.37). Associations between lipoprotein particle measures and CHD were attenuated after adjustment for standard lipid panel variables. Using the American Heart Association/American College of Cardiology risk calculator as a baseline model for CHD risk assessment, significant net reclassification improvement scores were found for ApoB/ApoA-I (0.18; P=0.007) and LDL-P/high-density lipoprotein-P (0.15; P<0.001). C-statistics revealed no significant increase in CHD event discrimination for any lipoprotein measure. Lipoprotein particle measures ApoB/ApoA-I and LDL-P/high-density lipoprotein-P marginally improved net reclassification improvement scores, but null findings for corresponding c-statistic are not supportive of lipoprotein testing. The attenuated associations of lipoprotein particle measures with CHD after the adjustment for lipids indicate that their measurement does not detect risk that is unaccounted for by the standard lipid panel. However, the possibility that lipoprotein measures may identify CHD risk in a subpopulation of individuals with normal cholesterol, but elevated lipoprotein particle numbers cannot be ruled out. © 2014 American Heart Association, Inc.

Lipid paradox in acute myocardial infarction-the association with 30-day in-hospital mortality.

PubMed

Cheng, Kai-Hung; Chu, Chih-Sheng; Lin, Tsung-Hsien; Lee, Kun-Tai; Sheu, Sheng-Hsiung; Lai, Wen-Ter

2015-06-01

Elevated low-density lipoprotein cholesterol and triglycerides are major risk factors for coronary artery disease. However, fatty acids from triglycerides are a major energy source, low-density lipoprotein cholesterol is critical for cell membrane synthesis, and both are critical for cell survival. This study was designed to clarify the relationship between lipid profile, morbidity as assessed by Killip classification, and 30-day mortality in patients with acute myocardial infarction. A noninterventional observational study. Coronary care unit in a university hospital. Seven hundred twenty-four patients with acute myocardial infarction in the coronary care program of the Bureau of Health Promotion were analyzed. None. Low-density lipoprotein cholesterol and triglyceride levels were significantly lower in high-Killip (III+IV) patients compared with low-Killip (I+II) patients and in those who died compared with those who survived beyond 30 days (both p<0.001). After adjustment for risk factors, low-density lipoprotein cholesterol less than 62.5 mg/dL and triglycerides less than 110 mg/dL were identified as optimal threshold values for predicting 30-day mortality and were associated with hazard ratios of 1.65 (95% CI, 1.18-2.30) and 5.05 (95% CI, 1.75-14.54), and the actual mortality rates were 23% in low low-density lipoprotein, 6% in high low-density lipoprotein, 14% in low triglycerides, and 3% in high triglycerides groups, respectively. To test the synergistic effect, high-Killip patients with triglycerides less than 62.5 mg/dL and low-density lipoprotein cholesterol less than 110 mg/dL had a 10.9-fold higher adjusted risk of mortality than low-Killip patients with triglycerides greater than or equal to 62.5 mg/dL and low-density lipoprotein cholesterol greater than or equal to 110 mg/dL (p<0.001). The lipid paradox also improved acute myocardial infarction short-term outcomes prediction on original Killip and thrombolytic in myocardial infarction scores. Low low-density lipoprotein cholesterol, low triglycerides, and high Killip severity were associated with significantly higher 30-day in-hospital mortality in patients presenting with acute myocardial infarction. The initial lipid profile of patients with acute myocardial infarction may therefore hold prognostic value.

Pitavastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol'). Pitavastatin is in a class of ...

Enhancement of antioxidative activity and cardiovascular protection in hamsters by camellia oil and soybean-camellia blended oil.

PubMed

Chou, Ting-Yi; Lu, Yi-Fa; Inbaraj, Baskaran Stephen; Chen, Bing-Huei

2018-02-07

The aim of this study was to examine the effects of several vegetable oils and blended oil composed of soybean and camellia oils on blood lipid reduction and antioxidative activity. Forty male hamsters were fed an AIN-93 G diet for 1 wk, followed by dividing into five groups: control group-1 was fed a low-fat diet containing 5% oil for 6 wk, and the other four groups were fed high-fat diets with group-2 containing 14% palm oil, group-3 containing 14% camellia oil, group-4 containing 14% soybean oil, and group-5 containing 14% blended oil (8.4% soybean oil and 5.6% camellia oil) along with 0.2% cholesterol and 0.1% bile acid. High-fat diets raised serum triacylglycerol, total cholesterol, and aspartate aminotransferase in hamsters without affecting alanine aminotransferase. Compared with palm oil-containing diet, the other three high-fat diets reduced serum total cholesterol, low-density lipoprotein cholesterol, and the ratio of low-density lipoprotein to high-density lipoprotein cholesterol with an opposite trend for liver total cholesterol. However, compared with the control group, the serum high-density lipoprotein cholesterol level was raised for all four high-fat diets. The higher the degree of oil unsaturation, the higher the serum thiobarbituric acid reactive substances and the lower the liver triacylglycerol level and activities of fatty acid synthase, glucose 6-phosphate dehydrogenase, and malic enzymes. Both soybean and blended oils lowered the antioxidative activity of liver. Camellia and blended oils were more efficient than soybean oil in elevating serum high-density lipoprotein cholesterol and decreasing the ratio of low-density lipoprotein to high-density lipoprotein cholesterol in hamsters. Copyright © 2018 Elsevier Inc. All rights reserved.

Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C.

PubMed

Chapman, M John; Assmann, Gerd; Fruchart, Jean-Charles; Shepherd, James; Sirtori, Cesare

2004-08-01

Reduction of low-density lipoprotein cholesterol (LDL-C) is presently the primary focus of lipid-lowering therapy for prevention and treatment of coronary heart disease (CHD). However, the high level of residual risk among statin-treated patients in recent coronary prevention studies indicates the need for modification of other major components of the atherogenic lipid profile. There is overwhelming evidence that a low plasma level of high-density lipoprotein cholesterol (HDL-C) is an important independent risk factor for CHD. Moreover, a substantial proportion of patients with or at risk of developing premature CHD typically exhibit distinct lipid abnormalities, including low HDL-C levels. Thus, therapeutic intervention aimed at raising HDL-C, within the context of reducing global cardiovascular risk, would benefit such patients, a viewpoint increasingly adopted by international treatment guidelines. Therapeutic options for patients with low HDL-C include treatment with statins, fibrates and nicotinic acid, either as monotherapy or in combination. Of these options, nicotinic acid is not only the most potent agent for raising HDL-C but is also effective in reducing key atherogenic lipid components including triglyceride-rich lipoproteins (mainly very low-density lipoproteins [VLDL] and VLDL remnants), LDL-C, and lipoprotein(a). The principal features of the atherogenic lipid profile in type 2 diabetes and the metabolic syndrome make them logical targets for nicotinic acid therapy, either alone or in combination with a statin. The lack of comprehensive European data on the prevalence of low HDL-C levels highlights a critical need for education on the importance of raising HDL-C in CHD prevention and treatment. The development of a reliable and accurate assay for HDL-C, as well as clarification of criteria for low and optimal levels of HDL-C in both men and women, constitute critical factors in the reliable identification and treatment of patients at elevated risk of CHD due to low HDL-C. Based on the available evidence, the European Consensus Panel recommends that the minimum target for HDL-C should be 40 mg/dL (1.03 mmol/L) in patients with CHD or with a high level of risk for CHD, including patients at high global risk with type 2 diabetes or the metabolic syndrome.

Effect of Exercise Training on Cardiac Biomarkers in At-Risk Populations: A Systematic Review.

PubMed

Glenney, Susan Sullivan; Brockemer, Derrick Paul; Ng, Andy C; Smolewski, Michael A; Smolgovskiy, Vladimir M; Lepley, Adam S

2017-12-01

Studies have demonstrated beneficial effects of exercise on cardiovascular disease biomarkers for healthy individuals; however, a comprehensive review regarding the effect of exercise on cardiovascular disease biomarkers in at-risk populations is lacking. A literature search was performed to identify studies meeting the following criteria: randomized controlled study, participants with pathology/activity limitations, biomarker outcome (total cholesterol, high-density lipoprotein, low-density lipoprotein, C-reactive protein, insulin, triglycerides, or glucose), and exercise intervention. Means and standard deviations from each biomarker were used to calculate standardized Cohen's d effect sizes with 95% confidence intervals. In total, 37 articles were included. The majority (44/57; 77%) of data points demonstrated moderate to strong effects for the reduction in total cholesterol, triglycerides, and low-density lipoprotein, and elevation in high-density lipoprotein following exercise. The majority of data points demonstrated strong effects for reductions in blood glucose (24/30; 80%) and insulin (23/24; 96%) levels following exercise intervention. Evidence is heterogeneous regarding the influence of exercise on cardiovascular disease biomarkers in at-risk patients, which does not allow a definitive conclusion. Favorable effects include reductions in triglycerides, total cholesterol, low-density lipoprotein, glucose, and insulin, and elevation in high-density lipoprotein following exercise intervention. The strongest evidence indicates that exercise is favorable for the reduction in glucose and cholesterol levels among obese patients, and reduction of insulin regardless of population.

Rosuvastatin enhances the catabolism of LDL apoB-100 in subjects with combined hyperlipidemia in a dose dependent manner

USDA-ARS?s Scientific Manuscript database

Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypo...

Fluvastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Fluvastatin may also ...

Simvastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also ...

Pravastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Pravastatin is in ...

Determining the risk of cardiovascular disease using ion mobility of lipoproteins

DOEpatents

Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

2010-05-11

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

[The influence of nettle and burdock extracts in combination with different diets on dyslipidemia in diabetes mellitus model].

PubMed

Vengerovsky, A I; Yakimova, T V; Nasanova, O N

2015-01-01

The influence of low-fat diet, nettle (Urtica dioica) leafs and burdock (Arctium lappa) roots extracts on lipid metabolism and glycosylation reactions has been investigated in experimental diabetes mellitus. These extracts were applied in diets with both high and low fat content. The experiments were performed on 90 noninbred male albino rats (200–220 g) that were divided into 9 experimental groups. Diabetes mellitus was modeled with twice-repeated intraperitoneal streptozotocin (30 mg/kg) injections. The animals received food with increased fat content (proteins – 8%, fats – 30%, carbohydrates – 62% of total daily caloric content) during 4 weeks before streptozotocine injections and 8 weeks after its discontinuation. Simultaneously the rats were daily administered nettle leafs (100 mg/kg), burdock roots (25 mg/kg) extracts or metformin (100 mg/kg) into the stomach during 10 days. During the period of agents introduction half the animals continued to receive food with high fat content, the other half received low fat diet (proteins – 20%, fats – 8%, carbohydrates – 72% of the total daily caloric content). The forth (control) group received low fat food only without extracts or metformin administration. The levels of blood glucose, glycosylated hemoglobin, malonic dialdehyde, lipid and lipoprotein fractions content were measured. It has been shown that after streptozotocine injections and 30% fat diet consumption the blood glucose level increased by 5.3 fold compared to that of the intact animals, the content of atherogenic lipid fractions increased by 2–8.3 fold and the protein glycosylation reactions were intensified by 1.9–2.5 fold. In animals fed with 8% fat diet the blood glucose and malonic dialdehyde content decreased by 1.8–2.3 fold. In this experiment the levels of triglycerides, total cholesterol, cholesterol of nonhigh-density lipoproteins, low-density and very low-density lipoproteins, as well as the cholesterol and protein content of high-density lipoproteins normalized. The low fat food did not cause glycosylation reactions regression. With the administration of nettle, burdock extracts or metformin to animals that continued to receive high fat food the blood glucose, triglycerides, total cholesterol, cholesterol of nonhigh-density lipoproteins, low-density and very low-density lipoproteins levels decreased by l.6–7.l fold as compared to the parameters in streptozotocine diabetes mellitus. Cholesterol and protein content of high-density lipoproteins increased by l.4–3.7 fold. The herbal extracts also prevented malonic dialdehyde formation, high-density lipoproteins and hemoglobin glycosylation. The nettle and burdock extracts more effectively decreased hyperglycemia, hypertriglyceridemia and lipoperoxidation in animals fed with low fat food. Metformin in the experiment with low fat intake decreased the glucose, low-density and very low-density lipoproteins content to a maximal degree and prevented high-density lipoproteins glycosylation.

High density lipoprotein cholesterol is associated with serum cortisol in older people.

PubMed

Varma, V K; Rushing, J T; Ettinger, W H

1995-12-01

To determine the associations between serum cortisol and HDL cholesterol, other lipoprotein lipids and cardiovascular risk factors, carotid atherosclerosis, and clinical heart disease in older people. A cross-sectional, observational, ancillary study of the Cardiovascular Health Study (CHS). A total of 245 community-dwelling people, 65 to 89 years old, were recruited consecutively for a 2-month period from the CHS cohort in Forsyth County, North Carolina. Cortisol was measured by radioimmunoassay in serum collected between 7:00 and 10:00 AM after an overnight fast. Cortisol levels were correlated with lipoprotein lipids, insulin, glucose, body mass index, waist-hip ratio, prevalent coronary heart disease, hypertension, diabetes, and carotid atherosclerosis by B-mode ultrasound. Serum cortisol was correlated negatively (r = -.24) with body mass index and waist-hip ratio (r = -.16) but was not related significantly to fasting insulin or glucose. Cortisol was not associated significantly with triglyceride and low density lipoprotein cholesterol but showed a positive correlation (r = .21) with high density lipoprotein cholesterol. The relationship between cortisol and high density lipoprotein cholesterol persisted after adjustment for gender, body mass index, waist-hip ratio, cigarette and alcohol use, triglyceride level, and diabetes. There was a trend toward a negative correlation between cortisol and measures of carotid atherosclerosis, but no significant relationship was indicated between cortisol and prevalent coronary heart disease, hypertension, or diabetes. Endogenous glucocorticoid levels correlated with HDL cholesterol levels and may play a role in the physiologic regulation of high density lipoprotein levels in older people.

Characterization of blood lipoproteins and validation of cholesterol and triacylglycerol assays for free-ranging polar bears (Ursus maritimus).

PubMed

Whiteman, John P; Frank, Nicholas; Greller, Katie A; Harlow, Henry J; Ben-David, Merav

2013-05-01

Blood triacylglycerol (TG) and lipoproteins are important variables for evaluating nutritional status of wildlife, but measurements are often expensive and difficult. Performance of a small, portable blood analyzer intended for human medical diagnostics was evaluated in measuring these variables in plasma and serum from free-ranging polar bears (Ursus maritimus), which are experiencing nutritional stress related to sea ice loss. The analyzer accurately tracked changes in concentration of total cholesterol (Ctotal), cholesterol associated with high-density lipoprotein (CHDL), and TG during a validation protocol of diluting samples and spiking them with exogenous cholesterol and glycerol. Values of Ctotal and TG agreed well with values obtained by other methods (ultracentrifugation followed by colorimetric assays); agreement was variable for values of cholesterol associated with specific lipoproteins. Similar to a study of captive polar bears, ultracentrifugation methods revealed greater TG in very low-density lipoproteins than in low-density lipoprotein, which is unusual and merits additional study.

Plasma lipids, lipoprotein composition and profile during induction and treatment of hepatic lipidosis in cats and the metabolic effect of one daily meal in healthy cats.

PubMed

Blanchard, G; Paragon, B M; Sérougne, C; Férézou, J; Milliat, F; Lutton, C

2004-04-01

Anorexia in obese cats may result in feline hepatic lipidosis (FHL). This study was designed to determine plasma lipids and lipoprotein profiles in queens at different stages during experimental induction of FHL (lean, obese, FHL), and after 10 weeks of treatment. Results were compared with those obtained from lean queens of same age fed the same diet but at a maintenance level, once a day. Hepatic lipidosis led to an increase in plasma triacylglycerol (TG), very low density lipoprotein (VLDL) and low density lipoprotein (LDL), and an enrichment of LDL with TG and of high density lipoprotein (HDL) with cholesterol, suggesting that VLDL secretion is enhanced, VLDL and LDL catabolism is lowered, and lipoprotein exchanges are impaired in FHL. This study also showed that cholesterolaemia is increased in cats fed at a dietary rhythm of one meal per day compared to ad libitum feeding.

HDL: The "Good" Cholesterol

MedlinePlus

... and LDL (bad) cholesterol: HDL stands for high-density lipoproteins. It is called the "good" cholesterol because ... cholesterol from your body. LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because ...

LDL: The "Bad" Cholesterol

MedlinePlus

... and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because ... cholesterol in your arteries. HDL stands for high-density lipoproteins. It is called the "good" cholesterol because ...

The Impact of Cardiorespiratory Fitness on Age-Related Lipids and Lipoproteins

PubMed Central

Park, Yong-Moon Mark; Sui, Xuemei; Liu, Junxiu; Zhou, Haiming; Kokkinos, Peter F.; Lavie, Carl J.; Hardin, James W.; Blair, Steven N.

2015-01-01

Background Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. Objectives This study sought to assess the longitudinal, aging trajectory of lipids and lipoproteins for the life course in adults, and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Methods Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 (mean 3.5) health examinations between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Results Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until the mid-40s to early 50s, with subsequent declines (all p < 0.0001). Compared to men with higher CRF, those with lower CRF developed abnormal values earlier in life: TC (≥200 mg/dl), LDL-C (≥130 mg/dl), non-HDL-C (≥160 mg/dl), and TG/HDL-C ratio (≥3.0). Notably, abnormal values for TC and LDL-C in men with low CRF were observed around 15 years earlier than in those with high CRF. After adjusting for time-varying covariates, a significant interaction was found between age and CRF in each trajectory, indicating that CRF was more strongly associated with the aging trajectories of lipids and lipoproteins in young to middle-aged men than in older men. Conclusions Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men, and suggests that promoting increased CRF levels may help delay the development of dyslipidemia. PMID:25975472

Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice.

PubMed

Lambert, G; Sakai, N; Vaisman, B L; Neufeld, E B; Marteyn, B; Chan, C C; Paigen, B; Lupia, E; Thomas, A; Striker, L J; Blanchette-Mackie, J; Csako, G; Brady, J N; Costello, R; Striker, G E; Remaley, A T; Brewer, H B; Santamarina-Fojo, S

2001-05-04

To evaluate the biochemical and molecular mechanisms leading to glomerulosclerosis and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density lipoprotein receptor (LDLr) KO, and cholesteryl ester transfer protein transgenic mice. LCAT-KO mice had normochromic normocytic anemia with increased reticulocyte and target cell counts as well as decreased red blood cell osmotic fragility. A subset of LCAT-KO mice accumulated lipoprotein X and developed proteinuria and glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli. LCAT deficiency reduced the plasma high density lipoprotein (HDL) cholesterol (-70 to -94%) and non-HDL cholesterol (-48 to -85%) levels in control, apoE-KO, LDLr-KO, and cholesteryl ester transfer protein-Tg mice. Transcriptome and Western blot analysis demonstrated up-regulation of hepatic LDLr and apoE expression in LCAT-KO mice. Despite decreased HDL, aortic atherosclerosis was significantly reduced (-35% to -99%) in all mouse models with LCAT deficiency. Our studies indicate (i) that the plasma levels of apoB containing lipoproteins rather than HDL may determine the atherogenic risk of patients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role for lipoproteins X in the development of glomerulosclerosis in LCAT deficiency. The availability of LCAT-KO mice characterized by lipid, hematologic, and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulosclerosis in LCAT-deficient states.

TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study).

PubMed

Meier, C; Staub, J J; Roth, C B; Guglielmetti, M; Kunz, M; Miserez, A R; Drewe, J; Huber, P; Herzog, R; Müller, B

2001-10-01

This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol.

Habitual Diet and Avocado Trial

ClinicalTrials.gov

2018-06-19

Intra-abdominal Fat; Metabolic Syndrome; High Cholesterol; Triglycerides High; Diet Habit; High Blood Sugar; Liver Fat; Dietary Modification; HDL Cholesterol, Low Serum; Cardiovascular Diseases; High Density Lipoprotein Deficiency; Low-density-lipoprotein-type; Cardiovascular Risk Factor; Diabetes

Method of assessing a lipid-related health risk based on ion mobility analysis of lipoproteins

DOEpatents

Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

2010-12-14

A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein

PubMed Central

Ito, Fumiaki; Ito, Tomoyuki; Suzuki, Chinatsu; Yahata, Tomoyo; Ikeda, Kazuyuki; Hamaoka, Kenji

2017-01-01

Reactive oxygen species (ROS) are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs) test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and high-density lipoprotein (HDL) were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg2+ precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg2+ precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity. PMID:28230785

The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein.

PubMed

Ito, Fumiaki; Ito, Tomoyuki; Suzuki, Chinatsu; Yahata, Tomoyo; Ikeda, Kazuyuki; Hamaoka, Kenji

2017-02-21

Reactive oxygen species (ROS) are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs) test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and high-density lipoprotein (HDL) were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg 2+ precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg 2+ precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity.

Very large database of lipids: rationale and design.

PubMed

Martin, Seth S; Blaha, Michael J; Toth, Peter P; Joshi, Parag H; McEvoy, John W; Ahmed, Haitham M; Elshazly, Mohamed B; Swiger, Kristopher J; Michos, Erin D; Kwiterovich, Peter O; Kulkarni, Krishnaji R; Chimera, Joseph; Cannon, Christopher P; Blumenthal, Roger S; Jones, Steven R

2013-11-01

Blood lipids have major cardiovascular and public health implications. Lipid-lowering drugs are prescribed based in part on categorization of patients into normal or abnormal lipid metabolism, yet relatively little emphasis has been placed on: (1) the accuracy of current lipid measures used in clinical practice, (2) the reliability of current categorizations of dyslipidemia states, and (3) the relationship of advanced lipid characterization to other cardiovascular disease biomarkers. To these ends, we developed the Very Large Database of Lipids (NCT01698489), an ongoing database protocol that harnesses deidentified data from the daily operations of a commercial lipid laboratory. The database includes individuals who were referred for clinical purposes for a Vertical Auto Profile (Atherotech Inc., Birmingham, AL), which directly measures cholesterol concentrations of low-density lipoprotein, very low-density lipoprotein, intermediate-density lipoprotein, high-density lipoprotein, their subclasses, and lipoprotein(a). Individual Very Large Database of Lipids studies, ranging from studies of measurement accuracy, to dyslipidemia categorization, to biomarker associations, to characterization of rare lipid disorders, are investigator-initiated and utilize peer-reviewed statistical analysis plans to address a priori hypotheses/aims. In the first database harvest (Very Large Database of Lipids 1.0) from 2009 to 2011, there were 1 340 614 adult and 10 294 pediatric patients; the adult sample had a median age of 59 years (interquartile range, 49-70 years) with even representation by sex. Lipid distributions closely matched those from the population-representative National Health and Nutrition Examination Survey. The second harvest of the database (Very Large Database of Lipids 2.0) is underway. Overall, the Very Large Database of Lipids database provides an opportunity for collaboration and new knowledge generation through careful examination of granular lipid data on a large scale. © 2013 Wiley Periodicals, Inc.

[The clinical biochemistry of hypo-lipedemic therapy and mechanisms of action of statins: the fatty acids, statins and diabetes mellitus].

PubMed

Titov, V N

2014-02-01

In liver statins inhibit synthesis of specific pool of cholesterol which is formed de novo by hepatocytes for monolayer of polar lipids at the surface of forming lipoproteins of very low density. The statins, decreasing content of non-esterified cholesterol in monolayer, activate hydrolysis of triglycerides in lipoproteins of very low density, formation of lipoproteins of low density and their absorption by cells through apoB-100 receptors. The statins, activating absorption of lipoproteins of low density, restore functional action of essential polyenoic fatty acids. The essential polyenoic fatty acids, fibrates and glitazones form in cells effective oleic version of metabolism when mitochondrions predominantly oxidize oleic fatty acid. The statins, non-activating oxidation in peroxisomes and inhibiting activity of stearil-KoA-desaturase, form in cells less effective palmitic variant of metabolism of fatty acids under oxidation of palmitic fatty acid in mitochondrions. The fatty acids are not enough under hydrolysis of exogenous triglycerides to synthesize optimal amount of ATP. The fatty acids accumulated in adipocytes are to be used. This is the cause of formation by statins the resistance to insulin. Functionally, lipoproteins of very low density and lipoproteins of low density are phylogenetically different. The former ones transfer fatty acids to cells in the form of triglycerides and the latter ones--in the form of ethers with alcohol cholesterol. The statins normalize absorption of essential polyenoic fatty acids by cells which manifest a physiological action named a pleotropic one.

Dietary Resistant Starch Supplementation Increases High-Density Lipoprotein Particle Number in Pigs Fed a Western Diet.

PubMed

Rideout, Todd C; Harding, Scott V; Raslawsky, Amy; Rempel, Curtis B

2017-05-04

Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week-old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (-20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total HDL particle number.

Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study.

PubMed

Lupton, Joshua R; Faridi, Kamil F; Martin, Seth S; Sharma, Sristi; Kulkarni, Krishnaji; Jones, Steven R; Michos, Erin D

2016-01-01

Cross-sectional studies have found an association between deficiencies in serum vitamin D, as measured by 25-hydroxyvitamin D (25[OH]D), and an atherogenic lipid profile. These studies have focused on a limited panel of lipid values including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Our study examines the relationship between serum 25(OH)D and an extended lipid panel (Vertical Auto Profile) while controlling for age, gender, glycemic status, and kidney function. We used the Very Large Database of Lipids, which includes US adults clinically referred for analysis of their lipid profile from 2009 to 2011. Our study focused on 20,360 subjects who had data for lipids, 25(OH)D, age, gender, hemoglobin A1c, insulin, creatinine, and blood urea nitrogen. Subjects were split into groups based on serum 25(OH)D: deficient (<20 ng/mL), intermediate (≥ 20-30 ng/mL), and optimal (≥ 30 ng/mL). The deficient group was compared to the optimal group using multivariable linear regression. In multivariable-adjusted linear regression, deficient serum 25(OH)D was associated with significantly lower serum HDL-C (-5.1%) and higher total cholesterol (+9.4%), non-HDL-C (+15.4%), directly measured LDL-C (+13.5%), intermediate-density lipoprotein cholesterol (+23.7%), very low-density lipoprotein cholesterol (+19.0%), remnant lipoprotein cholesterol (+18.4%), and TG (+26.4%) when compared with the optimal group. Deficient serum 25(OH)D is associated with significantly lower HDL-C and higher directly measured LDL-C, intermediate-density lipoprotein cholesterol, very low-density lipoproteins cholesterol, remnant lipoprotein cholesterol, and TG. Future trials examining vitamin D supplementation and cardiovascular disease risk should consider using changes in an extended lipid panel as an additional outcome measurement. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[Characteristics of fatty acid composition of phosphatidyl cholines and sphingomyelins of low-density lipoproteins in the plasma of native inhabitants of Chukotka].

PubMed

Gerasimova, E N; Levachev, M M; Perova, N V; Nikitin, Iu P; Ozerova, I N

1986-01-01

Contents of cholesterol, triglycerides, high density lipoproteins (HDL) cholesterol as well as phospholipid and fatty acid compositions of phosphatidyl cholines and sphingomyelins in low density lipoproteins (LDL) were studied in blood plasma of Chukot aborigenes--Eskimos as compared with Moscow inhabitants. In Eskimos content of HDL cholesterol was higher but concentration of cholesterol and triglycerides was lower in blood plasma. In LDL concentration of sphingomyelins was increased and fatty acid composition of phosphatidyl cholines and sphingomyelins was altered where amount of polyunsaturated fatty acids was elevated (20:5 + 22:5 + 22:6). The specific characteristics of the LDL phospholipids observed in Eskimos might be responsible for the higher liquid properties of the surface monolayer in the lipoproteins; this alteration might be important for the lipoprotein properties and transformation as well as for the properties of membrane-bound enzymes, for synthesis of thromboxane and prostacyclins.

Lipoprotein metabolism in Japanese centenarians: effects of apolipoprotein E polymorphism and nutritional status.

PubMed

Arai, Y; Hirose, N; Nakazawa, S; Yamamura, K; Shimizu, K; Takayama, M; Ebihara, Y; Osono, Y; Homma, S

2001-11-01

To assess the complex interaction of apolipoprotein (apo) E polymorphisms and environmental factors on lipoprotein profile in centenarians. Cross-sectional analysis. Tokyo metropolitan area. Seventy-five centenarians and 73 healthy older volunteers (mean age 63.1 +/- 10.0) living in the Tokyo metropolitan area. Plasma lipids and lipoproteins, cholesteryl ester transfer protein mass, apo E phenotype, body mass index, nutritional indices (serum albumin, prealbumin, transferrin), dietary intake, inflammation markers (C-reactive protein (CRP), interleukin-6 (IL-6)), activities of daily living, and cognitive function. In comparison with older people, the centenarians had low concentrations of total and low-density lipoprotein cholesterol (LDL-C) and a relative predominance of high-density lipoprotein 2 cholesterol. No environmental factor, except the number of apo E epsilon2 alleles, was a significant determinant of LDL-C and apo B, suggesting that the low apo B-containing lipoprotein in centenarians may be attributable to a genetic cause. Centenarians had elevated levels of lipoprotein (a) and decreased high-density lipoprotein cholesterol (HDL-C), which seem to be an unfavorable lipoprotein profile. Lower levels of HDL-C in the centenarians were associated with decreased serum albumin, elevated CRP and IL-6 levels, and cognitive impairment, suggesting that HDL-C could be a sensitive marker for frailty and comorbidity in the oldest old. Low levels of apo B-containing lipoproteins attributable to a genetic cause may be advantageous for longevity. Lipoprotein profiles in centenarians were consistently related to the subjects' nutritional status, inflammation markers, and apo E polymorphisms. The results provide evidence for the importance of maintaining nutritional status in the very old.

Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

USDA-ARS?s Scientific Manuscript database

Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

PubMed

Sabatti, Chiara; Service, Susan K; Hartikainen, Anna-Liisa; Pouta, Anneli; Ripatti, Samuli; Brodsky, Jae; Jones, Chris G; Zaitlen, Noah A; Varilo, Teppo; Kaakinen, Marika; Sovio, Ulla; Ruokonen, Aimo; Laitinen, Jaana; Jakkula, Eveliina; Coin, Lachlan; Hoggart, Clive; Collins, Andrew; Turunen, Hannu; Gabriel, Stacey; Elliot, Paul; McCarthy, Mark I; Daly, Mark J; Järvelin, Marjo-Riitta; Freimer, Nelson B; Peltonen, Leena

2009-01-01

Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

Small, qualitative changes in fatty acid intake decrease plasma low-density lipoprotein-cholesterol levels in mildly hypercholesterolemic outpatients on their usual high-fat diets.

PubMed

Lecerf, Jean-Michel; Luc, Gérald; Marécaux, Nadine; Bal, Sylvie; Bonte, Jean-Paul; Lacroix, Brigitte; Cayzeele, Amélie

2009-01-01

The diet is the first step in managing hypercholesterolemia. The objective of the present study is to assess whether moderate changes in dietary fatty acids improve plasma lipid parameters in mildly hypercholesterolemic outpatients. Using a randomized double-blind study, 121 outpatients within two groups received an isocaloric amount of unsaturated margarine or butter. Clinical and anthropometric measurements and a 3-day food record were made. Chi-square and Fisher's tests were used to compare qualitative variables and the general linear procedure was used to compare the groups. Additional analyses were performed after adjustment. There was a significant difference (P <0.03) in low-density lipoprotein-cholesterol levels between the groups. Total cholesterol, low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol and apolipoprotein B values decreased in the unsaturated group in comparison with the saturated group. Low-density lipoprotein-cholesterol changes were correlated with the variation in polyunsaturated fatty acid intake and with plasma phospholipid linoleic acid levels. A small change in saturated by polyunsaturated fatty acid intake may improve plasma lipid parameters in mildly hypercholesterolemic subjects.

Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish.

PubMed

Kim, Jae-Yong; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

2015-01-01

Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function.

Lipoprotein-cholesterol levels in infertile women with luteal phase deficiency.

PubMed

Hansen, K K; Knopp, R H; Soules, M R

1991-05-01

To determine if reductions in plasma progesterone (P) secretion seen in luteal phase deficiency (LPD) might be because of reduced availability of circulating low-density lipoprotein (LDL) or high-density lipoprotein (HDL), known substrates for corpus luteum P synthesis. We measured plasma lipoproteins in the luteal phase of the menstrual cycle in 39 infertile women. These women were divided into two groups on the basis of endometrial biopsies; the LPD group had biopsies that were greater than or equal to 3 days out-of-phase. All participants were recruited from the Reproductive Endocrinology and Infertility Clinic at the University of Washington, an institutional tertiary care center. Eighteen women had in-phase and 21 had out-of-phase LPD biopsies. Lipoprotein levels were obtained in a fasted state on the day of the luteal phase on which the biopsy was performed. No difference in covariates that affect lipoprotein levels such as obesity, age, and alcohol use were observed between the two groups. No significant differences between groups were found for triglycerides, total cholesterol, very low density lipoprotein, LDL, HDL, HDL2, and HDL3 concentrations. However, LPD was associated with a reduction in the extent to which: age and obesity are associated with higher triglycerides; obesity is associated with a lower HDL2; and alcohol is associated with a higher HDL3-cholesterol. Lipoproteins on average are not different in LPD, suggesting reasons other than a deficient plasma lipoprotein cholesterol source as the explanation for decreased P secretion. A lesser interaction between LDL or HDL and obesity, age, and alcohol in LPD could signify an influence of the altered hormonal milieu of LPD on the way lipoproteins interact with covariates and could lead to differences in lipoproteins between normal and LPD subjects at the extremes of the lipoprotein distribution.

Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers

PubMed Central

Chiquette, Elaine; Toth, Peter P; Ramirez, Gilbert; Cobble, Michael; Chilton, Robert

2012-01-01

Background Dyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials. Methods In the DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical auto profile methodology and the Statistical Package for the Social Sciences general linear model adjusted for glycosylated hemoglobin (HbA1c) and weight. Results Baseline lipids and high sensitivity C-reactive protein were normal overall based on the standard lipid panel. Once-weekly exenatide reduced apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05), independent of glycemic improvement and weight loss. A significant shift in lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol was also observed (P < 0.05). Exenatide once weekly increased high-density lipoprotein-2 cholesterol, even after adjustment for changes in HbA1c and weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and high sensitivity C-reactive protein were reduced with both the once-weekly and twice-daily exenatide regimens (P < 0.05). Conclusion In this post hoc analysis, exenatide significantly improved a number of cardiovascular risk markers. Continuous exenatide exposure with exenatide once weekly elicited a greater response than did immediate-release exenatide twice daily, generally independent of glycemic improvement and weight loss. Thus, in addition to improving glycemic control, exenatide induced favorable changes in lipid and lipoprotein metabolism and decreased systemic inflammation. PMID:23166441

Pim-1L Protects Cell Surface-Resident ABCA1 From Lysosomal Degradation in Hepatocytes and Thereby Regulates Plasma High-Density Lipoprotein Level.

PubMed

Katsube, Akira; Hayashi, Hisamitsu; Kusuhara, Hiroyuki

2016-12-01

ATP-binding cassette transporter A1 (ABCA1) exerts an atheroprotective action through the biogenesis of high-density lipoprotein in hepatocytes and prevents the formation of foam cells from macrophages. Controlling ABCA1 is a rational approach to improving atherosclerotic cardiovascular disease. Although much is known about the regulatory mechanism of ABCA1 synthesis, the molecular mechanism underpinning its degradation remains to be clearly described. ABCA1 possesses potential sites of phosphorylation by serine/threonine-protein kinase Pim-1 (Pim-1). Pim-1 depletion decreased the expression of cell surface-resident ABCA1 (csABCA1) and apolipoprotein A-I-mediated [ 3 H]cholesterol efflux in the human hepatoma cell line HepG2, but not in peritoneal macrophages from mice. In vitro kinase assay, immunoprecipitation, and immunocytochemistry suggested phosphorylation of csABCA1 by the long form of Pim-1 (Pim-1L). Cell surface biotinylation indicated that Pim-1L inhibited lysosomal degradation of csABCA1 involving the liver X receptor β, which interacts with csABCA1 and thereby protects it from ubiquitination and subsequent lysosomal degradation. Cell surface coimmunoprecipitation with COS-1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that Pim-1L-mediated phosphorylation of csABCA1 facilitated the interaction between csABCA1 and liver X receptor β and thereby stabilized the csABCA1-Pim-1L complex. Mice deficient in Pim-1 kinase activity showed lower expression of ABCA1 in liver plasma membranes and lower plasma high-density lipoprotein levels than control mice. Pim-1L protects hepatic csABCA1 from lysosomal degradation by facilitating the physical interaction between csABCA1 and liver X receptor β and subsequent stabilization of the csABCA1-Pim-1L complex and thereby regulates the circulating level of high-density lipoprotein. Our findings may aid the development of high-density lipoprotein-targeted therapy. © 2016 American Heart Association, Inc.

Effect of platelet activating factor on endothelial permeability to plasma macromolecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Handley, D.A.; Arbeeny, C.M.; Lee, M.L.

The effect of intrajugular administration of platelet activating factor (PAF-C16) on vascular permeability was examined in the guinea pig. To examine the loss of selective endothelial permeability, the extravasative effect of PAF was assessed by monitoring hemoconcentration and the plasma loss of /sup 125/I-albumin (6.7 nm), /sup 125/I-low density lipoproteins (22.0 nm) or /sup 125/I-very low density lipoproteins (62.1 nm). Extravasation was dose-dependent and began 1 min after PAF administration, continuing for 5-7 min. During extravasation, there was no evidence for selective plasma retention of any of the labeled plasma tracers, as measured by plasma radioactivity. These results suggest thatmore » PAF-induced extravasation is dose-dependent, with increases in vascular permeability sufficient to permit similar plasma efflux rates of albumin, low density lipoproteins and very low density lipoproteins.« less

The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention

PubMed Central

DePalma, Ralph G.; Shamayeva, Galina; Chow, Bruce K.

2013-01-01

Objectives. We postulated the existence of a statin–iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores. Methods. Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins. Results. Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status. Conclusions. There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins. PMID:23409890

Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic

DTIC Science & Technology

2008-12-01

statistically significant. T. Chol indicates total cholesterol ; HDL, high - density lipoprotein . B, Hematoxylin and eosin staining of proximal aortas from...low density lipoprotein receptor null Ldlr/ mice transplanted with Stat1/ bone marrow. Conclusions—STAT1 is critical for endoplasmic reticulum...intracellular accumulation of lipoprotein - derived free cholesterol (FC).11 FC enrichment of macro- phages, like many ER stressors, activates the UPR

Cholesterol in serum lipoprotein fractions after spaceflight

NASA Technical Reports Server (NTRS)

Leach, Carolyn S.; Johnson, Philip C., Jr.; Krauhs, Jane M.; Cintron, Nitza M.

1988-01-01

Results are reported from blood-lipid measurements obtained from 125 Space Shuttle crew members before and after space flight. The data are presented in tables and discussed in detail. The main differences noted between preflight and postflight values are a 12.8-percent decrease in high-density lipoproteins on postflight day 1 and significant decreases in total cholesterol and both high- and low-density lipoproteins later in the 23-day postflight period.

Effect of dietary fat source on lipoprotein composition and plasma lipid concentrations in pigs.

PubMed

Faidley, T D; Luhman, C M; Galloway, S T; Foley, M K; Beitz, D C

1990-10-01

Most studies of the effects of dietary fat sources on plasma lipid components have used diets with extreme fat compositions; the current study was designed to more nearly mimic human dietary fat intake. Young growing pigs were fed diets containing either 20 or 40% of energy as soy oil, beef tallow or a 50/50 blend of soy oil and tallow. Different dietary fats did not affect concentrations of cholesterol, triacylglycerol or protein in plasma or major lipoprotein fractions. The concentration of phospholipid was less in plasma and in very low density lipoproteins with soy oil feeding than with tallow feeding. The weight percentage of cholesteryl ester in the low density lipoprotein fraction tended to be greater with 40% than with 20% tallow and tended to be less with 40% than with 20% soy oil. Phospholipid as a weight percentage of low density lipoprotein was least in pigs fed soy oil. Tallow feeding increased the percentage of myristic, palmitic, palmitoleic and oleic acids in plasma, relative to both other groups. Soy oil feeding increased the percentage of linoleic and linolenic acids. These moderate diets were not hypercholesterolemic, but they did alter plasma fatty acid composition and phospholipid concentrations in plasma and very low density lipoprotein.

Apolipoprotein E3 Mediated Targeted Brain Delivery of Reconstituted High Density Lipoprotein Bearing 3, 10, And 17 Nm Hydrophobic Core Gold Nanoparticles

NASA Astrophysics Data System (ADS)

Chuang, Skylar T.

We have developed a high density lipoprotein (HDL)-based platform for transport and delivery of hydrophobic gold nanoparticles (AuNP). The ability of apolipoprotein E3 (apoE3) to act as a ligand for the low-density lipoprotein receptor (LDLr) was exploited to gain entry of HDL with AuNP into glioblastoma cells. AuNP of 3, 10 and 17 nm diameter, the latter two synthesized by phase transfer process, were solubilized by integration into reconstituted HDL (rHDL). Absorption spectroscopy indicated the presence of stable particles with signature surface plasmon bands, while electron microscopy revealed AuNP embedded in rHDL core. The rHDL-AuNP complexes displayed robust binding to the LDLr, were internalized by the glioblastoma cells, and appeared as aggregated AuNP in the endosomal-lysosomal compartments. The rHDL-AuNP generated little cytotoxicity and were able to cross the blood brain barrier. The findings bear significance since they offer an effective means of delivering AuNP across tumor cell membrane.

Serum high density lipoprotein cholesterol, alcohol, and coronary mortality in male smokers.

PubMed Central

Paunio, M.; Virtamo, J.; Gref, C. G.; Heinonen, O. P.

1996-01-01

OBJECTIVE--To determine whether the increase in mortality from coronary heart disease with high concentration (> 1.75 mmol/l) of high density lipoprotein cholesterol could be due to alcohol intake. DESIGN--Cohort study. SETTING--Placebo group of the alpha tocopherol, beta carotene cancer prevention (ATBC) study of south western population in Finland. PARTICIPANTS--7052 male smokers aged 50-69 years enrolled to the ATBC study in the 1980s. MAIN OUTCOME MEASURES--The relative and absolute rates adjusted for risk factors for clinically or pathologically verified deaths from coronary heart disease for different concentrations of high density lipoprotein cholesterol with and without stratification for alcohol intake. Similar rates were also calculated for different alcohol consumption groups. RESULTS--During the average follow up period of 6.7 years 258 men died from verified coronary heart disease. Coronary death rate steadily decreased with increasing concentration of high density lipoprotein cholesterol until a high concentration. An increase in the rate was observed above 1.75 mmol/l. This increase occurred among those who reported alcohol intake. Mortality was associated with alcohol intake in a J shaped dose response, and those who reported consuming more than five drinks a day (heavy drinkers) had the highest death rate. Mortality was higher in heavy drinkers than in non-drinkers or light or moderate drinkers in all high density lipoprotein categories from 0.91 mmol/l upward. CONCLUSIONS--Mortality from coronary heart disease increases at concentrations of high density lipoprotein cholesterol over 1.75 mmol/l. The mortality was highest among heavy drinkers, but an increase was found among light drinkers also. PMID:8634563

Collagenase-3 binds to a specific receptor and requires the low density lipoprotein receptor-related protein for internalization

NASA Technical Reports Server (NTRS)

Barmina, O. Y.; Walling, H. W.; Fiacco, G. J.; Freije, J. M.; Lopez-Otin, C.; Jeffrey, J. J.; Partridge, N. C.

1999-01-01

We have previously identified a specific receptor for collagenase-3 that mediates the binding, internalization, and degradation of this ligand in UMR 106-01 rat osteoblastic osteosarcoma cells. In the present study, we show that collagenase-3 binding is calcium-dependent and occurs in a variety of cell types, including osteoblastic and fibroblastic cells. We also present evidence supporting a two-step mechanism of collagenase-3 binding and internalization involving both a specific collagenase-3 receptor and the low density lipoprotein receptor-related protein. Ligand blot analysis shows that (125)I-collagenase-3 binds specifically to two proteins ( approximately 170 kDa and approximately 600 kDa) present in UMR 106-01 cells. Western blotting identified the 600-kDa protein as the low density lipoprotein receptor-related protein. Our data suggest that the 170-kDa protein is a specific collagenase-3 receptor. Low density lipoprotein receptor-related protein-null mouse embryo fibroblasts bind but fail to internalize collagenase-3, whereas UMR 106-01 and wild-type mouse embryo fibroblasts bind and internalize collagenase-3. Internalization, but not binding, is inhibited by the 39-kDa receptor-associated protein. We conclude that the internalization of collagenase-3 requires the participation of the low density lipoprotein receptor-related protein and propose a model in which the cell surface interaction of this ligand requires a sequential contribution from two receptors, with the collagenase-3 receptor acting as a high affinity primary binding site and the low density lipoprotein receptor-related protein mediating internalization.

Statins.

PubMed

Skinner, Anita

2014-08-26

While I was aware of the link between high serum cholesterol and cardiovascular disease, I was unaware of the mechanism of atheroma development. The CPD article discussed the role of low-density lipoprotein in the development of atherosclerosis, which I found very interesting.

Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

PubMed

Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

2015-05-01

Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

PubMed

Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

2015-08-01

Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27-2.50 per SD increase in ApoC-III; P<0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM. © 2015 American Heart Association, Inc.

Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome.

PubMed

Olson, Eric J; Pearce, Gregory L; Jones, Nigel P; Sprecher, Dennis L

2012-09-01

Peroxisome proliferator-activated receptor-δ-induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins. GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol <1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (-7.3%), triglycerides (-16.9%), apoB (-14.9%), and free fatty acids (-19.4%). The exploratory study showed significant reductions in the concentration of very LDL (-19%), intermediate-density lipoprotein (-52%), and LDL (-14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL). GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor-δ being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.

Thermal transitions in the low-density lipoprotein and lipids of the egg yolk of hens.

PubMed

Smith, M B; Back, J F

1975-05-22

1. Differential sanning calorimetry and light-scattering have been used to investigate temperature-dependent transitions in low-density lipoprotein and in lipids from hens' egg yolk. Yolks of different fatty acid composition were obtained by varying the dietary lipid and by adding methyl sterculate to the hen's diet. 2. Lipoprotein solutions in 50 percent glycerol/water gave characteristic melting curves between -25 degrees C and 50 degrees C, and on cooling showed increases in light-scattering between 10 degrees C and -20 degrees C. The temperatures at which major changes occurred depended on the proportions of saturated and unsaturated fatty acids. 3. The thermal transitions in the intact lipoprotein in glycerol solution were reversible, but with marked hysteresis. Lipid extracted from the lipoprotein did not show temperature hystersis but the transition heats and melting curves similar to those of the intact lipoprotein. The results support the hypothesis of a "lipid-core" structure for low-density lipoproteins. 4. Scanning calorimetry of egg-yolk lecithins indicated a strong dependence of transition temperature on water content in the rane 3 percent-20 percent water. A rise in the mid-temperature of the liquid-crystalline to gel transition as the water content is lowered on freezing may be the primary event in the irreversible gelation of egg yolk and aggregation of lipoprotein.

Balancing Low-density Lipoprotein Cholesterol Reduction and Hepatotoxicity With Lomitapide Mesylate and Mipomersen in Patients With Homozygous Familial Hypercholesterolemia.

PubMed

Won, Jane I; Zhang, Jun; Tecson, Kristen M; McCullough, Peter A

2017-01-01

Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant disorder manifested by high concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in patients with HoFH; these patients are considered to be at high risk for cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action were approved by the US Food and Drug Administration for the treatment of HoFH: lomitapide mesylate and mipomersen. Both of these treatments reduce total cholesterol, LDL cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein a, and triglyceride levels. This review describes the clinical tradeoffs in efficacy and hepatotoxicity of these drugs in two cases of HoFH.

Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake.

PubMed

Friday, K E; Drinkwater, B L; Bruemmer, B; Chesnut, C; Chait, A

1993-12-01

To determine the interactive effects of hormones, exercise, and diet on plasma lipids and lipoproteins, serum estrogen and progesterone levels, nutrient intake, and plasma lipid, lipoprotein, and apolipoprotein concentrations were measured in 24 hypoestrogenic amenorrheic and 44 eumenorrheic female athletes. When compared to eumenorrheic athletes, amenorrheic athletes had higher levels of plasma cholesterol (5.47 +/- 0.17 vs. 4.84 +/- 0.12 mmol/L, P = 0.003), triglyceride (0.75 +/- 0.06 vs. 0.61 +/- 0.03 mmol/L, P = 0.046), low-density lipoprotein (LDL; 3.16 +/- 0.15 vs. 2.81 +/- 0.09 mmol/L, P = 0.037), high-density lipoprotein (HDL; 1.95 +/- 0.07 vs. 1.73 +/- 0.05 mmol/L, P = 0.007), and HDL2 (0.84 +/- 0.06 vs. 0.68 +/- 0.04 mmol/L, P = 0.02) cholesterol. Plasma LDL/HDL cholesterol ratios, very low-density lipoprotein and HDL3 cholesterol, and apolipoprotein A-I and A-II levels were similar in the two groups. Amenorrheic athletes consumed less fat than eumenorrheic subjects (52 +/- 5 vs. 75 +/- 3 g/day, P = 0.02), but similar amounts of calories, cholesterol, protein, carbohydrate, and ethanol. HDL cholesterol levels in amenorrheic subjects correlated positively with the percent of dietary calories from fat (r = 0.42, n = 23, P = 0.045) but negatively with the percent from protein (r = -0.49, n = 23, P = 0.017). Thus, exercise-induced amenorrhea may adversely affect cardiovascular risk by increasing plasma LDL and total cholesterol. However, cardioprotective elevations in plasma HDL and HDL2 cholesterol may neutralize the risk of cardiovascular disease in amenorrheic athletes.

[Pathogenic mechanisms of proatherogenic changes in pregnant women with concomitant obesity].

PubMed

Tarasenko, K V; Mamontova, T V

2013-12-01

The concentration of insulin, high sensitivity C-reactive protein (CRP) and indices of lipid metabolism (concentrations of triacylglycerols, total cholesterol, cholesterol of low density lipoproteins and cholesterol of very low density lipoproteins) in women with concomitant obesity in the second trimester of pregnancy were studied. Changes of the lipid profile in the pregnant women with concomitant obesity indicate development of type IV hyperlipoproteinemia. Concentrations of insulin and CRP in the blood serum of the pregnant women with obesity were respectively 92.1% and 62.5% higher than in the control group. On the basis of literature data and our own research it was concluded that the complex of the metabolic changes (insulin resistance, dislipidemia, endothelial dysfunction, systemic inflammation) in pregnant women with obesity promotes development of proatherogenic changes.

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

PubMed

Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

2017-03-01

Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

Recent Advances in Fluorescent Angioscopy for Molecular Imaging of Human Atherosclerotic Coronary Plaque

PubMed Central

2017-01-01

Purpose of Review: In vivo imaging of the native substances, including lipoproteins, that comprise human atherosclerotic plaques is currently beyond the scope of any available imaging techniques. Color and near-infrared fluorescent angioscopy (CFA and NIRFA, respectively) systems have been recently developed for molecular imaging of lipoproteins within the human coronary arterial wall ex vivo and/or in vivo. The author reviews recent findings on lipoprotein deposition in human coronary plaques obtained by these imaging techniques. Recent Findings: Using specific biomarkers, native pro-atherogenic substances such as oxidized low-density lipoprotein (ox-LDL), LDL, triglycerides (TG), apolipoprotein B-100 (ApoB-100), and lysophosphatidylcholine (LPC), and the anti-atherogenic substance such as high-density lipoprotein (HDL) were visualized by CFA, and LDL and cholesterol by NIRFA, in coronary plaques obtained from autopsy subjects. The relationship between incidence and plaque morphology differed for each substance. The incidence of ox-LDL and LDL on color fluorescence microscopy correlated well with that observed using immunohistochemical techniques. During coronary catheterization in patients, ox-LDL, LDL, and HDL in coronary plaques were visualized by CFA or NIRFA. Conclusions: Using CFA or NIRFA, the distribution of the major native pro-atherogenic and antiatherogenic lipoproteins and their components within human coronary plaques can be evaluated ex vivo and/or in vivo. Fluorescent angioscopy could help our understanding of the molecular mechanisms of coronary atherosclerosis and in the evaluation of the effects of therapy targeting the substances comprising atherosclerotic coronary plaques. PMID:28381766

Effects of the Particulate Matter₂.₅ (PM₂.₅) on Lipoprotein Metabolism, Uptake and Degradation, and Embryo Toxicity.

PubMed

Kim, Jae-Yong; Lee, Eun-Young; Choi, Inho; Kim, Jihoe; Cho, Kyung-Hyun

2015-12-01

Particulate matter2.5 (PM2.5) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which PM2.5 aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous PM2.5 solution on lipoprotein metabolism. Collected PM2.5 from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. PM2.5 extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. PM2.5 treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by PM2.5 solution in a dose-dependent manner. Further, PM2.5 solution caused cellular senescence in human dermal fibroblast cells. Microinjection of PM2.5 solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of PM2.5 induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins.

Effects of the Particulate Matter2.5 (PM2.5) on Lipoprotein Metabolism, Uptake and Degradation, and Embryo Toxicity

PubMed Central

Kim, Jae-Yong; Lee, Eun-Young; Choi, Inho; Kim, Jihoe; Cho, Kyung-Hyun

2015-01-01

Particulate matter2.5 (PM2.5) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which PM2.5 aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous PM2.5 solution on lipoprotein metabolism. Collected PM2.5 from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. PM2.5 extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. PM2.5 treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by PM2.5 solution in a dose-dependent manner. Further, PM2.5 solution caused cellular senescence in human dermal fibroblast cells. Microinjection of PM2.5 solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of PM2.5 induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins. PMID:26615830

Status of non-HDL-cholesterol and LDL-cholesterol among subjects with and without metabolic syndrome.

PubMed

Khan, Sikandar Hayat; Asif, Naveed; Ijaz, Aamir; Manzoor, Syed Mohsin; Niazi, Najumusaquib Khan; Fazal, Nadeem

2018-04-01

To to compare non-high-density lipoprotein and low-density lipoprotein cholesterol among subjects with or without metabolic syndrome, glycation status and nephropathic changes. The comparative cross-sectional study was carried out from Dec 21, 2015, to Nov 15, 2016, at the department of pathology and medicine PNS HAFEEZ and department of chemical pathology and clinical endocrinology (AFIP), and comprised patients of either gender visiting the out-patient department for routine screening. They were evaluated for anthropometric indices, blood pressure and sampled for lipid profile, fasting plasma glucose, glycated haemoglobin, insulin, and urine albumin-to-creatinine ratio. Subjects were segregated based upon presence (Group1) or absence (Group2) of metabolic syndrome based upon criteria of National Cholesterol Education Programme and the International Diabetes Federation. Differences in high and low density lipoprotein cholesterols were calculated between the groups. Of the 229 subjects, 120(52.4%) were women and 109(47.6%) were men. Overall, there were 107(46.7%) subjects in Group 1, and 122(53.3%) in Group 2. Non-high-density lipoprotein cholesterol was significantly different between subjects with and without metabolic syndrome as per both the study criteria (p<0.05 each). . Non-high-density lipoprotein cholesterol levels were higher in subjects with metabolic syndrome.

Mechanism of action of a peroxisome proliferator-activated receptor (PPAR)-delta agonist on lipoprotein metabolism in dyslipidemic subjects with central obesity.

PubMed

Ooi, Esther M M; Watts, Gerald F; Sprecher, Dennis L; Chan, Dick C; Barrett, P Hugh R

2011-10-01

Dyslipidemia increases the risk of cardiovascular disease in obesity. Peroxisome proliferator-activated receptor (PPAR)-δ agonists decrease plasma triglycerides and increase high-density lipoprotein (HDL)-cholesterol in humans. The aim of the study was to examine the effect of GW501516, a PPAR-δ agonist, on lipoprotein metabolism. Design, Setting, and Intervention: We conducted a randomized, double-blind, crossover trial of 6-wk intervention periods with placebo or GW501516 (2.5 mg/d), with 2-wk placebo washout between treatment periods. We recruited 13 dyslipidemic men with central obesity from the general community. We measured the kinetics of very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein-, and low-density lipoprotein (LDL)-apolipoprotein (apo) B-100, plasma apoC-III, and high-density lipoprotein (HDL) particles (LpA-I and LpA-I:A-II). GW501516 decreased plasma triglycerides, fatty acid, apoB-100, and apoB-48 concentrations. GW501516 decreased the concentrations of VLDL-apoB by increasing its fractional catabolism and of apoC-III by decreasing its production rate (P < 0.05). GW501516 reduced VLDL-to-LDL conversion and LDL-apoB production. GW501516 increased HDL-cholesterol, apoA-II, and LpA-I:A-II concentrations by increasing apoA-II and LpA-I:A-II production (P < 0.05). GW501516 decreased cholesteryl ester transfer protein activity, and this was paralleled by falls in the triglyceride content of VLDL, LDL, and HDL and the cholesterol content of VLDL and LDL. GW501516 increased the hepatic removal of VLDL particles, which might have resulted from decreased apoC-III concentration. GW501516 increased apoA-II production, resulting in an increased concentration of LpA-I:A-II particles. This study elucidates the mechanism of action of this PPAR-δ agonist on lipoprotein metabolism and supports its potential use in treating dyslipidemia in obesity.

Longitudinal Changes in Cholesterol Efflux Capacities in Patients With Coronary Artery Disease Undergoing Lifestyle Modification Therapy.

PubMed

Boyer, Marjorie; Lévesque, Valérie; Poirier, Paul; Marette, André; Mitchell, Patricia L; Mora, Samia; Mathieu, Patrick; Després, Jean-Pierre; Larose, Éric; Arsenault, Benoit J

2018-06-01

Our objective was to identify the determinants of high-density lipoprotein cholesterol efflux capacity (HDL-CEC) changes in patients with coronary artery disease who participated in a lifestyle modification program aimed at increasing physical activity levels and improving diet quality. A total of 86 men with coronary artery disease aged between 35 and 80 years participated in a 1-year lifestyle modification program that aimed to achieve a minimum of 150 minutes of aerobic physical activity weekly and improve diet quality. HDL-CECs were measured before and after the 1-year intervention using 3 H-cholesterol-labeled J774 and HepG2 cells. Visceral, subcutaneous, and cardiac adipose tissue levels were assessed before and after the intervention using magnetic resonance imaging. Lipoprotein particle size and concentrations were measured by proton nuclear magnetic resonance spectroscopy and a complete lipoprotein-lipid profile was obtained. At baseline, the best correlate of HDL-CECs were apolipoprotein AI ( R 2 =0.35, P <0.0001) and high-density lipoprotein cholesterol ( R 2 =0.21, P <0.0001) for J774-HDL-CECs and HepG2-HDL-CECs, respectively. Baseline and longitudinal changes in HDL-CECs were associated with several lipoprotein size and concentration indices, although high-density lipoprotein cholesterol was the best predictor of longitudinal changes in J774-HDL-CECs ( R 2 =0.18, P =0.002) and apolipoprotein AI was found to be the best predictor of longitudinal changes in HepG2 cholesterol efflux capacities ( R 2 =0.21, P =0.002). Results of this study suggest that increases in high-density lipoprotein cholesterol and apolipoprotein AI levels typically observed in patients with coronary artery disease undergoing healthy lifestyle modification therapy may be indicative of higher plasma concentrations of functional high-density lipoprotein particles. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Lipoprotein lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

USDA-ARS?s Scientific Manuscript database

Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified gro...

Moderate alcohol consumption and changes in postprandial lipoproteins of premenopausal and postmenopausal women: a diet-controlled, randomized intervention study.

PubMed

van der Gaag, M S; Sierksma, A; Schaafsma, G; van Tol, A; Geelhoed-Mieras, T; Bakker, M; Hendriks, H F

2000-01-01

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Earlier studies in men have shown that moderate alcohol consumption affects lipoprotein metabolism and hemostasis. In this diet-controlled, randomized, crossover trial, we investigated the effect on lipoprotein metabolism of moderate consumption of red wine or red grape juice with evening dinner for 3 weeks in premenopausal women using oral contraceptives and in postmenopausal women. After 3 weeks, blood samples were collected 1 hour before dinner up to 19 hours after starting dinner at 2-hour or 4-hour intervals. Plasma triglyceride concentrations and very low density lipoprotein (VLDL) triglyceride levels peaked 3 hours after dinner with wine in both premenopausal and postmenopausal women. After wine consumption, the overall high-density lipoprotein (HDL) cholesterol level was increased in postmenopausal women (mean increase 0.17 mmol/L, or 12%, p = 0.03), and the plasma low-density lipoprotein (LDL) cholesterol level was reduced in premenopausal women (mean reduction 0.35 mmol/L, or 12%, p = 0.01) as compared with grape juice consumption. The findings suggest that postprandial lipoprotein metabolism after moderate alcohol consumption differs between oral contraceptive-using premenopausal women and postmenopausal women. The response of postmenopausal women to alcohol resembled the response found in earlier studies in men.

Polyphenols isolated from virgin coconut oil attenuate cadmium-induced dyslipidemia and oxidative stress due to their antioxidant properties and potential benefits on cardiovascular risk ratios in rats.

PubMed

Famurewa, Ademola Clement; Ejezie, Fidelis Ebele

2018-01-01

Literature has confirmed the pathogenic role of cadmium (Cd) and its exposure in the induction of dyslipidemia implicated in the development and increasing incidence of cardiovascular diseases. The current study explored whether polyphenolics isolated from virgin coconut oil (VCO) prevent Cd-induced dyslipidemia and investigate the underlying mechanism of action, in rats. Rats were pretreated with VCO polyphenols (10, 20 and 50 mg/kg body weight; orally) 2 weeks prior to concurrent Cd administration (5 mg/kg) for 5 weeks. Subsequently, serum concentrations of lipid and lipoprotein cholesterol and cardiovascular risk ratios were determined. Hepatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as reduced glutathione (GSH) and malondialdehyde (MDA) contents were analyzed. Sub-chronic Cd administration significantly increased the serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol while markedly reduced high density lipoprotein cholesterol. Hepatic activities of SOD and CAT as well as GSH content were suppressed by Cd, whereas MDA level was obviously increased. The co-administration of VCO polyphenol with Cd remarkably restored lipid profile and cardiovascular risk ratios and stabilized antioxidant defense systems comparable to control group. This is the first study presenting that polyphenols isolated from VCO prevent Cd-induced lipid abnormalities and cardiovascular risk ratios by improving antioxidant defense systems.

Regulation of plasma cholesterol by hepatic low-density lipoprotein receptors.

PubMed

Kovanen, P T

1987-02-01

The endogenous lipoprotein system (very low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL] cascade) holds the key to understanding the mechanisms by which hormones, diet, and drugs interact to regulate the plasma cholesterol level. Crucial components of this system are hepatic LDL receptors that mediate the uptake and degradation of plasma LDL. With experimental animals, it has been possible to demonstrate that hepatic LDL receptors are sensitive to hormonal, dietary, and pharmacologic manipulation. The decrease in number of hepatic LDL receptors in hypothyroidism or after cholesterol feeding leads to elevation of plasma LDL cholesterol levels. Conversely, the increase in number of hepatic LDL receptors results in lowering of plasma LDL cholesterol levels. This can be observed in hyperthyroidism, during administration of pharmacologic doses of 17 alpha-ethinyl estradiol, or during treatment with cholesterol-lowering drugs such as the bile acid-binding resins and cholesterol-synthesis inhibitors. Since cholesterol excretion from the body occurs via the liver, the increased efficiency of disposal of plasma cholesterol by increasing hepatic LDL receptors will ultimately lead to depletion of excessive body cholesterol. Pharmacologic regulation of hepatic LDL receptors should be a valuable tool in the prevention and therapy of atherosclerosis.

Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus.

PubMed

Gutierrez, Maria J; Rosenberg, Noah L; Macdougall, Diane E; Hanselman, Jeffrey C; Margulies, Janice R; Strange, Poul; Milad, Mark A; McBride, Scott J; Newton, Roger S

2014-03-01

8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid (ETC-1002) is a small molecule with a unique mechanism of action shown in nonclinical studies to modulate pathways of cholesterol, fatty acid, and carbohydrate metabolism. In previous phase 2 clinical trials, once daily oral treatment with ETC-1002 significantly reduced low-density lipoprotein-cholesterol in patients with hypercholesterolemia. In this trial, the lipid-lowering efficacy of ETC-1002 was evaluated in patients with type 2 diabetes mellitus and hypercholesterolemia. Additional cardiometabolic biomarkers, including glycemic measures, were also assessed. A single-center, double-blind, placebo-controlled trial evaluated 60 patients with type 2 diabetes mellitus and elevated low-density lipoprotein-cholesterol. Patients discontinued all diabetes mellitus and lipid-regulating drugs and were randomized to receive ETC-1002 80 mg QD for 2 weeks followed by 120 mg QD for 2 weeks or placebo for 4 weeks. ETC-1002 lowered low-density lipoprotein-cholesterol levels by 43±2.6% (least squares mean±SE), compared with a reduction of 4±2.5% by placebo at day 29 (P<0.0001; primary end point). Non-high-density lipoprotein-cholesterol and total cholesterol were also significantly lowered by ETC-1002 compared with placebo (P<0.0001). High-sensitivity C-reactive protein was reduced by 41% (median) compared with a placebo reduction of 11% (P=0.0011). No clinically meaningful safety findings were observed. ETC-1002 lowered low-density lipoprotein-cholesterol and other lipids and demonstrated improvement in high-sensitivity C-reactive protein in patients with type 2 diabetes mellitus and hypercholesterolemia without worsening glycemic control. ETC-1002 was well tolerated in this population. http://www.clinicaltrials.gov. Unique identifier: NCT# 01607294.

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial.

PubMed

Chinwong, Surarong; Chinwong, Dujrudee; Mangklabruks, Ampica

2017-01-01

This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO) consumption on plasma lipoproteins levels and adverse events. The study population was 35 healthy Thai volunteers, aged 18-25. At entry, participants were randomly allocated to receive either (i) 15 mL VCO or (ii) 15 mL 2% carboxymethylcellulose (CMC) solution (as control), twice daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits. Results . Of 32 volunteers with complete follow-up (16 males and 16 females), daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72 mg/dL ( p = 0.001) compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion . Daily consumption of 30 mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported.

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial

PubMed Central

2017-01-01

This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO) consumption on plasma lipoproteins levels and adverse events. The study population was 35 healthy Thai volunteers, aged 18–25. At entry, participants were randomly allocated to receive either (i) 15 mL VCO or (ii) 15 mL 2% carboxymethylcellulose (CMC) solution (as control), twice daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits. Results. Of 32 volunteers with complete follow-up (16 males and 16 females), daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72 mg/dL (p = 0.001) compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion. Daily consumption of 30 mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported. PMID:29387131

Distribution and Kinetics of Lipoprotein-Bound Lipoteichoic Acid

PubMed Central

Levels, Johannes H. M.; Abraham, Philip R.; van Barreveld, Erik P.; Meijers, Joost C. M.; van Deventer, Sander J. H.

2003-01-01

Lipoteichoic acid (LTA), a major cell wall component of gram-positive bacteria, is an amphipathic anionic glycolipid with structural similarities to lipopolysaccharide (LPS) from gram-negative bacteria. LTA has been implicated as one of the primary immunostimulatory components that may trigger the systemic inflammatory response syndrome. Plasma lipoproteins have been shown to sequester LPS, which results in attenuation of the host response to infection, but little is known about the LTA binding characteristics of plasma lipid particles. In this study, we have examined the LTA binding capacities and association kinetics of the major lipoprotein classes under simulated physiological conditions in human whole blood (ex vivo) by using biologically active, fluorescently labeled LTA and high-performance gel permeation chromatography. The average distribution of an LTA preparation from Staphylococcus aureus in whole blood from 10 human volunteers revealed that >95% of the LTA was associated with total plasma lipoproteins in the following proportions: high-density lipoprotein (HDL), 68% ± 10%; low-density lipoprotein (LDL), 28% ± 8%; and very low density lipoprotein (VLDL), 4% ± 5%. The saturation capacity of lipoproteins for LTA was in excess of 150 μg/ml. The LTA distribution was temperature dependent, with an optimal binding between 22 and 37°C. The binding of LTA by lipoproteins was essentially complete within 10 min and was followed by a subsequent redistribution from HDL and VLDL to LDL. We conclude that HDL has the highest binding capacity for LTA and propose that the loading and redistribution of LTA among plasma lipoproteins is a specific process that closely resembles that previously described for LPS (J. H. M. Levels, P. R. Abraham, A. van den Ende, and S. J. H. van Deventer, Infect. Immun. 68:2821-2828, 2001). PMID:12761109

Long-term Low-density Lipoprotein Apheresis in a Patient with Refractory Idiopathic Membranous Glomerulonephritis.

PubMed

Yabuuchi, Junko; Suwabe, Tatsuya; Mizuno, Hiroki; Ueno, Toshiharu; Hoshino, Junichi; Sekine, Akinari; Kawada, Masahiro; Yamanouchi, Masayuki; Hayami, Noriko; Hiramatsu, Rikako; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Fujii, Takeshi; Ohashi, Kenichi; Ubara, Yoshifumi

2017-01-01

A 61-year-old Japanese man developed nephrotic syndrome (NS) due to idiopathic membranous glomerulonephritis (MGN). He received immunosuppressive therapy for two years, including prednisolone, cyclophosphamide, and cyclosporine A, but the NS persisted. Low-density lipoprotein apheresis (LDL-A) was initiated at a frequency of twice a month and continued for 9 years (203 sessions in total). His proteinuria reduced to less than 1 g daily after 9 years. LDL-A was stopped, and the NS has not relapsed for five years. This case suggests that long-term LDL-A therapy may be a treatment option for idiopathic MGN refractory to immunosuppressive therapy or short-term LDL-A.

HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.

PubMed

Kotler, Donald P

2008-09-01

It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

A prominent large high-density lipoprotein at birth enriched in apolipoprotein C-I identifies a new group of infancts of lower birth weight and younger gestational age

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.

2003-10-01

Because low birth weight is associated with adverse cardiovascular risk and death in adults, lipoprotein heterogeneity at birth was studied. A prominent, large high-density lipoprotein (HDL) subclass enriched in apolipoprotein C-I (apoC-I) was found in 19 percent of infants, who had significantly lower birth weights and younger gestational ages and distinctly different lipoprotein profiles than infants with undetectable, possible or probable amounts of apoC-I-enriched HDL. An elevated amount of an apoC-I-enriched HDL identifies a new group of low birth weight infants.

Attenuated associations between increasing BMI and unfavorable lipid profiles in Chinese Buddhist vegetarians.

PubMed

Zhang, Hui-Jie; Han, Peng; Sun, Su-Yun; Wang, Li-Ying; Yan, Bing; Zhang, Jin-Hua; Zhang, Wei; Yang, Shu-Yu; Li, Xue-Jun

2013-01-01

Obesity is related to hyperlipidemia and risk of cardiovascular disease. Health benefits of vegetarian diets have well-documented in the Western countries where both obesity and hyperlipidemia were prevalent. We studied the association between BMI and various lipid/lipoprotein measures, as well as between BMI and predicted coronary heart disease probability in lean, low risk populations in Southern China. The study included 170 Buddhist monks (vegetarians) and 126 omnivore men. Interaction between BMI and vegetarian status was tested in the multivariable regression analysis adjusting for age, education, smoking, alcohol drinking, and physical activity. Compared with omnivores, vegetarians had significantly lower mean BMI, blood pressures, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, total cholesterol to high density lipoprotein ratio, triglycerides, apolipoprotein B and A-I, as well as lower predicted probability of coronary heart disease. Higher BMI was associated with unfavorable lipid/lipoprotein profile and predicted probability of coronary heart disease in both vegetarians and omnivores. However, the associations were significantly diminished in Buddhist vegetarians. Vegetarian diets not only lower BMI, but also attenuate the BMI-related increases of atherogenic lipid/ lipoprotein and the probability of coronary heart disease.

Lipoprotein Particle Concentrations May Explain the Absence of Coronary Protection in the Women's Health Initiative Hormone Trials

PubMed Central

Hsia, Judith; Otvos, James D.; Rossouw, Jacques E.; Wu, LieLing; Wassertheil-Smoller, Sylvia; Hendrix, Susan L.; Robinson, Jennifer G.; Lund, Bernedine; Kuller, Lewis H.

2009-01-01

Objective The Women's Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case–control substudy. Methods and Results We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo, and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls. Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001 versus placebo). In contrast, neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration (LDL-P). Conclusions Postmenopausal hormone therapy–induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the randomized hormone trials. PMID:18599797

Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

PubMed

Rysz-Górzyńska, Magdalena; Banach, Maciej

2016-08-01

A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

[Effect of treatment with selenium electrophoresis on biochemical indices in patients suffering from ischaemic cardiac disease with a stable stenocardia of tension].

PubMed

Kurtsikidze, I

2006-08-01

Disturbances in lipid metabolism, intensification of lipid peroxidize oxidation and functions of sympatho-adrenal system play an important role in the development and progressing of ischaemic cardiac disease. As a result of investigations it has been established that microelement--selenium has an antiatherogenic action and suppresses peroxidize oxidation of lipids. The effect of treatment with selenium electrophoresis in patients suffering from ischaemic cardiac disease with a stable stenocardia of tension has been studied. Total of 76 patients with ICS:SST of I-II functional classes (FC) have been investigated. It has been established that treatment with selenium electrophoresis provokes a reduction of overall cholesterol, triglycerides and beta-lipoproteins content in blood serum, as well as a decrease of cholesterol amount in beta-lipoproteins, lipoproteins of low and very low density and diene conjugates in blood serum and adrenaline and norepinephrine excretion with urine; increase of lipoprotein amount of high density in blood serum, activity of catalase and selenium excretion with urine. Above-said positive changes in biochemical data were more pronounced for the ICS:SST of the first FC.

Common variants at 30 loci contribute to polygenic dyslipidemia

USDA-ARS?s Scientific Manuscript database

Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to ...

Lack of effect of dietary fiber on serum lipids, glucose, and insulin in healthy young men fed high starch diets.

PubMed

Ullrich, I H; Albrink, M J

1982-07-01

Eight healthy young men were fed a 72% carbohydrate high starch diet either high or low in dietary fiber for 4 days in a double cross-over design. Both groups showed a slight transient increase in plasma triglyceride level and a decrease in total and high-density lipoprotein cholesterol. There were few differences in glucose and insulin levels after glucose and meal tolerance tests after each diet. Fasting triglycerides and high-density lipoprotein cholesterol were inversely related at base-line; insulin response to oral glucose was inversely related to high-density lipoprotein cholesterol levels at the end of the study. We conclude that a high carbohydrate high starch diet, whether high or low in fiber, caused little increase in triglycerides, with little difference between the high and low fiber diets. Dietary fiber did not influence the fall in plasma cholesterol or high-density lipoprotein cholesterol concentrations over and above that seen after the low fiber diet.

Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

NASA Astrophysics Data System (ADS)

Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

2016-04-01

Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

Activation of milk lipase by serum proteins: possible role in the occurrence of lipolysis in raw bovine milk.

PubMed

Clegg, R A

1980-02-01

The increase in unesterified fatty acid content of unpasteurized bulk milk in storage at 4 degrees C in the presence of known effectors of bovine milk lipoprotein lipase originating from bovine serum was studied. Bovine serum and high density lipoprotein (HDL) caused an increase in developed unesterified fatty acid levels whilst lipoprotein-free serum, apo-HDL, all individual apo-HDL tested, and the unfractionated C-peptide fraction were without lipolytic effect. In the presence of HDL-lipids, 2 C-peptides stimulated considerable lipolysis, as did the combination of HDL-lipid with unfractionated C-peptides. These characteristics of unesterified fatty acid development could be duplicated in milk whose endogenous lipolytic activity had been destroyed by heat treatment (75 degrees C for 5 min) and then restored by addition of purified bovine milk lipoprotein lipase. Radioactively labelled glycerol trioleate in milk was not hydrolysed in the same way as milk fat on the addition of serum liproproteins.

Exercise effects on lipids in persons with varying dietary patterns-does diet matter if they exercise? Responses in Studies of a Targeted Risk Reduction Intervention through Defined Exercise I.

PubMed

Huffman, Kim M; Hawk, Victoria H; Henes, Sarah T; Ocampo, Christine I; Orenduff, Melissa C; Slentz, Cris A; Johnson, Johanna L; Houmard, Joseph A; Samsa, Gregory P; Kraus, William E; Bales, Connie W

2012-07-01

The standard clinical approach for reducing cardiovascular disease risk due to dyslipidemia is to prescribe changes in diet and physical activity. The purpose of the current study was to determine if, across a range of dietary patterns, there were variable lipoprotein responses to an aerobic exercise training intervention. Subjects were participants in the STRRIDE I, a supervised exercise program in sedentary, overweight subjects randomized to 6 months of inactivity or 1 of 3 aerobic exercise programs. To characterize diet patterns observed during the study, we calculated a modified z-score that included intakes of total fat, saturated fat, trans fatty acids, cholesterol, omega-3 fatty acids, and fiber as compared with the 2006 American Heart Association diet recommendations. Linear models were used to evaluate relationships between diet patterns and exercise effects on lipoproteins/lipids. Independent of diet, exercise had beneficial effects on low-density lipoprotein cholesterol particle number, low-density lipoprotein cholesterol size, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol size, and triglycerides (P < .05 for all). However, having a diet pattern that closely adhered to American Heart Association recommendations was not related to changes in these or any other serum lipids or lipoproteins in any of the exercise groups. We found that even in sedentary individuals whose habitual diets vary in the extent of adherence to AHA dietary recommendations, a rigorous, supervised exercise intervention can achieve significant beneficial lipid effects. Copyright © 2012 Mosby, Inc. All rights reserved.

[Methodological aspects of evaluation of potential lipid capacity for peroxidation from the serum levels of TBA-active products during iron ion stimulation].

PubMed

Kulikova, A I; Tugusheva, F A; Zubina, I M; Shepilova, I N

2008-05-01

The authors propose a simple and reproducible procedure for using iron ions to stimulate serum lipid peroxidation, with TBA-active products being further determined. The procedure determines the reserve of lipids that can be oxidized during oxidative stress. A combination of direct studies and correlation analysis suggests that low-density lipoproteins and very low-density lipoproteins are the major substrates for lipid peroxidation while high-density lipoproteins show a high resistance to this process. The presented procedure may be used to monitor lipid peroxidation in various conditions and upon various exposures in common laboratory practice.

Relationship Between Changes in Serum Thyrotropin and Total and Lipoprotein Cholesterol with Prolonged Antarctic Residence

DTIC Science & Technology

1993-09-01

density lipoprotein ( HDL -C) cholesterol and triglyceride changes in TSH (P < .05)1 TBG (P < .01), TT3 (P < .05), ( TG ), on the other hand, were analyzed from...total thyroxine (TT4), free T4 (FT4), total T3 (TT3), free T3 (FT3), thyroid-binding globulin (TBG), total cholesterol (T-CHOL), high - density lipoprotein ... cholesterol ( HDL -C), triglyceride ( TG ), dietary cholesterol (D-CHOL), dietary fat (D-FAT), and dietary

Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholest...

Very-Low-Density Lipoprotein (VLDL)-Producing and Hepatitis C Virus-Replicating HepG2 Cells Secrete No More Lipoviroparticles than VLDL-Deficient Huh7.5 Cells

PubMed Central

Jammart, Baptiste; Michelet, Maud; Pécheur, Eve-Isabelle; Parent, Romain; Bartosch, Birke; Zoulim, Fabien

2013-01-01

In the plasma samples of hepatitis C virus (HCV)-infected patients, lipoviroparticles (LVPs), defined as (very-) low-density viral particles immunoprecipitated with anti-β-lipoproteins antibodies are observed. This HCV-lipoprotein association has major implications with respect to our understanding of HCV assembly, secretion, and entry. However, cell culture-grown HCV (HCVcc) virions produced in Huh7 cells, which are deficient for very-low-density lipoprotein (VLDL) secretion, are only associated with and dependent on apolipoprotein E (apoE), not apolipoprotein B (apoB), for assembly and infectivity. In contrast to Huh7, HepG2 cells can be stimulated to produce VLDL by both oleic acid treatment and inhibition of the MEK/extracellular signal-regulated kinase (ERK) pathway but are not permissive for persistent HCV replication. Here, we developed a new HCV cell culture model to study the interaction between HCV and lipoproteins, based on engineered HepG2 cells stably replicating a blasticidin-tagged HCV JFH1 strain (JB). Control Huh7.5-JB as well as HepG2-JB cell lines persistently replicated viral RNA and expressed viral proteins with a subcellular colocalization of double-stranded RNA (dsRNA), core, gpE2, and NS5A compatible with virion assembly. The intracellular RNA replication level was increased in HepG2-JB cells upon dimethyl sulfoxide (DMSO) treatment, MEK/ERK inhibition, and NS5A overexpression to a level similar to that observed in Huh7.5-JB cells. Both cell culture systems produced infectious virions, which were surprisingly biophysically and biochemically similar. They floated at similar densities on gradients, contained mainly apoE but not apoB, and were not neutralized by anti-apoB antibodies. This suggests that there is no correlation between the ability of cells to simultaneously replicate HCV as well as secrete VLDL and their capacity to produce LVPs. PMID:23427158

Very-low-density lipoprotein (VLDL)-producing and hepatitis C virus-replicating HepG2 cells secrete no more lipoviroparticles than VLDL-deficient Huh7.5 cells.

PubMed

Jammart, Baptiste; Michelet, Maud; Pécheur, Eve-Isabelle; Parent, Romain; Bartosch, Birke; Zoulim, Fabien; Durantel, David

2013-05-01

In the plasma samples of hepatitis C virus (HCV)-infected patients, lipoviroparticles (LVPs), defined as (very-) low-density viral particles immunoprecipitated with anti-β-lipoproteins antibodies are observed. This HCV-lipoprotein association has major implications with respect to our understanding of HCV assembly, secretion, and entry. However, cell culture-grown HCV (HCVcc) virions produced in Huh7 cells, which are deficient for very-low-density lipoprotein (VLDL) secretion, are only associated with and dependent on apolipoprotein E (apoE), not apolipoprotein B (apoB), for assembly and infectivity. In contrast to Huh7, HepG2 cells can be stimulated to produce VLDL by both oleic acid treatment and inhibition of the MEK/extracellular signal-regulated kinase (ERK) pathway but are not permissive for persistent HCV replication. Here, we developed a new HCV cell culture model to study the interaction between HCV and lipoproteins, based on engineered HepG2 cells stably replicating a blasticidin-tagged HCV JFH1 strain (JB). Control Huh7.5-JB as well as HepG2-JB cell lines persistently replicated viral RNA and expressed viral proteins with a subcellular colocalization of double-stranded RNA (dsRNA), core, gpE2, and NS5A compatible with virion assembly. The intracellular RNA replication level was increased in HepG2-JB cells upon dimethyl sulfoxide (DMSO) treatment, MEK/ERK inhibition, and NS5A overexpression to a level similar to that observed in Huh7.5-JB cells. Both cell culture systems produced infectious virions, which were surprisingly biophysically and biochemically similar. They floated at similar densities on gradients, contained mainly apoE but not apoB, and were not neutralized by anti-apoB antibodies. This suggests that there is no correlation between the ability of cells to simultaneously replicate HCV as well as secrete VLDL and their capacity to produce LVPs.

Expression of very low density lipoprotein receptor mRNA in circulating human monocytes: its up-regulation by hypoxia.

PubMed

Nakazato, K; Ishibashi, T; Nagata, K; Seino, Y; Wada, Y; Sakamoto, T; Matsuoka, R; Teramoto, T; Sekimata, M; Homma, Y; Maruyama, Y

2001-04-01

Although very low density lipoprotein (VLDL) receptor expression by macrophages has been shown in the vascular wall, it is not clear whether or not circulating monocytes express the VLDL receptor. We investigated the expression of VLDL receptor mRNA in human peripheral blood monocytes and monocyte-derived macrophages by reverse transcriptase polymerase chain reaction (RT-PCR) and nucleotide sequencing after subcloning of PCR product. VLDL receptor mRNA was detected both in peripheral blood monocytes and monocyte-derived macrophages. Expression of VLDL receptor mRNA was upregulated by hypoxia in monocytes, whereas treatment with oxidized LDL, interleukin-1beta or monocyte chemoattractant protein-1 did not affect the levels of VLDL receptor mRNA in monocytes and macrophages. The present study shows a novel response of VLDL receptor mRNA to hypoxia, suggesting a role for VLDL receptor in the metabolism of lipoproteins in the vascular wall and the development of atherosclerosis.

Auto antibodies against oxidized low density lipoprotein in severe preeclampsia.

PubMed

Jain, Meenakshi; Sawhney, Harjeet; Aggarwal, Neelam; Vashistha, Kala; Majumdhar, Siddarth

2004-06-01

To study autoantibody titres against oxidized low density lipoprotein in preeclamsia. Ten millimeters of heparinized blood samples were collected from 20 primigravidae with severe preeclamsia (study group) and 20 gestation-matched normotensive primigravidae (control group). Concentration of malondialdehyde, metabolite of lipid peroxidation were measured in sera by HPLC and autoantibodies against oxidized low density lipoproteins (obtained after oxidation with 2 mm CuSO(4)) were determined by ELISA. Statistical analysis was performed by Student's t-test and chi(2) test. Mean triglyceride levels were significantly (P < 0.001) higher in the study group (193.20 +/- 31.16 mg/dL) compared to the control group (170.60 +/- 23.2 mg/dL). Mean plasma lipid per oxide levels were not significantly different between the study (4.45 +/- 1.28 mmol/mL) and control (3.88 +/- 0.99 mmol/mL) groups. The majority of women in both groups had low antibody titres (<1.32) against low density lipoprotein. Six women (30%) of the study group and four (20%) of the control group had high autoantibody titres (>/=1.32). In preeclamptic women, diastolic blood pressure, the amount of urinary protein excretion and the plasma level of urea were significantly higher (P < 0.05) in patients with higher auto antibody titre. Titres of autoantibodies to oxidized low density lipoprotein were similar in normotensive and preeclamptic women. In preeclamptic women, titres correlated positively with the severity of preeclampsia.

Pharmacologic management of isolated low high-density lipoprotein syndrome.

PubMed

Bermúdez, Valmore; Cano, Raquel; Cano, Clímaco; Bermúdez, Fernando; Arraiz, Nailet; Acosta, Luis; Finol, Freddy; Pabón, María Rebeca; Amell, Anilsa; Reyna, Nadia; Hidalgo, Joaquin; Kendall, Paúl; Manuel, Velasco; Hernández, Rafael

2008-01-01

High-density lipoprotein (HDL) cholesterol is a heterogeneous group of lipoproteins exhibiting a variety of properties like prostacyclin production stimulation, decrease in platelet aggregation, endothelial cell apoptosis inhibition, and low-density lipoprotein oxidation blockade. Epidemiologic studies have shown an inverse relation between HDL cholesterol levels and cardiovascular risk. Low HDL cholesterol is associated with increased risk for myocardial infarction, stroke, sudden death, peripheral artery disease, and postangioplasty restenosis. In contrast, high HDL levels are associated with longevity and protection against atherosclerotic disease development. Given the evolving epidemic of obesity, diabetes mellitus, and metabolic syndrome, the prevalence of low HDL will continue to rise. In the United States, low HDL is present in 35% of men, 15% of women, and approximately 63% of patients with coronary artery disease. Data extracted from the Framingham study highlight that 1-mg increase in HDL levels decreases by 2% to 3% the risk of cardiovascular disease. There is no doubt regarding clinical importance about isolated low HDL, but relatively few clinicians consider a direct therapeutic intervention of this dyslipidemia. In this sense, lifestyle measures should be the first-line strategy to manage low HDL levels. On the other hand, pharmacologic options include niacin, fibrates, and statins. Fibrates appear to reduce risk preferentially in patients with low HDL with metabolic syndrome, whereas statins reduce risk across all levels of HDL. Torcetrapib, a cholesteryl esters transfer protein inhibitor, represented a hope to raise this lipoprotein; however, all clinical trials on this drug had ceased after ILLUMINATE, RADIANCE and ERASE trials had recorded an increase in mortality, rates of myocardial infarction, angina, and heart failure. In the near future, drugs as beta-glucans, Apo-A1 mimetic peptides, and ACAT inhibitors, are the new promises to treat this condition.

Relationship of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to the remainder of the lipid profile: The Very Large Database of Lipids-4 (VLDL-4) study.

PubMed

Quispe, Renato; Manalac, Raoul J; Faridi, Kamil F; Blaha, Michael J; Toth, Peter P; Kulkarni, Krishnaji R; Nasir, Khurram; Virani, Salim S; Banach, Maciej; Blumenthal, Roger S; Martin, Seth S; Jones, Steven R

2015-09-01

High levels of the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio are associated with obesity, metabolic syndrome, and insulin resistance. We evaluated variability in the remaining lipid profile, especially remnant lipoprotein particle cholesterol (RLP-C) and its components (very low-density lipoprotein cholesterol subfraction 3 and intermediate-density lipoprotein cholesterol), with variability in the TG/HDL-C ratio in a very large study cohort representative of the general U.S. We examined data from 1,350,908 US individuals who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL) from 2009 to 2011. Demographic information other than age and sex was not available. Changes to the remaining lipid profile across percentiles of the TG/HDL-C ratio were quantified, as well as by three TG/HDL-C cut-off points previously proposed in the literature: 2.5 (male) and 2 (female), 3.75 (male) and 3 (female), and 3.5 (male and female). The mean age of our study population was 58.7 years, and 48% were men. The median TG/HDL-C ratio was 2.2. Across increasing TG/HDL-C ratios, we found steadily increasing levels of RLP-C, non-HDL-C and LDL density. Among the lipid parameters studied, RLP-C and LDL density had the highest relative increase when comparing individuals with elevated TG/HDL-C levels to those with lower TG/HDL-C levels using established cut-off points. Approximately 47% of TG/HDL-C ratio variance was attributable to RLP-C. In the present analysis, a higher TG/HDL-C ratio was associated with an increasingly atherogenic lipid phenotype, characterized by higher RLP-C along with higher non-HDL-C and LDL density. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The role of high-density lipoprotein cholesterol in risk for posttraumatic stress disorder: taking a nutritional approach toward universal prevention.

PubMed

Hamazaki, K; Nishi, D; Yonemoto, N; Noguchi, H; Kim, Y; Matsuoka, Y

2014-09-01

Several cross-sectional studies, but no prospective studies, have reported an association between an abnormal lipid profile and posttraumatic stress disorder (PTSD). We hypothesized that an abnormal lipid profile might predict risk for developing PTSD. In this prospective study, we analyzed data from 237 antidepressant-naïve severely injured patients who participated in the Tachikawa Cohort of Motor Vehicle Accident Study. High-density lipoprotein cholesterol (HDL-C) levels at baseline were significantly lower in patients with PTSD than those without PTSD at 6 months after motor vehicle accident (MVA) and were inversely associated with risk for PTSD. In contrast, triglycerides (TG) at baseline were significantly higher in patients with PTSD than in those without PTSD at 6 months post-MVA and were positively associated with risk for PTSD. There was no clear association between low-density lipoprotein cholesterol or total cholesterol and risk for PTSD. In conclusion, low HDL-C and high TG may be risk factors for PTSD. Determining lipid profiles might help identify those at risk for PTSD after experiencing trauma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The Predictive Effects of Early Pregnancy Lipid Profiles and Fasting Glucose on the Risk of Gestational Diabetes Mellitus Stratified by Body Mass Index.

PubMed

Wang, Chen; Zhu, Weiwei; Wei, Yumei; Su, Rina; Feng, Hui; Lin, Li; Yang, Huixia

2016-01-01

This study aimed at evaluating the predictive effects of early pregnancy lipid profiles and fasting glucose on the risk of gestational diabetes mellitus (GDM) in patients stratified by prepregnancy body mass index (p-BMI) and to determine the optimal cut-off values of each indicator for different p-BMI ranges. A retrospective system cluster sampling survey was conducted in Beijing during 2013 and a total of 5,265 singleton pregnancies without prepregnancy diabetes were included. The information for each participant was collected individually using questionnaires and medical records. Logistic regression analysis and receiver operator characteristics analysis were used in the analysis. Outcomes showed that potential markers for the prediction of GDM include early pregnancy lipid profiles (cholesterol, triacylglycerols, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratios [LDL-C/HDL-C], and triglyceride to high-density lipoprotein cholesterol ratios [TG/HDL-C]) and fasting glucose, of which fasting glucose level was the most accurate indicator. Furthermore, the predictive effects and cut-off values for these factors varied according to p-BMI. Thus, p-BMI should be a consideration for the risk assessment of pregnant patients for GDM development.

Improvement of physiochemical properties of the tetrahydroazepinoindole series of farnesoid X receptor (FXR) agonists: beneficial modulation of lipids in primates.

PubMed

Lundquist, Joseph T; Harnish, Douglas C; Kim, Callain Y; Mehlmann, John F; Unwalla, Rayomand J; Phipps, Kristin M; Crawley, Matthew L; Commons, Thomas; Green, Daniel M; Xu, Weixin; Hum, Wah-Tung; Eta, Julius E; Feingold, Irene; Patel, Vikram; Evans, Mark J; Lai, Kehdih; Borges-Marcucci, Lisa; Mahaney, Paige E; Wrobel, Jay E

2010-02-25

In an effort to develop orally active farnesoid X receptor (FXR) agonists, a series of tetrahydroazepinoindoles with appended solubilizing amine functionalities were synthesized. The crystal structure of the previously disclosed FXR agonist, 1 (FXR-450), aided in the design of compounds with tethered solubilizing functionalities designed to reach the solvent cavity around the hFXR receptor. These compounds were soluble in 0.5% methylcellulose/2% Tween-80 in water (MC/T) for oral administration. In vitro and in vivo optimization led to the identification of 14dd and 14cc, which in a dose-dependent fashion regulated low density lipoprotein cholesterol (LDLc) in low density lipoprotein receptor knockout (LDLR(-/-)) mice. Compound 14cc was dosed in female rhesus monkeys for 4 weeks at 60 mg/kg daily in MC/T vehicle. After 7 days, triglyceride (TG) levels and very low density lipoprotein cholesterol (VLDLc) levels were significantly decreased and LDLc was decreased 63%. These data are the first to demonstrate the dramatic lowering of serum LDLc levels by a FXR agonist in primates and supports the potential utility of 14cc in treating dyslipidemia in humans beyond just TG lowering.

Distinct Lipoprotein Curves in Normal Weight, Overweight, and Obese Children and Adolescents.

PubMed

Interator, Hagar; Lebenthal, Yael; Hoshen, Moshe; Safra, Inbar; Balicer, Ran; Leshno, Moshe; Shamir, Raanan

2017-12-01

Pediatric lipoprotein curves are based on population-based samples. As obesity, may alter lipoprotein levels, cutoffs not adjusted for body mass index (BMI) are potentially inappropriate. We aimed to develop distinct serum lipid curves based on sex- and BMI-percentiles for children and adolescents. Cross-sectional analysis included all healthy children and adolescents (age range 2-17 years) with available serum lipid concentrations (n = 152,820 of approximately 1.2 million children and adolescents per study year). These children and adolescents were categorized according to sex- and age-stratified BMI-percentiles: 100,375 normal weight (5th-85th percentile), 26,028 overweight (85th-95th percentile) and 26,417 obese (≥95th percentile) individuals. Excluded were individuals with hyperlipidemia, gastrointestinal disease, thyroid disease and lipid-lowering medications. Lambda-Mu-Sigma, smoothed percentile lipid curves were computed. Obese children had a lipid profile pattern throughout childhood and adolescence similar to that of normal weight subjects but with a significant upward shift in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TGs) and a downward shift in high-density lipoprotein-cholesterol (HDL-C). Obese boys had 13 mg/dL higher TC levels (P < 0.001), 11 mg/dL higher LDL-C levels, 15 mg/dL higher non-HDL-C levels, and 5 mg/dL lower HDL-C levels (P < 0.001). Obese girls had 6 mg/dL higher TC levels, 7 mg/dL higher LDL-C levels, 11 mg/dl higher non-HDL-C levels, and 6 mg/dL lower HDL-C levels (P < 0.001). Across a large, nationally representative cohort of children and adolescents, lipoprotein levels were found to vary in relation to weight status. On the basis of these findings, it is suggested that when evaluating the lipid profile in the pediatric population, in addition to sex-based curves, clinical decision making may require consideration of BMI-stratified curves.

Comparing fluorescence-based cell-free assays for the assessment of antioxidative capacity of high-density lipoproteins

USDA-ARS?s Scientific Manuscript database

Background: Population studies have shown an inverse association between high-density lipoprotein (HDL) cholesterol levels and risk of coronary heart disease (CHD). HDL has different functions, including the ability to protect biological molecules from oxidation. Our aim was to evaluate the performa...

Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphism...

Glucose, lipid, and lipoprotein levels in sheep naturally infected with Fasciola hepatica.

PubMed

Kozat, Süleyman; Denizhan, Vural

2010-06-01

This study was designed to investigate serum glucose, lipid, and lipoprotein in sheep naturally infected with Fasciola hepatica. Ten healthy sheep and 15 infected with F. hepatica were used in study. Serum concentrations of total protein (TP), albumin, glucose, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoproteins (VLDL), and serum activities of AST, ALT, GGT, and LDH were measured using a Roche-Cobas Integra 800 auto-analyzer. At day 0 (prior to treatment) and on the 28th day (after treatment) the serum concentrations of TP, albumin, glucose, cholesterol, triglyceride, HDL, LDL, and VLDL values in sheep with F. hepatica were significantly lower than those of the control group, while serum activities of AST, ALT, GGT, and LDH of lambs with F. hepatica were significantly higher than those of the control group. At day 56 (after treatment), none of the variables was significantly different between control sheep and those that received treatment for fascioliasis (P > 0.05). Nutritional management may be used to reduce the impact of fascioliasis.

Genetics of Lipid and Lipoprotein Disorders and Traits.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2016-01-01

Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components. Recent advances in genetics of plasma lipids and lipoproteins include the following: (1) expanding the range of genes causing monogenic dyslipidemias, particularly elevated LDL cholesterol; (2) appreciating the role of polygenic effects in such traits as familial hypercholesterolemia and combined hyperlipidemia; (3) accumulating a list of common variants that determine plasma lipids and lipoproteins; (4) applying exome sequencing to identify collections of rare variants determining plasma lipids and lipoproteins that via Mendelian randomization have also implicated gene products such as NPC1L1 , APOC3 , LDLR , APOA5 , and ANGPTL4 as causal for atherosclerotic cardiovascular disease; and (5) using naturally occurring genetic variation to identify new drug targets, including inhibitors of apolipoprotein (apo) C-III, apo(a), ANGPTL3, and ANGPTL4. Here, we compile this disparate range of data linking human genetic variation to plasma lipids and lipoproteins, providing a "one stop shop" for the interested reader.

Mechanisms of Dyslipoproteinemias in Systemic Lupus Erythematosus

PubMed Central

Borba, Eduardo F.; Carvalho, Jozelio F.; Bonfá, Eloísa

2006-01-01

Autoimmunity and inflammation are associated with marked changes in lipid and lipoprotein metabolism in SLE. Autoantibodies and cytokines are able to modulate lipoprotein lipase (LPL) activity, a key enzyme in lipid metabolism, with a consequent “lupus pattern” of dyslipoproteinemia characterized by elevated levels of very low-density lipoprotein cholesterol (VLDL) and triglycerides (TG) and lower high-density lipoprotein cholesterol (HDL) levels. This pattern favors an enhanced LDL oxidation with a subsequent deleterious foam cell formation. Autoantibodies and immunocomplexes may aggravate this oxidative injury by inducing accumulation and deposition of oxLDL in endothelial cells. Drugs and associated diseases usually magnify the close interaction of these factors and further promote the proatherogenic environment of this disease. PMID:17162363

Comparison of human plasma low- and high-density lipoproteins as substrates for lecithin: cholesterol acyltransferase.

PubMed

Barter, P J; Hopkins, G J; Gorjatschko, L

1984-01-17

A recent observation that lecithin: cholesterol acyltransferase (EC 2.3.1.43) interacts with both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in human plasma is in apparent conflict with an earlier finding that the purified enzyme, while highly reactive with isolated HDL, was only minimally reactive with LDL. There is evidence, however, that lecithin: cholesterol acyltransferase may exist physiologically as a component of a complex with other proteins and that studies with the isolated enzyme may therefore provide misleading results. Consequently, interactions of the enzyme with isolated human lipoproteins have been re-examined in incubations containing lecithin: cholesterol acyltransferase as a component of human lipoprotein-free plasma in which a physiologically active complex of the enzyme with other proteins may have been preserved. In this system there was a ready esterification of the free cholesterol associated with both LDL and HDL-subfraction 3 (HDL3) in reactions that obeyed typical enzyme-saturation kinetics. For a given preparation of lipoprotein-free plasma the Vmax values with LDL and with HDL3 were virtually identical. The apparent Km for free cholesterol associated with HDL3 was 5.6 X 10(-5) M, while for that associated with LDL it was 4.1 X 10(-4) M. This implied that, in terms of free cholesterol concentration, the affinity of HDL3 for lecithin: cholesterol acyltransferase was about 7-times greater than that of LDL. When expressed in terms of lipoprotein particle concentration, however, it was apparent that the affinity of LDL for the enzyme was considerably greater than that of HDL3. When the lipoprotein fractions were equated in terms of lipoprotein surface area, the apparent affinities of the two fractions for the enzyme were found to be comparable.

Short-term cooling increases serum triglycerides and small high-density lipoprotein levels in humans.

PubMed

Hoeke, Geerte; Nahon, Kimberly J; Bakker, Leontine E H; Norkauer, Sabine S C; Dinnes, Donna L M; Kockx, Maaike; Lichtenstein, Laeticia; Drettwan, Diana; Reifel-Miller, Anne; Coskun, Tamer; Pagel, Philipp; Romijn, Fred P H T M; Cobbaert, Christa M; Jazet, Ingrid M; Martinez, Laurent O; Kritharides, Leonard; Berbée, Jimmy F P; Boon, Mariëtte R; Rensen, Patrick C N

Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase-mediated catabolism of triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men. Body mass index-matched young, lean men were exposed to a personalized cooling protocol for 2 hours. Before and after cooling, serum samples were collected for analysis of lipids and lipoprotein composition by 1 H-nuclear magnetic resonance. Adenosine triphosphate-binding cassette A1 (ABCA1)-mediated cholesterol efflux capacity of HDL was measured using [ 3 H]cholesterol-loaded ABCA1-transfected Chinese hamster ovary cells. Short-term cooling increased serum levels of free fatty acids, triglycerides, and cholesterol. Cooling increased the concentration of large very low-density lipoprotein (VLDL) particles accompanied by increased mean size of VLDL particles. In addition, cooling enhanced the concentration of small LDL and small HDL particles as well as the cholesterol levels within these particles. The increase in small HDL was accompanied by increased ABCA1-dependent cholesterol efflux in vitro. Our data show that short-term cooling increases the concentration of large VLDL particles and increases the generation of small LDL and HDL particles. We interpret that cooling increases VLDL production and turnover, which results in formation of surface remnants that form small HDL particles that attract cellular cholesterol. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The association between lipid parameters and obesity in university students.

PubMed

Hertelyova, Z; Salaj, R; Chmelarova, A; Dombrovsky, P; Dvorakova, M C; Kruzliak, P

2016-07-01

Abdominal obesity is associated with high plasma triglyceride and with low plasma high-density lipoprotein cholesterol levels. Objective of the study was to find an association between plasma lipid and lipoprotein levels and anthropometric parameters in abdominal obesity in Slovakian university students. Lipid profile and anthropometric parameters of obesity were studied in a sample of 419 probands, including 137 men and 282 women. Males had higher values of non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) than females, but these differences were not significant. Females had significantly (P < 0.05) higher TC and HDL-C (P < 0.001) than males. In comparison, all anthropometric parameters in the males were significantly (P < 0.001) higher than in the females. A positive correlation between non-HDL-C, TG, VLDL-C and anthropometric parameters (BMI, WC, WHR, WHtR) was found at P < 0.001. LDL was positively correlated with BMI, WCF, WHtR and TC with BMI, WHtR at P < 0.001. We also observed a correlation between TC-WCF and LDL-WHR at P < 0.01. A negative correlation was found between HDL and all monitored anthropometric parameters at P < 0.001. On the other hand, no correlation between TC and WHR was detected. This study shows an association between plasma lipid and lipoprotein levels and anthropometric parameters in abdominal obesity in young people, predominantly university students.

Biomimetics: reconstitution of low-density lipoprotein for targeted drug delivery and related theranostic applications.

PubMed

Zhu, Chunlei; Xia, Younan

2017-12-11

Low-density lipoprotein (LDL), one of the four major groups of lipoproteins for lipid transport in vivo, is emerging as an attractive carrier for the targeted delivery of theranostic agents. In contrast to the synthetic systems, LDL particles are intrinsically biocompatible and biodegradable, together with reduced immunogenicity and natural capabilities to target cancerous cells and to escape from the recognition and elimination by the reticuloendothelial system. Enticed by these attributes, a number of strategies have been developed for reconstituting LDL particles, including conjugation to the apolipoprotein, insertion into the phospholipid layer, and loading into the core. Here we present a tutorial review on the development of reconstituted LDL (rLDL) particles for theranostic applications. We start with a brief introduction to LDL and LDL receptor, as well as the advantages of using rLDL particles as a natural and versatile platform for the targeted delivery of theranostic agents. After a discussion of commonly used strategies for the reconstitution of LDL, we highlight the applications of rLDL particles in the staging of disease progression, treatment of lesioned tissues, and delivery of photosensitizers for photodynamic cancer therapy. We finish this review with a perspective on the remaining challenges and future directions.

Polyphenols isolated from virgin coconut oil attenuate cadmium-induced dyslipidemia and oxidative stress due to their antioxidant properties and potential benefits on cardiovascular risk ratios in rats

PubMed Central

Famurewa, Ademola Clement; Ejezie, Fidelis Ebele

2018-01-01

Objective: Literature has confirmed the pathogenic role of cadmium (Cd) and its exposure in the induction of dyslipidemia implicated in the development and increasing incidence of cardiovascular diseases. The current study explored whether polyphenolics isolated from virgin coconut oil (VCO) prevent Cd-induced dyslipidemia and investigate the underlying mechanism of action, in rats. Materials and Methods: Rats were pretreated with VCO polyphenols (10, 20 and 50 mg/kg body weight; orally) 2 weeks prior to concurrent Cd administration (5 mg/kg) for 5 weeks. Subsequently, serum concentrations of lipid and lipoprotein cholesterol and cardiovascular risk ratios were determined. Hepatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as reduced glutathione (GSH) and malondialdehyde (MDA) contents were analyzed. Results: Sub-chronic Cd administration significantly increased the serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol while markedly reduced high density lipoprotein cholesterol. Hepatic activities of SOD and CAT as well as GSH content were suppressed by Cd, whereas MDA level was obviously increased. The co-administration of VCO polyphenol with Cd remarkably restored lipid profile and cardiovascular risk ratios and stabilized antioxidant defense systems comparable to control group. Conclusion: This is the first study presenting that polyphenols isolated from VCO prevent Cd-induced lipid abnormalities and cardiovascular risk ratios by improving antioxidant defense systems. PMID:29387575

Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography

PubMed Central

2013-01-01

Background Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. Methods Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). Results Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). Conclusions HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin. PMID:24161017

The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart.

PubMed

Korolenko, Tatyana A; Tuzikov, Fedor V; Johnston, Thomas P; Tuzikova, Natalia A; Kisarova, Yana A; Zhanaeva, Svetlana Ya; Alexeenko, Tatyana V; Zhukova, Natalia A; Brak, Ivan V; Spiridonov, Victor K; Filjushina, Elena E; Cherkanova, Marina S; Monoszon, Anna A

2012-11-01

The effects of repeated administration of poloxamer 407 (P-407) on lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions, as well as the effect on liver and heart proteases, were studied. Repeated administration of P-407 to male CBA mice resulted in a model of atherosclerosis with increased diastolic blood pressure; there was a drastic increase in total serum cholesterol and especially TG. A novel small-angle X-ray scattering method for the determination of the fractional and subfractional composition of LP-C and LP-TG was used. In chronically P-407-treated mice, P-407 significantly increased atherogenic low-density lipoprotein C (LDL-C) fractions, as well as intermediate-density lipoprotein C (IDL-C), and LDL₁₋₃-C subfractions, and very-low-density lipoprotein-C (VLDL-C) fractions, as well as VLDL₁₋₂-C and VLDL₃₋₅-C subfractions), to a lesser extent, the total anti-atherogenic high-density lipoprotein C (HDL-C) fraction, as well as HDL₂-C and HDL₃-C subfractions. Additionally, we demonstrated an increase in the serum chitotriosidase activity, without significant changes in serum matrix metalloprotease (MMP) activity. Morphological changes observed in P-407-treated mice included atherosclerosis in the heart and storage syndrome in the liver macrophages. P-407 significantly increased the activity of cysteine, aspartate proteases, and MMPs in the heart, and only the activity of cathepsin B and MMPs in the liver of mice. Thus, repeated administration of P-407 to mice induced atherosclerosis secondary to sustained dyslipidemia and formation of foamy macrophages in liver, and also modulated the activity of heart and liver proteases.

Air pollution is associated with the development of atherosclerosis via the cooperation of CD36 and NLRP3 inflammasome in ApoE-/- mice.

PubMed

Du, Xihao; Jiang, Shuo; Zeng, Xuejiao; Zhang, Jia; Pan, Kun; Zhou, Ji; Xie, Yuquan; Kan, Haidong; Song, Weimin; Sun, Qinghua; Zhao, Jinzhuo

2018-06-15

Previous studies have indicated that the main air pollutant fine particulate matter (≤2.5 μm; PM 2.5 ) exposure is associated with the development of atherosclerosis. Although the mechanism is not fully illustrated, the inflammatory responses play an important role. The present study aimed to explore whether PM 2.5 -exacerbated atherosclerosis was mediated by the cooperation of cluster of differentiation 36 (CD36) and nucleotide-binding oligomerization domain-like receptor protein (NLRP3) inflammasome in apolipoprotein E -/- (ApoE -/- ) mice. Thirty-two ApoE -/- mice were randomly divided into two groups. One group was fed with high fat chow (HFC) for 10 weeks to establish atherosclerotic model, and the other was fed with normal chow (NC). From week 11, the mice were exposed to concentrated PM 2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM 2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic root than that in the FA mice. Compared with the FA mice, PM mice appeared a decrease in high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 along with an increase in apolipoprotein B, low density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (ox-LDL). Moreover, PM 2.5 exposure induced increase of CD36 in serum and aorta. In both NC and HFC groups, NLRP3 inflammasome activation-related indicators were activated or increased in the aorta of the PM mice when compared with the FA mice. The cooperation of CD36 and NLRP3 inflammasome activation may be the potential mechanisms linkixposed to concentrated PM 2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM 2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic root than that in the FA mice. Compared with the FA mice, PM mice appeared a decrease in high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 along with an increase in apolipoprotein B, low density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (ox-LDL). Moreover, PM 2.5 exposure induced increase of CD36 in serum and aorta. In both NC and HFC groups, NLRP3 inflammasome activation-related indicators were activated or increased in the aorta of the PM mice when compared with the FA mice. The cooperation of CD36 and NLRP3 inflammasome activation may be the potential mechanisms linking air pollution and HFC-induced atherosclerosis even in the mice with NC intake. Copyright © 2018. Published by Elsevier B.V.

The influence of a high level of corn oil on rat serum lipoproteins.

PubMed

Narayan, K A; McMullen, J J; Butler, D P; Wakefield, T; Calhoun, W K

1976-01-01

Although the stated requirement for linoleic acid in humans is less than 2% of the dietary calories, recently there has been considerable emphasis on the necessity to substitute dietary polyunsaturates for saturates in order to reduce serum cholesterol levels. In this study we have sought to determine the nutritional consequences of feeding a very high level of linoleate to rats. Three groups of thirty adult animals each were fed a semipurified diet consisting by weight of casein 17%; mineral mixture 5.5%; vitamin mixture in glucose 2.2%; cellulose fiber 3.0%; and corn oil 0% (group A), 10% (group B) or 40% (group C), which was provided at the expense of glucose. At the end of four weeks on the diets, blood was obtained in the fasting state from 16 rats in each group. The serum was ultracentrifugally fractionated into six classes of lipoproteins and analyzed for lipid composition and protein content. Disc gel electrophoresis using lipid and protein stains established that the various lipoprotein subclasses were reasonably free of adjacent density fractions. Although the total serum cholesterol levels were practically the same in the three groups, the cholesterol moiety of the major low density lipoproteins, LDL2 (d 1.019-1.050), but not of very low density lipoproteins, VLDL (d 1.006) or low density lipoproteins, LDL1 (d 1.006-1.019), was substantially and very significantly increased in rats fed the high level of corn oil as compared to the other groups. The concentration of the very low density lipoproteins was significantly lower in group C than in the groups A and B. The LDL2 concentration but not that of LDL1 was significantly greater in group C as compared to group A. The cholesterol/total lipid ratio was significantly greater in both LDL2 and LDL1 but not in VLDL of group C as compared with group A. The serum high density lipoproteins were relatively less influenced by the ingestion of an excessive level of corn oil at this time period. The serum lipoprotein levels as well as their lipid composition were generally similar in groups A and B and suggested that a moderate level (5%) of dietary linoleate did not cause any untoward changes in rats. On the basis of current information on the metabolism of lipoproteins, it has been proposed that the increase in rat serum LDL2 of group C reflects the status of the liver and that a large portion of the cholesterol moiety of LDL2 is perhaps derived from the liver while the protein and phospholipid portions may represent remnants of VLDL catabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Sedentary lifestyle and its relation to cardiovascular risk factors, insulin resistance and inflammatory profile.

PubMed

León-Latre, Montserrat; Moreno-Franco, Belén; Andrés-Esteban, Eva M; Ledesma, Marta; Laclaustra, Martín; Alcalde, Víctor; Peñalvo, José L; Ordovás, José M; Casasnovas, José A

2014-06-01

To analyze the association between sitting time and biomarkers of insulin resistance and inflammation in a sample of healthy male workers. Cross-sectional study carried out in a sample of 929 volunteers belonging to the Aragon Workers' Health Study cohort. Sociodemographic, anthropometric, pharmacological and laboratory data were collected: lipids-total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B-100, lipoprotein (a)-, insulin resistance-glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, insulin, and triglyceride/high-density lipoprotein cholesterol ratio-, and inflammatory profile-C-reactive protein and leukocytes. Information on sitting time and physical activity was assessed using a questionnaire. Sedentary behavior was analyzed in terms of prevalences and medians, according to tertiles, using a multivariate model (crude and adjusted linear regression) with biomarkers of inflammation and insulin resistance. The most sedentary individuals had higher body mass index, greater waist circumference, and higher systolic blood pressure, with a significant upward trend in each tertile. Likewise, they had a worse lipid profile with a higher C-reactive protein level, homeostasis model assessment of insulin resistance index, triglyceride/high-density lipoprotein cholesterol ratio, and insulin concentration. In the multivariate analysis, we observed a significant association between the latter parameters and sitting time in hours (log C-reactive protein [β = 0.07], log homeostasis model assessment of insulin resistance index [β = 0.05], triglyceride/high-density lipoprotein cholesterol ratio [β = 0.23], and insulin [β = 0.44]), which remained after adjustment for metabolic equivalents-h/week. Workers who spend more time sitting show a worse inflammatory and insulin resistance profile independently of the physical activity performed. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic agent in an animal model, and a significant contributor to antioxidants in the European and American Diets.

PubMed

Vinson, Joe A; Proch, John; Bose, Pratima; Muchler, Sean; Taffera, Pamela; Shuta, Donna; Samman, Najwa; Agbor, Gabriel A

2006-10-18

Chocolate today is often viewed as a food or snack with little nutritional value. The high saturated fat content of chocolate has also contributed to the belief that its consumption increases the risk of heart disease. However, recent human studies have proven that chocolate has beneficial effects on some pathogenic mechanisms of heart disease such as endothelial function and blood pressure. Although the antioxidant properties of chocolate have been known for some time, there has been no examination of its place in the U.S. diet as a source of antioxidants. This paper demonstrates that chocolate makes a significant contribution to U.S. per capita dietary antioxidants and by inference the European Community's. In the U.S. diet chocolate is the third highest daily per capita antioxidant source. An ex vivo study shows that epicatechin, a major polyphenol in chocolate and chocolate extracts, is a powerful inhibitor of plasma lipid oxidation due to polyphenols' ability to bind to lower density lipoproteins. Conversely, the fat from chocolate alone is a pro-oxidant in this model. This is also demonstrated in an in vivo human study. After consumption of dark chocolate and cocoa powder, the lower density lipoproteins isolated from plasma were protected from oxidation compared to the lipoproteins isolated after cocoa butter consumption, which were put under oxidative stress. In an animal model of atherosclerosis, cocoa powder at a human dose equivalent of two dark chocolate bars per day significantly inhibited atherosclerosis, lowered cholesterol, low-density lipoprotein, and triglycerides, raised high-density lipoprotein, and protected the lower density lipoproteins from oxidation. Chocolate has thus been shown to have potential beneficial effects with respect to heart disease.

Predictive value of body mass index to metabolic syndrome risk factors in Syrian adolescents.

PubMed

Al-Bachir, Mahfouz; Bakir, Mohamad Adel

2017-06-25

Obesity has become a serious epidemic health problem in both developing and developed countries. There is much evidence that obesity among adolescents contributed significantly to the development of type 2 diabetes and coronary heart disease in adulthood. Very limited information exists on the prevalence of overweight, obesity, and associated metabolic risk factors among Syrian adolescents. Therefore, the purpose of this study was to determine the relationship between obesity determined by body mass index and the major metabolic risk factors among Syrian adolescents. A cross-sectional study of a randomly selected sample of 2064 apparently healthy Syrian adolescents aged 18 to 19 years from Damascus city, in Syria, was performed. Body mass index and blood pressure were measured. Serum concentrations of glucose, triglycerides, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol were determined. Metabolic syndrome was defined using the national criteria for each determined metabolic risk factor. Individuals with a body mass index 25 to 29.9 were classified as overweight, whereas individuals with a body mass index ≥30 were classified as obese. A receiver operating characteristics curve was drawn to determine appropriate cut-off points of the body mass index for defining overweight and obesity, and to indicate the performance of body mass index as a predictor of risk factors. The obtained data showed that blood pressure and the overall mean concentrations of fasting blood sugar, triglycerides, cholesterol, low-density lipoprotein-cholesterol, and triglycerides/high-density lipoprotein-cholesterol were significantly higher in overweight and obese adolescent groups (p <0.0001) in comparison with the normal group. Based on receiver operating characteristics calculation for body mass index and some metabolic risks, the data suggest the best body mass index cut-offs ranged between 23.25 and 24.35 kg/m 2 . A strong association between overweight and obesity as determined by body mass index and high concentrations of metabolic syndrome components has been demonstrated. Although body mass index values were lower than the international cut-offs, these values were good predictors of some metabolic abnormalities in Syrian adolescents; body mass index is a good predictor of these abnormalities in this population.

Excessive centrifugal fields damage high density lipoprotein[S

PubMed Central

Munroe, William H.; Phillips, Martin L.; Schumaker, Verne N.

2015-01-01

HDL is typically isolated ultracentrifugally at 40,000 rpm or greater, however, such high centrifugal forces are responsible for altering the recovered HDL particle. We demonstrate that this damage to HDL begins at approximately 30,000 rpm and the magnitude of loss increases in a rotor speed-dependent manner. The HDL is affected by elevated ultracentrifugal fields resulting in a lower particle density due to the shedding of associated proteins. To circumvent the alteration of the recovered HDL, we utilize a KBr-containing density gradient and a lowered rotor speed of 15,000 rpm to separate the lipoproteins using a single 96 h centrifugation step. This recovers the HDL at two density ranges; the bulk of the material has a density of about 1.115 g/ml, while lessor amounts of material are recovered at >1.2 g/ml. Thus, demonstrating the isolation of intact HDL is possible utilizing lower centrifuge rotor speeds. PMID:25910941

Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

PubMed

Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

2017-08-01

Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

PubMed

Westerterp, Marit; Murphy, Andrew J; Wang, Mi; Pagler, Tamara A; Vengrenyuk, Yuliya; Kappus, Mojdeh S; Gorman, Darren J; Nagareddy, Prabhakara R; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S; Welch, Carrie; Fisher, Edward A; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R

2013-05-24

Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

Dyslipidemias and Cardiovascular Prevention: Tailoring Treatment According to Lipid Phenotype.

PubMed

Sanin, Veronika; Pfetsch, Vanessa; Koenig, Wolfgang

2017-07-01

This study aimed to present the current information on the genetic background of dyslipidemias and provide insights into the complex pathophysiological role of several plasma lipids/lipoproteins in the pathogenesis of atherosclerotic cardiovascular disease. Furthermore, we aim to summarize established therapies and describe the scientific rationale for the development of novel therapeutic strategies. Evidence from genetic studies suggests that besides lowering low-density lipoprotein cholesterol, pharmacological reduction of triglyceride-rich lipoproteins, or lipoprotein(a) will reduce risk for coronary heart disease. Dyslipidemia, in particular hypercholesterolemia, is a common clinical condition and represents an important determinant of atherosclerotic vascular disease. Treatment decisions are currently guided by the causative lipid phenotype and the presence of other risk factors suggesting a very high cardiovascular risk. Therefore, the identification of lipid disorders and the optimal combination of therapeutic strategies provide an outstanding opportunity for reducing the onset and burden of cardiovascular disease.

Effects of intensive atorvastatin and rosuvastatin treatment on apolipoprotein B-48 and remnant lipoprotein cholesterol levels

USDA-ARS?s Scientific Manuscript database

Atorvastatin and rosuvastatin at maximal doses are both highly effective in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. Rosuvastatin has been shown to be more effective than atorvastatin in lowering LDL-C, small dense LDL-C and in raising high-density lipoprote...

Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

USDA-ARS?s Scientific Manuscript database

Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men.

PubMed

Riales, R; Albrink, M J

1981-12-01

Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

Association of ADRB2 polymorphism with triglyceride levels in Tongans.

PubMed

Naka, Izumi; Ohashi, Jun; Kimura, Ryosuke; Inaoka, Tsukasa; Matsumura, Yasuhiro

2013-07-23

Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index.

Apolipoprotein B variant derived from rat intestine.

PubMed Central

Krishnaiah, K V; Walker, L F; Borensztajn, J; Schonfeld, G; Getz, G S

1980-01-01

A variant of apolipoprotein B has been observed in the lymph lipoproteins [chylomicrons, very low density lipoproteins (VLDL), and low density lipoproteins (LDL)] of rats, in the plasma VLDL of fed rats, and in the plasma VLDL and LDL of rats fed a high-fat, high-cholesterol diet. It is the sole apolipoprotein B in the chylomicrons and VLDL of lymph. It differs from the apolipoprotein B of normal plasma LDL in its immunological properties and in its apparent molecular weight from electrophoresis on 3.5% NaDodSO4/polyacrylamide gel. Images PMID:6933436

Resistance training is medicine: effects of strength training on health.

PubMed

Westcott, Wayne L

2012-01-01

Inactive adults experience a 3% to 8% loss of muscle mass per decade, accompanied by resting metabolic rate reduction and fat accumulation. Ten weeks of resistance training may increase lean weight by 1.4 kg, increase resting metabolic rate by 7%, and reduce fat weight by 1.8 kg. Benefits of resistance training include improved physical performance, movement control, walking speed, functional independence, cognitive abilities, and self-esteem. Resistance training may assist prevention and management of type 2 diabetes by decreasing visceral fat, reducing HbA1c, increasing the density of glucose transporter type 4, and improving insulin sensitivity. Resistance training may enhance cardiovascular health, by reducing resting blood pressure, decreasing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. Resistance training may promote bone development, with studies showing 1% to 3% increase in bone mineral density. Resistance training may be effective for reducing low back pain and easing discomfort associated with arthritis and fibromyalgia and has been shown to reverse specific aging factors in skeletal muscle.

Diet and the role of lipoproteins, lipases, and thyroid hormones in coronary lesion growth

NASA Technical Reports Server (NTRS)

Barth, Jacques D.; Jansen, Hans; Reiber, Johan H. C.; Birkenhager, Jan C.; Kromhout, Daan

1987-01-01

The relationships between the coronary lesion growth and the blood contents of lipoprotein fractions, thyroic hormones, and the lipoprotein lipase activity were investigated in male patients with severe coronary atherosclerosis, who participated in a lipid-lowering dietary intervention program. A quantitative computer-assisted image-processing technique was used to assess the severity of coronary obstructions at the beginning of the program and at its termination two years later. Based on absolute coronary scores, patients were divided into a no-lesion growth group (14 patients) and a progression group (21 paients). At the end of the trial, the very-low-density lipoprotein cholesterol and triglycerides were found to be significantly higher, while the high-density lipoprotein cholesterol and hepatic lipase (HL) were lower in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions.

The effects of exercise on the lipoprotein subclass profile: a meta-analysis of 10 interventions

PubMed Central

Sarzynski, Mark A.; Burton, Jeffrey; Rankinen, Tuomo; Blair, Steven N.; Church, Timothy S.; Després, Jean-Pierre; Hagberg, James M.; Landers-Ramos, Rian; Leon, Arthur S.; Mikus, Catherine R.; Rao, D.C.; Seip, Richard L.; Skinner, James S.; Slentz, Cris A.; Thompson, Paul D.; Wilund, Kenneth R.; Kraus, William E.; Bouchard, Claude

2015-01-01

Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1,555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N=106), DREW (N=385), GERS (N=79), HERITAGE (N=715), STRRIDE I (N=168) and II (N=102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk. PMID:26520888

The monocyte counts to HDL cholesterol ratio in obese and lean patients with polycystic ovary syndrome.

PubMed

Usta, Akin; Avci, Eyup; Bulbul, Cagla Bahar; Kadi, Hasan; Adali, Ertan

2018-04-10

Women with polycystic ovary syndrome are more likely to suffer from obesity, insulin resistance, and chronic low-grade inflammation. In fact, the excessive activation of monocytes exacerbates oxidative stress and inflammation. However, high-density lipoprotein cholesterol neutralizes the pro-inflammatory and pro-oxidant effects of monocytes. The aim of this study is to investigate whether monocyte counts to high-density lipoprotein cholesterol ratio can predict the inflammatory condition in patients with polycystic ovary syndrome. In this cross-sectional study, a total of 124 women (61 of them with polycystic ovary syndrome and 63 age-matched healthy volunteers) were included in the study population. Obese polycystic ovary syndrome patients (n = 30) with a body mass index of ≥25 kg/m 2 and lean polycystic ovary syndrome patients (n = 31) with a body mass index of < 25 kg/m 2 were compared to age-and body mass index-matched healthy subjects (30 obese and 33 non-obese). The monocyte counts to high density lipoprotein cholesterol values in women with polycystic ovary syndrome were significantly higher than in control subjects (p = 0.0018). Moreover, a regression analysis revealed that body mass index, the homeostasis model assessment of insulin resistance and the high sensitivity C-reactive protein levels were confounding factors that affected the monocyte counts to high density lipoprotein cholesterol values. Additionally, a univariate and multivariate logistic regression analysis demonstrated that the increased monocyte counts to high density lipoprotein cholesterol values were more sensitive than the other known risk factors (such as increased body mass index, homeostasis model assessment of insulin resistance and high sensitive C-reactive protein levels) in the prediction of the inflammation in patients with polycystic ovary syndrome. The present study demonstrated that the monocyte count to high density lipoprotein cholesterol may be a novel and useful predictor of the presence of polycystic ovary syndrome.

[THE SPIRIT CHOLESTEROL, BIOLOGICA L ROLE AT STAGES OF PHYLOGENESIS, MECHANISMS OF INHIBITION OF SYNTHESIS OF STEROL BY STATINS, FACTORS OF PHARMACOGENOMICS AND DIAGNOSTIC SIGNIFICANCE OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

PubMed

Titov, V N; Kotlovskii, M Yu; Pokrovskii, A A; Kotlovskaia, O S; Osedko, A V; Titova, N M; Kotlovskii, Yu V; Digaii, A M

2015-04-01

The hypolipidemic effect of statins is realized by inhibition of synthesis of local pool of cholesterol spirit in endoplasmic net of hepatocytes. The cholesterol spirit covers all hydrophobic medium of triglycerides with polar mono layer of phosphatidylcholines and cholesterol spirit prior to secretion of lipoproteins of very low density into hydrophilic medium. The lesser mono layer between lipase enzyme and triglycerides substrate contains of cholesterol spirit the higher are the parameters of hydrolysis of palmitic and oleic lipoproteins of very low density. The sequence of effect of statins is as follows: blocking of synthesis in hepatocytes and decreasing of content of unesterified cholesterol spirit in blood plasma; activation of hydrolysis of triglycerides in palmitic and oleic lipoproteins of very low density; formation of ligand lipoproteins of very low density and their absorption by cells by force of apoB-100 endocytosis; decreasing in blood of content of polyenoic fatty acids, equimolar esterified by cholesterol spirit, polyethers of cholesterol spirit and decreasing of level of cholesterol spirit-lipoproteins of very low density. There is no way to eliminate aphysiological effect of disordered biological function of trophology (nutrition) on metabolism of fatty acids in population by means of pharmaceuticals intake. It is necessary to eliminate aphysiological effect of environment. To decrease rate of diseases of cardiovascular system one has to decrease in food content of saturated fatty acids and in the first instance palmitic saturated fatty acid, trans-form fatty acid, palmitoleic fatty acids up to physiological values and increase to the same degree the content of polyenoic fatty acids. The saturated fatty acids block absorption of polyenoic fatty acids by cells. The atherosclerosis is a deficiency of polyenoic fatty acids under surplus of palmitic saturated fatty acid.

Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

PubMed

Baker, Jason V; Sharma, Shweta; Achhra, Amit C; Bernardino, Jose Ignacio; Bogner, Johannes R; Duprez, Daniel; Emery, Sean; Gazzard, Brian; Gordin, Jonathan; Grandits, Greg; Phillips, Andrew N; Schwarze, Siegfried; Soliman, Elsayed Z; Spector, Stephen A; Tambussi, Giuseppe; Lundgren, Jens

2017-05-22

HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4 + cell counts >500 cells/mm 3 . Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm 3 , an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant." URL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Biological, clinical and population relevance of 95 loci for blood lipids.

PubMed

Teslovich, Tanya M; Musunuru, Kiran; Smith, Albert V; Edmondson, Andrew C; Stylianou, Ioannis M; Koseki, Masahiro; Pirruccello, James P; Ripatti, Samuli; Chasman, Daniel I; Willer, Cristen J; Johansen, Christopher T; Fouchier, Sigrid W; Isaacs, Aaron; Peloso, Gina M; Barbalic, Maja; Ricketts, Sally L; Bis, Joshua C; Aulchenko, Yurii S; Thorleifsson, Gudmar; Feitosa, Mary F; Chambers, John; Orho-Melander, Marju; Melander, Olle; Johnson, Toby; Li, Xiaohui; Guo, Xiuqing; Li, Mingyao; Shin Cho, Yoon; Jin Go, Min; Jin Kim, Young; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Twee-Hee Ong, Rick; Croteau-Chonka, Damien C; Lange, Leslie A; Smith, Joshua D; Song, Kijoung; Hua Zhao, Jing; Yuan, Xin; Luan, Jian'an; Lamina, Claudia; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y L; Wright, Alan F; Witteman, Jacqueline C M; Wilson, James F; Willemsen, Gonneke; Wichmann, H-Erich; Whitfield, John B; Waterworth, Dawn M; Wareham, Nicholas J; Waeber, Gérard; Vollenweider, Peter; Voight, Benjamin F; Vitart, Veronique; Uitterlinden, Andre G; Uda, Manuela; Tuomilehto, Jaakko; Thompson, John R; Tanaka, Toshiko; Surakka, Ida; Stringham, Heather M; Spector, Tim D; Soranzo, Nicole; Smit, Johannes H; Sinisalo, Juha; Silander, Kaisa; Sijbrands, Eric J G; Scuteri, Angelo; Scott, James; Schlessinger, David; Sanna, Serena; Salomaa, Veikko; Saharinen, Juha; Sabatti, Chiara; Ruokonen, Aimo; Rudan, Igor; Rose, Lynda M; Roberts, Robert; Rieder, Mark; Psaty, Bruce M; Pramstaller, Peter P; Pichler, Irene; Perola, Markus; Penninx, Brenda W J H; Pedersen, Nancy L; Pattaro, Cristian; Parker, Alex N; Pare, Guillaume; Oostra, Ben A; O'Donnell, Christopher J; Nieminen, Markku S; Nickerson, Deborah A; Montgomery, Grant W; Meitinger, Thomas; McPherson, Ruth; McCarthy, Mark I; McArdle, Wendy; Masson, David; Martin, Nicholas G; Marroni, Fabio; Mangino, Massimo; Magnusson, Patrik K E; Lucas, Gavin; Luben, Robert; Loos, Ruth J F; Lokki, Marja-Liisa; Lettre, Guillaume; Langenberg, Claudia; Launer, Lenore J; Lakatta, Edward G; Laaksonen, Reijo; Kyvik, Kirsten O; Kronenberg, Florian; König, Inke R; Khaw, Kay-Tee; Kaprio, Jaakko; Kaplan, Lee M; Johansson, Asa; Jarvelin, Marjo-Riitta; Janssens, A Cecile J W; Ingelsson, Erik; Igl, Wilmar; Kees Hovingh, G; Hottenga, Jouke-Jan; Hofman, Albert; Hicks, Andrew A; Hengstenberg, Christian; Heid, Iris M; Hayward, Caroline; Havulinna, Aki S; Hastie, Nicholas D; Harris, Tamara B; Haritunians, Talin; Hall, Alistair S; Gyllensten, Ulf; Guiducci, Candace; Groop, Leif C; Gonzalez, Elena; Gieger, Christian; Freimer, Nelson B; Ferrucci, Luigi; Erdmann, Jeanette; Elliott, Paul; Ejebe, Kenechi G; Döring, Angela; Dominiczak, Anna F; Demissie, Serkalem; Deloukas, Panagiotis; de Geus, Eco J C; de Faire, Ulf; Crawford, Gabriel; Collins, Francis S; Chen, Yii-der I; Caulfield, Mark J; Campbell, Harry; Burtt, Noel P; Bonnycastle, Lori L; Boomsma, Dorret I; Boekholdt, S Matthijs; Bergman, Richard N; Barroso, Inês; Bandinelli, Stefania; Ballantyne, Christie M; Assimes, Themistocles L; Quertermous, Thomas; Altshuler, David; Seielstad, Mark; Wong, Tien Y; Tai, E-Shyong; Feranil, Alan B; Kuzawa, Christopher W; Adair, Linda S; Taylor, Herman A; Borecki, Ingrid B; Gabriel, Stacey B; Wilson, James G; Holm, Hilma; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Krauss, Ronald M; Mohlke, Karen L; Ordovas, Jose M; Munroe, Patricia B; Kooner, Jaspal S; Tall, Alan R; Hegele, Robert A; Kastelein, John J P; Schadt, Eric E; Rotter, Jerome I; Boerwinkle, Eric; Strachan, David P; Mooser, Vincent; Stefansson, Kari; Reilly, Muredach P; Samani, Nilesh J; Schunkert, Heribert; Cupples, L Adrienne; Sandhu, Manjinder S; Ridker, Paul M; Rader, Daniel J; van Duijn, Cornelia M; Peltonen, Leena; Abecasis, Gonçalo R; Boehnke, Michael; Kathiresan, Sekar

2010-08-05

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

In vitro production of beta-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin:cholester acyltransferase, cholesterylester transfer proteins and lipoprotein lipase.

PubMed

Chung, B H; Segrest, J P; Franklin, F

1998-12-01

As a model for the formation of beta-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoproteins in fresh plasma were interacted in vitro with endogenous lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C for 18 h resulted in (1) esterification of about 45% plasma unesterified cholesterol (UC), (2) a marked increase in cholesterylester (CE) (+129%) and a decrease in triglyceride (TG) (-45%) in VLDL, and (3) a marked increase of TG (+ 341%) with a small net decrease of CE (-3.6%) in LDL, causing a significant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (from 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCAT and CETP-reacted plasma by LpL, which hydrolyzed >90% of VLDL-TG and about 50-60% of LDL-TG, converted most of VLDL in control plasma (>85%) but less than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LDL density fraction and transformed the large, buoyant LDL in the LCAT and CETP-reacted plasma into particles smaller and denser than those in the control plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained apo B-100 and E but little or no detectable apo Cs and consisted of particles having pre-beta and beta-electrophoretic mobilities. The inhibition of LCAT during incubation of plasma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density region but lowered the extent of alteration in the size and density of LDL. The LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normolipidemic fasting plasma were less pronounced than that in mildly HTG plasma, but they became highly pronounced upon increase of its TG-rich lipoprotein level by the addition of preisolated VLDL or by the induction of postprandial lipemia. Although the effect of LCAT, CETP and LpL reactions in non-circulating plasma in vitro may be different from that in vivo, the above data suggests that the plasma TG-rich lipoprotein level and the extent of intraplasma LCAT, CETP, LpL and likely hepatic lipase (HL) reactions in vivo may play a role in determining the LDL phenotype.

Interpreting Multiple Logistic Regression Coefficients in Prospective Observational Studies

DTIC Science & Technology

1982-11-01

TG HDL -C Males T-C 50-80 MRW pɘ.05 pɘ.10 1HDL-C = high density lipoprotein cholesterol MRW...consider a more complete analy- sis, attempting to uncover the relationship between CHD and TG controlling for covariables such a high density ...for T-C can be re- duced, when among older individuals, elevated T-C may increase the capacity to carry cholesterol in the high density lipoprotein

[Primary prevention of cardiovascular diseases: long term results of five year long preventive intervention in 12-year old boys (ten year prospective study)].

PubMed

Rozanov, V B; Aleksandov, A A; Shugaeva, E N; Perova, N V; Maslennikova, G Ia; Smirnova, S G; Olfer'ev, A M

2007-01-01

In a longitudinal cohort (prevention group, n=213, comparison group, n=163) of 10-year prospective follow-up we addressed efficacy of 5-year-long multifactor preventive intervention, conducted in a sample of population of 12 year old boys. Preventive intervention was carried out both at populational level and among persons with risk factors of development of cardiovascular diseases with the use of group, individual, and partly family approaches, and was directed at rationalization of nutrition, elevation of physical activity and prevention of harmful habits. During first 3 years of prevention we succeeded to achieve stable statistically significant lowering of mean levels of total cholesterol, low density lipoprotein cholesterol, triglycerides, and atherogeneity index, as well as to affect fatty component of body mass (skinfold thickness). Long term effect of 5-year long preventive intervention manifested as significantly lower level of systolic blood pressure, lower prevalence of low levels of high density lipoprotein cholesterol, smaller increment of low density lipoprotein cholesterol and index of atherogeneity in the prevention group. These results evidence that prevention of main factors of risk of development of cardiovascular diseases (obesity, arterial hypertension, disorders of lipid composition of the blood, and low physical activity) in child and adolescent age in the period of active growth and development is feasible, effective, safe and is able to lead to decrease of levels of these factors in adults, but should last uninterruptedly until formation of stable habits of healthy life style.

Total and High-Density Lipoprotein Cholesterol in Adults with Mental Retardation.

ERIC Educational Resources Information Center

Rimmer, James H.; Kelly, Luke E.

1990-01-01

The study evaluated the total cholesterol and high density lipoprotein cholesterol of 40 adults (mean age 37.5 years) with mental retardation residing at an intermediate care facility. Results indicated that 59 percent of the males and 68 percent of the females were at moderate to high risk for coronary heart disease. (DB)

Serum Cholesterol Levels in College Students: Opportunities for Education and Intervention.

ERIC Educational Resources Information Center

Sparling, Phillip B.; Snow, Teresa K.; Beavers, Bill D.

1999-01-01

Analyzed lipid profiles in 1,088 college students at a university where lipid profiles were available to students in selected health/wellness courses. Mean total cholesterol levels were similar for men and women, but men had significantly lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol than women. About 11…

Lipoproteins during the estrous cycle in swine.

PubMed

Liu, Ying; Rector, R Scott; Thomas, Tom R; Taylor, Julia A; Holiman, Denise A; Henderson, Kyle K; Welshons, Wade V; Sturek, Michael S

2004-02-01

The purpose of this study was to examine lipoprotein values at high versus low 17beta-estradiol (E2) concentrations in Yucatan miniature swine. Estrous cycles were measured by heat checking the female on a daily basis using a boar. All swine were fed a 1,050-g low-fat, standard chow diet (8% kcal from fat) once per day. Fasted (24 hours) blood samples were collected during low (early luteal, day 5) and high (late follicular, day 18) E2 concentrations to determine differences in concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein cholesterol (HDL-C), and subfractions. Concentrations of E2 differed significantly from day 5 (3.5 +/- 0.7 pg/mL) to day 18 (14.2 +/- 1.8 pg/mL) of the estrous cycle. Except for HDL(3)-C, all lipoprotein parameters examined were significantly elevated during high E2 versus low E2. TC/HDL-C and LDL-C/HDL-C ratios were significantly lower during the high E2 phase. These results suggest that lipoprotein concentrations fluctuate during the estrous cycle of swine, with high E2 concentrations associated with elevated lipoprotein concentrations.

Hemoglobin level and lipoprotein particle size.

PubMed

Hämäläinen, Päivi; Saltevo, Juha; Kautiainen, Hannu; Mäntyselkä, Pekka; Vanhala, Mauno

2018-01-10

Alterations in lipoprotein size are associated with increased cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk of atherosclerosis and was previously associated with obesity, metabolic syndrome, and insulin resistance. No previous studies have investigated an association between hemoglobin concentration and lipoprotein particle size. We conducted a population-based, cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) born in Pieksämäki, Finland, who were categorized into five age groups. The concentrations and sizes of lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic resonance (NMR) spectroscopy. Larger very low density lipoprotein (VLDL) particle diameter was associated with higher hemoglobin concentrations in men (p = 0.003). There was a strong relationship between smaller high density lipoprotein (HDL) particle size and higher hemoglobin concentration in both men and women as well as with smaller low density lipoprotein (LDL) particle size and higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p = 0.008). VLDL particle concentration had a moderate positive correlation with hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed a statistical trend suggesting increasing particle concentration with increasing hemoglobin levels (r = 0.08; p = 0.05). Higher hemoglobin levels are associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and increasing amounts of larger VLDL and smaller LDL particles. This suggests that a higher hemoglobin concentration is associated with an unfavorable lipoprotein particle profile that is part of states that increase cardiovascular disease risk like diabetes and metabolic syndrome.

Pharmacological Effects of Niacin on Acute Hyperlipemia.

PubMed

la Paz, Sergio Montserrat-de; Bermudez, Beatriz; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

2016-01-01

The well-known changes in modern lifestyle habits including over nutrition and physical inactivity have led to striking adverse effects on public health (e.g., obesity, diabetes, and metabolic syndrome) over recent decades. One noticeable consequence is exaggerated and prolonged state of postprandial hyperlipemia due to the ingestion of multiple fat-enriched meals during the course of a day. Postprandial (non-fasting) hyperlipemia is characterized by increased blood levels of exogenous triglycerides (TG) in the form of apolipoprotein (apo) B48-containing TG-rich lipoproteins (TRL), which have a causal role in the pathogenesis and progression of cardiovascular disease (CVD). The cardiovascular benefits of lifestyle modification (healthy diet and exercise) and conventional lipid-lowering therapies (e.g., statins, fibrates, and niacin) could involve their favourable effects on postprandial metabolism. Pharmacologically, niacin has been used as an athero-protective drug for five decades. Studies have since shown that niacin may decrease fasting levels of plasma verylow- density lipoproteins (VLDL), low-density lipoprotein cholesterol (LDL-C), and lipoprotein [a] (Lp[a]), while may increase high-density lipoprotein cholesterol (HDL-C). Herein, the purpose of this review was to provide an update on effects and mechanisms related to the pharmacological actions of niacin on acute hyperlipemia.

Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia.

PubMed

Razavi, Seyed-Mostafa; Gholamin, Sharareh; Eskandari, Ali; Mohsenian, Nakta; Ghorbanihaghjo, Amir; Delazar, Abbas; Rashtchizadeh, Nadereh; Keshtkar-Jahromi, Maryam; Argani, Hassan

2013-03-01

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Yanhong; Chen Kuanghueih; Gao Wei

2007-11-16

Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE{sup -/-} mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% andmore » 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury.« less

Liver Histology During Mipomersen Therapy for Severe Hypercholesterolemia

PubMed Central

Hashemi, Nikroo; Odze, Robert D.; McGowan, Mary P.; Santos, Raul D.; Stroes, Erik S.G.; Cohen, David E.

2014-01-01

Background Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein (apo) B synthesis and lowers plasma low density lipoprotein (LDL) cholesterol even in the absence of LDL receptor function, presumably due to the inhibition of hepatic production of triglyceride-rich very low density lipoprotein (VLDL) particles. By virtue of this mechanism, mipomersen therapy commonly results in the development of hepatic steatosis. Because this is frequently accompanied by alanine aminotransferase (ALT) elevations, concern has arisen that mipomersen could promote the development of steatohepatitis, which could in turn lead to fibrosis and cirrhosis over time. Objective The objective of this study was to assess the liver biopsy findings in patients treated with mipomersen. Methods We describe 7 patients who underwent liver biopsy during the mipomersen clinical development programs. Liver biopsies were reviewed by a single, blinded pathologist. Results The histopathological features were characterized by simple steatosis, without significant inflammation or fibrosis. Conclusion These findings suggest that hepatic steatosis due to mipomersen is distinct from non-alcoholic steatohepatitis. PMID:25499943

Dyslipidemia in subclinical hypothyroidism requires assessment of small dense low density lipoprotein cholesterol (sdLDL-C).

PubMed

Saric, Maida Seferovic; Jurasic, Miljenka-Jelena; Sovic, Slavica; Kranjcec, Bojana; Glivetic, Tatjana; Demarin, Vida

2017-09-26

Usually both hypothyroidism and hyperthyroidism are related to the cardiovascular and cerebrovascular disease development. The relationship between subclinical hypothyroidism has been widely investigated but the findings remain controversial. The aim of the present study was to evaluate the lipid profile in patients with subclinical hypothyroidism (SHypo) in comparison to controls and to determine the association of SHypo and dyslipidemia in attempt to find importance of small dense low-density lipoprotein cholesterol (sdLDL-C) in atherosclerosis. In this study we included 100 women, aged 30 to 70 years that were divided into subgroups according to their age. According to the values of levels of thyroid hormones they were divided into euthyroid (control) group (n = 64) and (newly discovered) subclinical hypothyroidism (SHypo) group (n = 36). A high-sensitivity C-reactive protein (hs-CRP) and lipid profile, including small dense low-density lipoprotein cholesterol (sdLDL-C) were determined. Body weight and height were measured and BMI calculated. History of the current illness, medication, alcohol consumption and cigarettes smoking were noted. Changed lipid profile as well as elevated triglycerides and sdLDL-C were observed in the group with subclinical hypothyroidism compared to the control group. It is important to determine serum lipid levels, especially serum sdLDL-C levels at an early stage of subclinical hypothyroidism, since they represent atherogenic LDL particles and are better indicators for dyslipidaemia in subclinical hypothyroidism and the development of atherosclerosis with potential complications such as cardiovascular and cerebrovascular diseases.

Metabolomics reveals the sex-specific effects of the SORT1 low-density lipoprotein cholesterol locus in healthy young adults.

PubMed

Klein, Matthias S; Connors, Kimberly E; Shearer, Jane; Vogel, Hans J; Hittel, Dustin S

2014-11-07

Metabolite profiles of individuals possessing either the cardiovascular risk or protective variants of the low-density lipoprotein cholesterol (LDL-C) associated 1p13.3 locus of the SORT1 gene (rs646776) were analyzed. Serum metabolites and lipids were assessed using LC-MS-based metabolomics in a healthy young population (n = 138: 95 males, 43 females). Although no significant differences were observed in the combined cohort, divergent sex effects were identified. Females carrying the protective allele showed increased phosphatidylcholines, very long chain fatty acids (>C20), and unsaturated fatty acids. Unsaturated fatty acids are considered to be protective against cardiovascular disease. In contrast, males carrying the protective allele exhibited decreased long-chain fatty acids (≤C20) and sphingomyelins, which is similarly considered to decrease cardiovascular disease risk. No significant changes in clinically assessed lipids such as LDL-C, high-density lipoprotein (HDL-C), total cholesterol, or triglycerides were observed in females, whereas only LDL-C was significantly changed in males. This indicates that, apart from reducing LDL-C, other mechanisms may contribute to the protective effect of the SORT1 locus. Thus, the analysis of metabolic biomarkers might reveal early disease development that may be overlooked by relying on standard clinical parameters.

Effects of insulin-like growth factor-1 on the assembly and secretion of very low-density lipoproteins in cow hepatocytes in vitro.

PubMed

Li, Xinwei; Guan, Yuan; Li, Ying; Wu, Dianjun; Liu, Lei; Deng, Qinghua; Li, Xiaobing; Wang, Zhe; Liu, Guowen

2016-01-15

Fatty liver is a major metabolic disorder of dairy cows. One important reason is that hepatic very low-density lipoproteins (VLDL) assembly was significant decreased in dairy cows with fatty liver. In addition, the impairment of insulin-like growth factor (IGF)-1 synthesis was involved in the development of fatty liver. Therefore, the objective of this study was to investigate the effects of IGF-1 on the VLDL assembly in cow hepatocytes. In this study, cow hepatocytes were cultured and then transfected with Ad-GFP-IGF-1 (inhibited the IGF-1 expression) and Ad-GFP (negative control), and treated with different concentrations of IGF-1, respectively. The results showed that IGF-1 increased the mRNA abundance of apolipoprotein B100 (ApoB100), apolipoprotein E (ApoE), microsomal triglyceride transfer protein (MTTP), and low-density lipoprotein receptor (LDLR) and then increased the VLDL assembly in cow hepatocytes. Nevertheless, impairment of IGF-1 expression by Ad-GFP-IGF-1 could inhibit above genes expression and VLDL assembly in hepatocytes. Taken together, these results indicate that IGF-1 increases the VLDL assembly and impairment of IGF-1 expression decreases the VLDL assembly in cow hepatocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically defined disease in post-menopausal women

USDA-ARS?s Scientific Manuscript database

The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women. Plasma HDL subpopulation concentrations, quantified by 2-dimensional gel electrophoresis...

Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops).

PubMed

Chauke, Chesa G; Arieff, Zainunisha; Kaur, Mandeep; Seier, Jurgen V

2014-02-01

Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.

Low-density lipoprotein receptor-negative compound heterozygous familial hypercholesterolemia: Two lifetime journeys of lipid-lowering therapy.

PubMed

Yahya, Reyhana; Mulder, Monique T; Sijbrands, Eric J G; Williams, Monique; Roeters van Lennep, Jeanine E

We present the case history of 2 patients with low-density lipoprotein receptor-negative compound heterozygous familial hypercholesterolemia who did not receive lipoprotein apheresis. We describe the subsequent effect of all lipid-lowering medications during their life course including resins, statins, ezetimibe, nicotinic acid/laropiprant, mipomersen, and lomitapide. These cases tell the story of siblings affected with this rare disease, who are free of symptoms but still are at a very high cardiovascular disease risk, and their treatment from childhood. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The low density lipoprotein receptor-related protein 1: Unique tissue-specific functions revealed by selective gene knockout studies

PubMed Central

Lillis, Anna P.; Van Duyn, Lauren B.; Murphy-Ullrich, Joanne E.; Strickland, Dudley K.

2008-01-01

The low-density lipoprotein (LDL) receptor-related protein (originally called LRP, but now referred to as LRP1) is a large endocytic receptor that is widely expressed in several tissues. LRP1 is a member of the LDL receptor family that plays diverse roles in various biological processes including lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes and cellular entry of bacterial toxins and viruses. Deletion of the LRP1 gene leads to lethality in mice, revealing a critical, but as of yet, undefined role in development. Tissue-specific gene deletion studies reveal an important contribution of LRP1 in the vasculature, central nervous system, in macrophages and in adipocytes. Three important properties of LRP1 dictate its diverse role in physiology: first, its ability to recognize more than thirty distinct ligands; second, its ability to bind a large number of cytoplasmic adaptor proteins via determinants located on its cytoplasmic domain in a phosphorylation-specific manner; and third, its ability to associate with and modulate the activity of other transmembrane receptors such as integrins and receptor tyrosine kinases. PMID:18626063

An overview of the new frontiers in the treatment of atherogenic dyslipidemias.

PubMed

Rached, F H; Chapman, M J; Kontush, A

2014-07-01

Cardiovascular diseases (CVDs) are the leading cause of morbidity/mortality worldwide. Dyslipidemia is a major risk factor for premature atherosclerosis and CVD. Lowering low-density-lipoprotein cholesterol (LDL-C) levels is well established as an intervention for the reduction of CVDs. Statins are the first-line drugs for treatment of dyslipidemia, but they do not address all CVD risk. Development of novel therapies is ongoing and includes the following: (i) reduction of LDL-C concentrations using antibodies to proprotein convertase subtilisin/kexin-9, antisense oligonucleotide inhibitors of apolipoprotein B production, microsomal transfer protein (MTP) inhibitors, and acyl-coenzyme A cholesterol acyl transferase inhibitors; (ii) reduction in levels of triglyceride-rich lipoproteins with ω-3 fatty acids, MTP inhibitors, and diacylglycerol acyl transferase-1 inhibitors; and (iii) increase of high-density-lipoprotein (HDL) cholesterol levels, HDL particle numbers, and/or HDL functionality using cholesteryl ester transfer protein inhibitors, HDL-derived agents, apolipoprotein AI mimetic peptides, and microRNAs. Large prospective outcome trials of several of these emerging therapies are under way, and thrilling progress in the field of lipid management is anticipated.

Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor-containing highly active antiretroviral therapy.

PubMed

Koppel, Kristina; Bratt, Göran; Schulman, Sam; Bylund, Håkan; Sandström, Eric

2002-04-15

Decreased insulin sensitivity, hyperlipidemia, and body fat changes are considered as risk factors for coronary heart disease (CHD). A clustering of such factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired fibrinolysis and increased coagulation are additional independent risk factors for CHD. We studied the effects of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in 363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and 97 were treatment naive. The fasting plasma levels of insulin, glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and fibrinogen were evaluated together with the areas of visceral adipose tissue and the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol; visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were significantly increased in patients receiving PI-containing HAART compared with treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly higher in patients receiving PI-containing HAART. PAI-1 levels were higher in individuals with MSDR but also in patients without MSDR who were receiving PI-containing HAART. PAI-1 was independently correlated to use of PI-containing HAART, triglyceride level, insulin level, and body mass index (p <.001). These findings suggest that patients receiving PI-containing HAART have decreased fibrinolysis and increased coagulability, which may thus represent additional risk factors for cardiovascular disease in this patient group.

Association of socioeconomic stratification with plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children.

PubMed

Ruiz-Fernández, Nelina; Bosch, Virgilio; Giacopini, Maria Isabel

2016-12-30

To establish association between socioeconomic status and plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children from the middle-class and in critical poverty. Cross-sectional study with a sample of 114 school-age children (aged 7-9). The socioeconomic status, dietary intake of macro and micro-nutrients, weight, height, lipid profile, indicators of lipid peroxidation and enzymatic and non-enzymatic antioxidants were determined. The daily average intake of energy, carbohydrates and vitamin A, and the percentage of energy obtained from carbohydrates was significantly higher in middle-class children compared to critical poverty children ( p <0.05). The circulating oxidized low density lipoprotein ( p <0.001) and the susceptibility of low density lipoproteins and very low density lipoproteins to oxidation in vitro ( p <0.05) were significantly higher in middle-class children, while the critical poverty children showed significantly lower levels of Vitamin C and E in plasma ( p <0.05). Non-enzymatic antioxidant levels were frequently deficient in both strata. The concentrations of circulating oxidized low density lipoprotein (OR: 1.09, CI 95% : 1.016-1.179; p = 0.017) and Vitamin C (OR: 3.21, CI 95% : 1.104-9.938; p = 0.032) were associated to the socioeconomic status independently of gender, family history of premature coronary artery disease, triglicerides, Vitamin C and E dietary intake and count of white blood cells. The socioeconomic status was associated to circulating oxidized low density lipoprotein and Vitamin C in Venezuelan school-age children, The results suggested the need to improve the dietary intake of antioxidants in both studied socioeconomic groups.

Negatively Cooperative Binding of High Density Lipoprotein to the HDL Receptor SR-BI†

PubMed Central

Nieland, Thomas J.F.; Xu, Shangzhe; Penman, Marsha; Krieger, Monty

2011-01-01

Scavenger receptor class B, type I (SR-BI) is a high-density lipoprotein (HDL) receptor, which also binds low density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. SR-BI also is a co-receptor for hepatitis C virus and a signaling receptor that regulates cell metabolism. Many investigators have reported that lipoproteins bind to SR-BI via a single class of independent (not interacting), high affinity binding sites (one site model). We have re-investigated the ligand concentration dependence of 125I-HDL binding to SR-BI and SR-BI-mediated specific uptake of [3H]CE from [3H]CE-HDL using an expanded range of ligand concentrations (<1 µg protein/ml, lower than previously reported). Scatchard and non-linear least squares model fitting analyses of the binding and uptake data were both inconsistent with a single class of independent binding sites binding univalent lipoprotein ligands. The data are best fit by models in which SR-BI has either two independent classes of binding sites, or one class of sites exhibiting negative cooperativity due to either classic allostery or ensemble effects (‘ lattice model’). Similar results were observed for LDL. Application of the ‘infinite dilution’ dissociation rate method established that the binding of 125I-HDL to SR-BI at 4 °C exhibits negative cooperativity. The unexpected complexity of the interactions of lipoproteins with SR-BI should be taken into account when interpreting the results of experiments that explore the mechanism(s) by which SR-BI mediates ligand binding, lipid transport and cell signaling. PMID:21254782

Decreased cholesterol efflux capacity and atherogenic lipid profile in young women with PCOS.

PubMed

Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Rader, Daniel; Playford, Martin; Mehta, Nehal N; Dokras, Anuja

2014-05-01

Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. A case control study was performed at an academic PCOS center. Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study. The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy. Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.

Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in Young Women With PCOS

PubMed Central

Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Rader, Daniel; Playford, Martin; Mehta, Nehal N.

2014-01-01

Context: Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD. Objective: The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk. Design and Setting: A case control study was performed at an academic PCOS center. Patients: Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study. Main Outcome Measures: The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy. Results: Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). Conclusions: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population. PMID:24512495

Association of ADRB2 polymorphism with triglyceride levels in Tongans

PubMed Central

2013-01-01

Background Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. Methods To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. Results A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Conclusions In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index. PMID:23875540

Staphylococcus aureus utilizes host-derived lipoprotein particles as sources of exogenous fatty acids.

PubMed

Delekta, Phillip C; Shook, John C; Lydic, Todd A; Mulks, Martha H; Hammer, Neal D

2018-03-26

Methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health. Consequently, much effort has focused on the development of new antimicrobials that target novel aspects of S. aureus physiology. Fatty acids are required to maintain cell viability, and bacteria synthesize fatty acids using the type II fatty acid synthesis pathway (FASII). FASII is significantly different from human fatty acid synthesis, underscoring the therapeutic potential of inhibiting this pathway. However, many Gram-positive pathogens incorporate exogenous fatty acids, bypassing FASII inhibition and leaving the clinical potential of FASII inhibitors uncertain. Importantly, the source(s) of fatty acids available to pathogens within the host environment remains unclear. Fatty acids are transported throughout the body by lipoprotein particles in the form of triglycerides and esterified cholesterol. Thus, lipoproteins, such as low-density lipoprotein (LDL) represent a potentially rich source of exogenous fatty acids for S. aureus during infection. We sought to test the ability of LDLs to serve as a fatty acid source for S. aureus and show that cells cultured in the presence of human LDLs demonstrate increased tolerance to the FASII inhibitor, triclosan. Using mass spectrometry, we observed that host-derived fatty acids present in the LDLs are incorporated into the staphylococcal membrane and that tolerance to triclosan is facilitated by the fatty acid kinase A, FakA, and Geh, a triacylglycerol lipase. Finally, we demonstrate that human LDLs support the growth of S. aureus fatty acid auxotrophs. Together, these results suggest that human lipoprotein particles are a viable source of exogenous fatty acids for S. aureus during infection. IMPORTANCE Inhibition of bacterial fatty acid synthesis is a promising approach to combating infections caused by S. aureus and other human pathogens. However, S. aureus incorporates exogenous fatty acids into its phospholipid bilayer. Therefore, the clinical utility of targeting bacterial fatty acid synthesis is debated. Moreover, the fatty acid reservoir(s) exploited by S. aureus are not well understood. Human low-density lipoprotein particles represent a particularly abundant in vivo source of fatty acids and are present in tissues S. aureus colonizes. Herein, we establish that S. aureus is capable of utilizing the fatty acids present in low-density lipoproteins to bypass both chemical and genetic inhibition of fatty acid synthesis. These findings imply that S. aureus targets LDLs as a source of fatty acids during pathogenesis. Copyright © 2018 American Society for Microbiology.

Metabolic profiling of fatty liver in young and middle‐aged adults: Cross‐sectional and prospective analyses of the Young Finns Study

PubMed Central

Würtz, Peter; Suomela, Emmi; Lehtovirta, Miia; Kangas, Antti J.; Jula, Antti; Mikkilä, Vera; Viikari, Jorma S.A.; Juonala, Markus; Rönnemaa, Tapani; Hutri‐Kähönen, Nina; Kähönen, Mika; Lehtimäki, Terho; Soininen, Pasi; Ala‐Korpela, Mika; Raitakari, Olli T.

2016-01-01

Nonalcoholic fatty liver is associated with obesity‐related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis‐related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty‐eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population‐based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34‐49 years (19% prevalence). Cross‐sectional associations as well as 4‐year and 10‐year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age‐adjusted and sex‐adjusted cross‐sectional analyses). The strongest direct associations were observed for extremely large very‐low‐density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48‐6.78), other very‐low‐density lipoprotein measures, and branched‐chain amino acids (e.g., leucine OR = 2.94, 2.51‐3.44). Strong inverse associations were observed for high‐density lipoprotein measures, e.g., high‐density lipoprotein size (OR = 0.36, 0.30‐0.42) and several fatty acids including omega‐6 (OR = 0.37, 0.32‐0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491‐500). PMID:27775848

ASYMMETRIC DIMETHYLARGININE LEVELS AND ATHEROSCLEROSIS MARKERS IN CUSHING SYNDROME.

PubMed

Ozsurekci, Cemile Gulbas; Akturk, Mujde; Ozkan, Cigdem; Gulbahar, Ozlem; Altinova, Alev Eroglu; Yalcin, Muhittin; Arslan, Emre; Toruner, Fusun

2016-09-01

As a consequence of hypercortisolism, Cushing syndrome (CS) is frequently observed with other diseases that are associated with atherosclerosis, including diabetes mellitus, dyslipidemia, hypertension, and obesity. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in CS. We investigate CVD risk markers such as asymmetric dimethylarginine (ADMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), highsensitive C-reactive protein (hsCRP), homocysteine, lipid levels, ankle-brachial index (ABI), and carotid intimamedia thickness (CIMT) in CS. Our study included 27 patients with CS and 27 age-, sex-, body mass index (BMI)-, and comorbid disease-matched control subjects. Plasma ADMA levels were significantly lower in the CS group than the control group (P = .013). Total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and apolipoprotein A1 and apolipoprotein B levels were higher in patients with CS than the control group (P<.05). We did not find any statistically significant differences in levels of hsCRP, Lp-PLA2, or homocysteine or CIMT and ABI measurements between the CS group and comorbidity-matched control group (P>.05). We found that ADMA levels were lower in CS, the finding that should be further investigated. Levels of hsCRP, Lp-PLA2, and homocysteine levels and CIMT and ABI measurements were similar between the CS group and comorbidity-matched control group. None of these markers was prominent to show an increased risk of CVD in CS, independent of the comorbidities of CS. ABI = ankle-brachial index Apo = apolipoprotein ADMA = asymmetric dimethylarginine BMI = body mass index CVD = cardiovascular disease CIMT = carotid intima-media thickness CS = Cushing syndrome DM = diabetes mellitus DDAH = dimethylarginine dimethylaminohydrolase ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein hsCRP = high-sensitive C-reactive protein HOMA-IR = homeostatic model assessment of insulin resistance HT = hypertension LDL = low-density lipoprotein Lp-PLA2 = lipoprotein-associated phospholipase A2 Lp-a = lipoprotein a NO = nitric oxide.

Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

PubMed Central

Srivastava, Anand; Adams-Huet, Beverley; Vega, Gloria L; Toto, Robert D

2016-01-01

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo −24.6%, los −38.2%, spiro −51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (−20.9% vs +34.3%, p<0.01), V+I C(−18.8% vs +21.3%, p<0.01), and V+I-ApoB (−13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. Trial registration number NCT00381134; Results. PMID:27388615

Emerging LDL therapies: Mipomersen-antisense oligonucleotide therapy in the management of hypercholesterolemia.

PubMed

Toth, Peter P

2013-01-01

Familial hypercholesterolemia (FH) is characterized by severe elevations in low-density lipoprotein cholesterol (LDL-C) and poses considerable treatment challenges. Substantive LDL-C reductions are difficult to achieve with standard therapies, and many patients with FH do not tolerate currently available lipid-lowering medications. Mipomersen is an antisense oligonucleotide injectable drug that was recently approved by the Food and Drug Administration for the treatment of homozygous FH. It is complementary in sequence to a segment of the human apolipoprotein (Apo) B-100 messenger RNA and specifically binds to it, blocking translation of the gene product. Reducing the production of Apo B-100 reduces hepatic production of very low-density lipoprotein, consequently decreasing circulating levels of atherogenic very low-density lipoprotein remnants, intermediate-density lipoproteins, LDL, and lipoprotein(a) particles. Results from a pivotal trial conducted in patients with homozygous FH, and supporting trials in patients with heterozygous FH with coronary artery disease (CAD) (LDL-C ≥ 100 mg/dL, triglycerides < 200 mg/dL), severe hypercholesterolemia (LDL-C ≥ 300 mg/dL or ≥ 200 mg/dL with CAD), and individuals at high risk for CAD (LDL-C ≥ 100 mg/dL, triglycerides ≤ 200 mg/dL), have indicated that mipomersen reduces all Apo B-containing atherogenic lipoproteins. The average LDL-C reduction was >100 mg/dL in homozygous FH and severe hypercholesterolemia populations. The main on-treatment adverse events were mild-to-moderate injection site reactions and flu-like symptoms. Available data regarding the efficacy, safety and tolerability of mipomersen, including results at up to 104 weeks of therapy, support the use of mipomersen for the treatment of FH. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: A post hoc analysis of the AIM-HIGH trial.

PubMed

Otvos, James D; Guyton, John R; Connelly, Margery A; Akapame, Sydney; Bittner, Vera; Kopecky, Steven L; Lacy, Megan; Marcovina, Santica M; Muhlestein, Joseph B; Boden, William E

The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial showed no incremental benefit of extended-release niacin (ERN) therapy added to simvastatin in subjects with cardiovascular disease (CVD). To examine the effects of ERN treatment on lipoprotein particles and GlycA, a new marker of systemic inflammation, and their relations with incident CVD events including mortality. GlycA and very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle subclasses were quantified by nuclear magnetic resonance spectroscopy using available stored baseline (n = 2754) and 1-year in-trial (n = 2581) samples. Associations with CVD events and all-cause mortality were assessed using multivariable Cox proportional hazards regression adjusted for age, sex, diabetes, treatment assignment, and lipoproteins. Compared to placebo, ERN treatment lowered very low-density lipoprotein and LDL and increased HDL particle concentrations, increased LDL and HDL particle sizes (all P < .0001), but did not affect GlycA. Baseline and in-trial GlycA levels were associated with increased risk of CVD events: hazard ratio (HR) per SD increment, 1.17 (95% confidence interval [CI], 1.06-1.28) and 1.13 (1.02-1.26), respectively. However, none of the lipoprotein particle classes or subclasses was associated with incident CVD. By contrast, all-cause mortality was significantly associated with both GlycA (baseline HR: 1.46 [1.22-1.75]; in-trial HR: 1.41 [1.24-1.60]) and low levels of small HDL particles (baseline HR: 0.69 [0.56-0.86]; in-trial HR: 0.69 [0.56-0.86]). This Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial post hoc substudy indicates that inflammation, as indexed by GlycA, is unaffected by ERN treatment but is significantly associated with the residual risk of CVD and death in patients treated to low levels of LDL cholesterol. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Impact of hormonal contraception and weight loss on high-density lipoprotein cholesterol efflux and lipoprotein particles in women with polycystic ovary syndrome.

PubMed

Dokras, Anuja; Playford, Martin; Kris-Etherton, Penny M; Kunselman, Allen R; Stetter, Christy M; Williams, Nancy I; Gnatuk, Carol L; Estes, Stephanie J; Sarwer, David B; Allison, Kelly C; Coutifaris, Christos; Mehta, Nehal; Legro, Richard S

2017-05-01

To study the effects of oral contraceptive pills (OCP), the first-line treatment for PCOS, on high-density lipoprotein cholesterol (HDL-C) function (reverse cholesterol efflux capacity) and lipoprotein particles measured using nuclear magnetic resonance spectroscopy in obese women. Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive Lifestyle modification) or Combined (OCP + Lifestyle) treatment groups for 16 weeks. Eighty-seven overweight/obese women with PCOS at two academic centres. Change in HDL-C efflux capacity and lipoprotein particles. High-density lipoprotein cholesterol efflux capacity increased significantly at 16 weeks in the OCP group [0·11; 95% confidence interval (CI) 0·03, 0·18, P = 0·008] but not in the Lifestyle (P = 0·39) or Combined group (P = 0·18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0·09; 95% CI 0·01, 0·15; P = 0·01). Change in HDL-C efflux correlated inversely with change in serum testosterone (r s = -0·21; P = 0·05). In contrast, OCP use induced an atherogenic low-density lipoprotein cholesterol (LDL-C) profile with increase in small (P = 0·006) and large LDL-particles (P = 0·002). Change in small LDL-particles correlated with change in serum testosterone (r s = -0·31, P = 0·009) and insulin sensitivity index (ISI; r s = -0·31, P = 0·02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL particles. Oral contraceptive pills use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes. © 2017 John Wiley & Sons Ltd.

Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes

PubMed Central

Engström, Gunnar; Larsson, Susanna C.; Traylor, Matthew; Markus, Hugh S.; Melander, Olle; Orho-Melander, Marju

2018-01-01

Background and Purpose— Statin therapy is associated with a lower risk of ischemic stroke supporting a causal role of low-density lipoprotein (LDL) cholesterol. However, more evidence is needed to answer the question whether LDL cholesterol plays a causal role in ischemic stroke subtypes. In addition, it is unknown whether high-density lipoprotein cholesterol and triglycerides have a causal relationship to ischemic stroke and its subtypes. Our aim was to investigate the causal role of LDL cholesterol, high-density lipoprotein cholesterol, and triglycerides in ischemic stroke and its subtypes through Mendelian randomization (MR). Methods— Summary data on 185 genome-wide lipids-associated single nucleotide polymorphisms were obtained from the Global Lipids Genetics Consortium and the Stroke Genetics Network for their association with ischemic stroke (n=16 851 cases and 32 473 controls) and its subtypes, including large artery atherosclerosis (n=2410), small artery occlusion (n=3186), and cardioembolic (n=3427) stroke. Inverse-variance–weighted MR was used to obtain the causal estimates. Inverse-variance–weighted multivariable MR, MR-Egger, and sensitivity exclusion of pleiotropic single nucleotide polymorphisms after Steiger filtering and MR-Pleiotropy Residual Sum and Outlier test were used to adjust for pleiotropic bias. Results— A 1-SD genetically elevated LDL cholesterol was associated with an increased risk of ischemic stroke (odds ratio: 1.12; 95% confidence interval: 1.04–1.20) and large artery atherosclerosis stroke (odds ratio: 1.28; 95% confidence interval: 1.10–1.49) but not with small artery occlusion or cardioembolic stroke in multivariable MR. A 1-SD genetically elevated high-density lipoprotein cholesterol was associated with a decreased risk of small artery occlusion stroke (odds ratio: 0.79; 95% confidence interval: 0.67–0.90) in multivariable MR. MR-Egger indicated no pleiotropic bias, and results did not markedly change after sensitivity exclusion of pleiotropic single nucleotide polymorphisms. Genetically elevated triglycerides did not associate with ischemic stroke or its subtypes. Conclusions— LDL cholesterol lowering is likely to prevent large artery atherosclerosis but may not prevent small artery occlusion nor cardioembolic strokes. High-density lipoprotein cholesterol elevation may lead to benefits in small artery disease prevention. Finally, triglyceride lowering may not yield benefits in ischemic stroke and its subtypes. PMID:29535274

Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis.

PubMed

Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

2010-10-01

The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis.

Simple method provides resolution of albumin, lipoprotein, free fraction, and chylomicron to enhance the utility of protein binding assays.

PubMed

Brockman, Adam H; Oller, Haley R; Moreau, Benoît; Kriksciukaite, Kristina; Bilodeau, Mark T

2015-02-12

Medicinal chemists have been encouraged in recent years to embrace high speed protein binding assays. These methods employ dialysis membranes in 96-well format or spin filters. Membrane-based methods do not separate lipoprotein binding from albumin binding and introduce interference despite membrane binding controls. Ultracentrifugation methods, in contrast, do not introduce interference if density gradients can be avoided and they resolve lipoprotein from albumin. A new generation of compact, fast ultracentrifuges facilitates the rapid and fully informative separation of plasma into albumin, albumin/fatty acid complex, lipoprotein, protein-free, and chylomicron fractions with no need of salt or sugar density gradients. We present a simple and fast ultracentrifuge method here for two platinum compounds and a taxane that otherwise bound irreversibly to dialysis membranes and which exhibited distinctive lipoprotein binding behaviors. This new generation of ultracentrifugation methods underscores a need to further discuss protein binding assessments as they relate to medicinal chemistry efforts.

Lipoprotein particle concentration measured by nuclear magnetic resonance spectroscopy is associated with gestational age at delivery: a prospective cohort study.

PubMed

Grace, M R; Vladutiu, C J; Nethery, R C; Siega-Riz, A M; Manuck, T A; Herring, A H; Savitz, D; Thorp, J T

2018-06-01

To estimate the association between lipoprotein particle concentrations in pregnancy and gestational age at delivery. Prospective cohort study. The study was conducted in the USA at the University of North Carolina. We assessed 715 women enrolled in the Pregnancy, Infection, and Nutrition study from 2001 to 2005. Fasting blood was collected at two time points (<20 and 24-29 weeks of gestation). Nuclear magnetic resonance (NMR) quantified lipoprotein particle concentrations [low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low density lipoprotein (VLDL)] and 10 subclasses of lipoproteins. Concentrations were assessed as continuous measures, with the exception of medium HDL which was classified as any or no detectable level, given its distribution. Cox proportional hazards models estimated hazard ratios (HR) for gestational age at delivery adjusting for covariates. Gestational age at delivery, preterm birth (<37 weeks of gestation), and spontaneous preterm birth. At <20 weeks of gestation, three lipoproteins were associated with later gestational ages at delivery [large LDL NMR (HR 0.78, 95% CI 0.64-0.96), total VLDL NMR (HR 0.77, 95% CI 0.61-0.98), and small VLDL NMR (HR 0.78, 95% CI 0.62-0.98], whereas large VLDL NMR (HR 1.19, 95% CI 1.01-1.41) was associated with a greater hazard of earlier delivery. At 24-28 weeks of gestation, average VLDL NMR (HR 1.25, 95% CI 1.03-1.51) and a detectable level of medium HDL NMR (HR 1.90, 95% CI 1.19-3.02) were associated with earlier gestational ages at delivery. In this sample of pregnant women, particle concentrations of VLDL NMR , LDL NMR , IDL NMR , and HDL NMR were each independently associated with gestational age at delivery for all deliveries or spontaneous deliveries <37 weeks of gestation. These findings may help formulate hypotheses for future studies of the complex relationship between maternal lipoproteins and preterm birth. Nuclear magnetic resonance spectroscopy may identify lipoprotein particles associated with preterm delivery. © 2017 Royal College of Obstetricians and Gynaecologists.

New Era of Lipid-Lowering Drugs

PubMed Central

Rye, Kerry-Anne

2016-01-01

There are several established lipid-modifying agents, including statins, fibrates, niacin, and ezetimibe, that have been shown in randomized clinical outcome trials to reduce the risk of having an atherosclerotic cardiovascular event. However, in many people, the risk of having an event remains unacceptably high despite treatment with these established agents. This has stimulated the search for new therapies designed to reduce residual cardiovascular risk. New approaches that target atherogenic lipoproteins include: 1) inhibition of proprotein convertase subtilisin/kexin type 9 to increase removal of atherogenic lipoproteins from plasma; 2) inhibition of the synthesis of apolipoprotein (apo) B, the main protein component of atherogenic lipoproteins; 3) inhibition of microsomal triglyceride transfer protein to block the formation of atherogenic lipoproteins; 4) inhibition of adenosine triphosphate citrate lyase to inhibit the synthesis of cholesterol; 5) inhibition of the synthesis of lipoprotein(a), a factor known to cause atherosclerosis; 6) inhibition of apoC-III to reduce triglyceride-rich lipoproteins and to enhance high-density lipoprotein (HDL) functionality; and 7) inhibition of cholesteryl ester transfer protein, which not only reduces the concentration of atherogenic lipoproteins but also increases the level and function of the potentially antiatherogenic HDL fraction. Other new therapies that specifically target HDLs include infusions of reconstituted HDLs, HDL delipidation, and infusions of apoA-I mimetic peptides that mimic some of the functions of HDLs. This review describes the scientific basis and rationale for developing these new therapies and provides a brief summary of established therapies. PMID:26983688

Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

PubMed

Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

2006-01-01

Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

A Mediterranean-style low-glycemic-load diet increases plasma carotenoids and decreases LDL oxidation in women with metabolic syndrome☆

PubMed Central

Barona, Jacqueline; Jones, Jennifer J.; Kopec, Rachel E.; Comperatore, Michael; Andersen, Catherine; Schwartz, Steven J.; Lerman, Robert H.; Fernandez, Maria Luz

2013-01-01

Thirty-five women with metabolic syndrome and high plasma low-density lipoprotein (LDL) cholesterol (≥100 mg/dl) participated in a dietary intervention consisting of a Mediterranean-style low-glycemic-load diet for 12 weeks. Participants were randomly allocated to consume diet only (n=15) or diet plus a medical food containing soy protein and plant sterols (n=20). Plasma concentrations of carotenoids, lipoprotein subfractions and oxidized LDL (OxLDL) were measured. Independent of treatment, women had a significant increase in plasma lutein (P<.0001) and β-carotene (P<.0001), while plasma lycopene was reduced (P<.05) after 12 weeks. Low-density lipoprotein cholesterol was reduced from 138±35 to 114±33 mg/dl (P<.0001). In addition, decreases were observed in the atherogenic subfractions: large very low-density lipoprotein (P<.05), small LDL (P<.00001) and medium high-density lipoprotein (P<.05). Oxidized LDL was significantly reduced by 12% in both groups (P<.01). Changes in OxLDL were inversely correlated with plasma lutein (r=−.478, P<.0001). The data indicate that women complied with the dietary regimen by increasing fruits and vegetable intake. Decreased consumption of high-glycemic foods frequently co-consumed with lycopene-rich tomato sauce such as pasta and pizza may be responsible for the lowering of this carotenoid in plasma after 12 weeks. These results also suggest that plasma lutein concentrations may protect against oxidative stress by reducing the concentrations of OxLDL. PMID:21775117

Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect.

PubMed

Cairoli, E; Rebella, M; Danese, N; Garra, V; Borba, E F

2012-10-01

The influence of antimalarials on lipids in systemic lupus erythematosus (SLE) has been identified in several studies but not in many prospective cohorts. The aim of this study was to longitudinally determine the effect of antimalarials on the lipoprotein profile in SLE. Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol (LDL) plasma levels were determined at entry and after 3 months of hydroxychloroquine (HCQ) treatment in a longitudinal evaluation of 24 patients with SLE. a significant decrease in TC (198 ± 33.7 vs. 183 ± 30.3 mg/dl, p = 0.023) and LDL levels (117 ± 31.3 vs. 101 ± 26.2 mg/dl, p = 0.023) were detected after the 3 months of HCQ therapy. The reduction of 7.6% in TC (p = 0.055) and 13.7% in LDL levels (p = 0.036) determined a significant decrease in the frequency of dyslipidemia (26% vs. 12.5%, p = 0.013) after HCQ therapy. This longitudinal study demonstrated the beneficial effect of antimalarials on lipids in SLE since this therapy induced a reduction of atherogenic lipoproteins.

Pyrene-Labeled Amphiphiles: Dynamic And Structural Probes Of Membranes And Lipoproteins

NASA Astrophysics Data System (ADS)

Pownall, Henry J.; Homan, Reynold; Massey, John B.

1987-01-01

Lipids and proteins are important functional and structural components of living organisms. Although proteins are frequently found as soluble components of plasma or the cell cytoplasm, many lipids are much less soluble and separate into complex assemblies that usually contain proteins. Cell membranes and plasma lipoproteins' are two important macro-molecular assemblies that contain both lipids and proteins. Cell membranes are composed of a variety of lipids and proteins that form an insoluble bilayer array that has relatively little curvature over distances of several nm. Plasma lipoproteins are different in that they are much smaller, water-soluble, and have highly curved surfaces. A model of a high density lipoprotein (HDL) is shown in Figure 1. This model (d - 10 nm) contains a surface of polar lipids and proteins that surrounds a small core of insoluble lipids, mostly triglycerides and cholesteryl esters. The low density (LDL) (d - 25 nm) and very low density (VLDL) (d 90 nm) lipoproteins have similar architectures, except the former has a cholesteryl ester core and the latter a core that is almost exclusively triglyceride (Figure 1). The surface proteins of HDL are amphiphilic and water soluble; the single protein of LDL is insoluble, whereas VLDL contains both soluble and insoluble proteins. The primary structures of all of these proteins are known.

Investigation of the mechanism for penetration of low density lipoprotein into the arterial wall

NASA Astrophysics Data System (ADS)

Glukhova, O. E.; Zyktin, A. A.; Slepchenkov, M. M.

2018-02-01

Currently, the pathology of the cardiovascular system is an extremely urgent problem of fundamental and clinical medicine. These diseases are caused, mainly, by atherosclerotic changes in the wall of blood vessels. The predominant role in the development of atherosclerosis is attributed to the penetration of various kinds of lipoproteins into the arterial intima. In this paper, we in silico investigated the dynamics of the penetration of low density lipoprotein (LDL) through the intercellular gap using molecular modeling methods. The simulation was carried out in the GROMACS software package using a coarse-grained MARTINI model. During investigation we carried out the LDL self-assembly for the first time. The coarse-grained model of LDL was collected from the following molecules: POPC (phosphatidylcholine) - 630 molecules, LPC (lysophosphatidylcholine) - 80 molecules CHOL (cholesterol) - 600 molecules CHYO (cholesteryl oleate) - 1600 molecules TOG (glycerol trioleate) 180 Molecules. The coarse-grained model of the intercellular endothelial gap was based on a model of lipid bilayer consisting of DPPC phospholipids and cholesterol in a percentage ratio of 70% and 30%, respectively. Based on the obtained results, we can predict the mechanism of LDL diffusion. Lipoproteins can be deformed so as to pass through narrow gaps. Our investigations open the way for the research of the behavior dynamics of LDL moving with the blood flow rate when interacting with the intercellular gaps of the endothelial layer of the vessel inner wall.

Chromatographic analysis of lipid fractions in healthy dogs and dogs with obesity or hyperadrenocorticism.

PubMed

Jericó, Márcia Marques; De Camargo Chiquito, Fernanda; Kajihara, Kazuo; Moreira, Márcio Antonio Bastistela; Gonzales, Rodrigo; Machado, Fabricio Lorenzini Aranha; Nunes, Valéria Sutti; Catanozi, Sergio; Nakandakare, Edna Regina

2009-03-01

Obesity and endogenous hyperadrenocorticism (HAC) are common clinical conditions in veterinary practice, and both conditions have clinical and laboratory similarities, such as weight gain and dyslipidemia. The objective of the present study was to characterize and compare the lipid profiles and plasma lipoprotein fractions in healthy dogs (n = 10), in obese dogs (n = 10), and in dogs with HAC (n = 6). All of the dogs were client owned. The lipoproteins were separated by fast protein liquid chromatography, and the plasma concentrations of total cholesterol and total triacylglycerol (TAG) were determined by enzymatic methods. When compared with the healthy and obese groups, dogs with HAC had a significant increase (P < 0.01) in the total concentrations of TAGs and cholesterol (CHOL), with higher distribution in the very low-density lipoprotein (VLDL)-CHOL fractions. In addition, the distributions of the high-density lipoprotein (HDL)-CHOL and HDL-TAG fractions were significantly lower (P < 0.01) in dogs with HAC than in healthy dogs. Considering the animals in this study, it was determined that the dogs with HAC differed significantly from the healthy and obese dogs regarding the metabolism of CHOL and TAG, as well as their VLDL and HDL fractions. Similar laboratory findings could allow veterinarians to distinguish obese dogs from those with HAC. In addition, dogs with HAC may be at higher risk for developing metabolic and atherosclerotic complications.

Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids

PubMed Central

Teslovich, Tanya M.; Musunuru, Kiran; Smith, Albert V.; Edmondson, Andrew C.; Stylianou, Ioannis M.; Koseki, Masahiro; Pirruccello, James P.; Ripatti, Samuli; Chasman, Daniel I.; Willer, Cristen J.; Johansen, Christopher T.; Fouchier, Sigrid W.; Isaacs, Aaron; Peloso, Gina M.; Barbalic, Maja; Ricketts, Sally L.; Bis, Joshua C.; Aulchenko, Yurii S.; Thorleifsson, Gudmar; Feitosa, Mary F.; Chambers, John; Orho-Melander, Marju; Melander, Olle; Johnson, Toby; Li, Xiaohui; Guo, Xiuqing; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C.; Lange, Leslie A.; Smith, Joshua D.; Song, Kijoung; Zhao, Jing Hua; Yuan, Xin; Luan, Jian'an; Lamina, Claudia; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y.L.; Wright, Alan F.; Witteman, Jacqueline C.M.; Wilson, James F.; Willemsen, Gonneke; Wichmann, H-Erich; Whitfield, John B.; Waterworth, Dawn M.; Wareham, Nicholas J.; Waeber, Gérard; Vollenweider, Peter; Voight, Benjamin F.; Vitart, Veronique; Uitterlinden, Andre G.; Uda, Manuela; Tuomilehto, Jaakko; Thompson, John R.; Tanaka, Toshiko; Surakka, Ida; Stringham, Heather M.; Spector, Tim D.; Soranzo, Nicole; Smit, Johannes H.; Sinisalo, Juha; Silander, Kaisa; Sijbrands, Eric J.G.; Scuteri, Angelo; Scott, James; Schlessinger, David; Sanna, Serena; Salomaa, Veikko; Saharinen, Juha; Sabatti, Chiara; Ruokonen, Aimo; Rudan, Igor; Rose, Lynda M.; Roberts, Robert; Rieder, Mark; Psaty, Bruce M.; Pramstaller, Peter P.; Pichler, Irene; Perola, Markus; Penninx, Brenda W.J.H.; Pedersen, Nancy L.; Pattaro, Cristian; Parker, Alex N.; Pare, Guillaume; Oostra, Ben A.; O'Donnell, Christopher J.; Nieminen, Markku S.; Nickerson, Deborah A.; Montgomery, Grant W.; Meitinger, Thomas; McPherson, Ruth; McCarthy, Mark I.; McArdle, Wendy; Masson, David; Martin, Nicholas G.; Marroni, Fabio; Mangino, Massimo; Magnusson, Patrik K.E.; Lucas, Gavin; Luben, Robert; Loos, Ruth J. F.; Lokki, Maisa; Lettre, Guillaume; Langenberg, Claudia; Launer, Lenore J.; Lakatta, Edward G.; Laaksonen, Reijo; Kyvik, Kirsten O.; Kronenberg, Florian; König, Inke R.; Khaw, Kay-Tee; Kaprio, Jaakko; Kaplan, Lee M.; Johansson, Åsa; Jarvelin, Marjo-Riitta; Janssens, A. Cecile J.W.; Ingelsson, Erik; Igl, Wilmar; Hovingh, G. Kees; Hottenga, Jouke-Jan; Hofman, Albert; Hicks, Andrew A.; Hengstenberg, Christian; Heid, Iris M.; Hayward, Caroline; Havulinna, Aki S.; Hastie, Nicholas D.; Harris, Tamara B.; Haritunians, Talin; Hall, Alistair S.; Gyllensten, Ulf; Guiducci, Candace; Groop, Leif C.; Gonzalez, Elena; Gieger, Christian; Freimer, Nelson B.; Ferrucci, Luigi; Erdmann, Jeanette; Elliott, Paul; Ejebe, Kenechi G.; Döring, Angela; Dominiczak, Anna F.; Demissie, Serkalem; Deloukas, Panagiotis; de Geus, Eco J.C.; de Faire, Ulf; Crawford, Gabriel; Collins, Francis S.; Chen, Yii-der I.; Caulfield, Mark J.; Campbell, Harry; Burtt, Noel P.; Bonnycastle, Lori L.; Boomsma, Dorret I.; Boekholdt, S. Matthijs; Bergman, Richard N.; Barroso, Inês; Bandinelli, Stefania; Ballantyne, Christie M.; Assimes, Themistocles L.; Quertermous, Thomas; Altshuler, David; Seielstad, Mark; Wong, Tien Y.; Tai, E-Shyong; Feranil, Alan B.; Kuzawa, Christopher W.; Adair, Linda S.; Taylor, Herman A.; Borecki, Ingrid B.; Gabriel, Stacey B.; Wilson, James G.; Stefansson, Kari; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Krauss, Ronald M.; Mohlke, Karen L.; Ordovas, Jose M.; Munroe, Patricia B.; Kooner, Jaspal S.; Tall, Alan R.; Hegele, Robert A.; Kastelein, John J.P.; Schadt, Eric E.; Rotter, Jerome I.; Boerwinkle, Eric; Strachan, David P.; Mooser, Vincent; Holm, Hilma; Reilly, Muredach P.; Samani, Nilesh J; Schunkert, Heribert; Cupples, L. Adrienne; Sandhu, Manjinder S.; Ridker, Paul M; Rader, Daniel J.; van Duijn, Cornelia M.; Peltonen, Leena; Abecasis, Gonçalo R.; Boehnke, Michael; Kathiresan, Sekar

2010-01-01

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. PMID:20686565

Impact of Dietary Calcium Supplement on Circulating Lipoprotein Concentrations and Atherogenic Indices in Overweight and Obese Individuals: A Systematic Review.

PubMed

Heshmati, Javad; Sepidarkish, Mahdi; Namazi, Nazli; Shokri, Fatemeh; Yavari, Mahsa; Fazelian, Siavash; Khorshidi, Masoud; Shidfar, Farzad

2018-03-21

Dyslipidemia is the main risk factor for developing cardiovascular disease. There are discrepancies in the effects of calcium supplementation on modulation of lipid status. Therefore, we aimed to summarize the effects of dietary calcium supplement on circulating lipoprotein concentrations and atherogenic indices in overweight and obese individuals. We conducted a systematic literature search from 2000 until July 2016. PubMed, Scopus, Cochran Library, and ISI Web of Science databases were searched for clinical trials written in English. Placebo controlled clinical trials on calcium or calcium with vitamin D supplement in overweight and obese indiciduals were considered. Finally, 11 clinical trials met the criteria and were included. Most studies (n = 9) evaluated Ca/D co-supplementation. Positive effects of calcium supplementation alone or with vitamin D were as follows: serum levels of total cholesterol (TC; n = 1), triglyceride (TG) concentrations (n = 1), serum levels of low-density lipoprotein cholesterol (LDL-C; n = 5) and high-density lipoprotein cholesterol (HDL-C; n = 3). Seven clinical trials reported atherogenic indices and three of them demonstrated beneficial effects of calcium supplementation on at least one atherogenic index. Calcium supplementation may not be helpful to reduce serum levels of TC and TG in overweight and obese individuals. However, it may modulate LDL-C and HDL-C concentration. More studies are warranted to clarify the effects of calcium supplementation on each atherogenic index.

PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

NASA Astrophysics Data System (ADS)

Wang, Ling; Wang, Yu; Liang, Yong; Li, Jia; Liu, Yuchen; Zhang, Jie; Zhang, Aiqian; Fu, Jianjie; Jiang, Guibin

2014-04-01

Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.

Relation of fish oil supplementation to markers of atherothrombotic risk in patients with cardiovascular disease not receiving lipid-lowering therapy.

PubMed

Franzese, Christopher J; Bliden, Kevin P; Gesheff, Martin G; Pandya, Shachi; Guyer, Kirk E; Singla, Anand; Tantry, Udaya S; Toth, Peter P; Gurbel, Paul A

2015-05-01

Fish oil supplementation (FOS) is known to have cardiovascular benefits. However, the effects of FOS on thrombosis are incompletely understood. We sought to determine if the use of FOS is associated with lower indices of atherothrombotic risk in patients with suspected coronary artery disease (sCAD). This is a subgroup analysis of consecutive patients with sCAD (n=600) enrolled in the Multi-Analyte, Thrombogenic, and Genetic Markers of Atherosclerosis study. Patients on FOS were compared with patients not on FOS. Lipid profile was determined by vertical density gradient ultracentrifugation (n=520), eicosapentaenoic acid+docosahexaenoic acid was measured by gas chromatography (n=437), and AtherOx testing was performed by immunoassay (n=343). Thromboelastography (n=419), ADP- and collagen-induced platelet aggregation (n=137), and urinary 11-dehydrothromboxane B2 levels (n=259) were performed immediately before elective coronary angiography. In the total population, FOS was associated with higher eicosapentaenoic acid+docosahexaenoic acid content (p<0.001), lower triglycerides (p=0.04), total very low-density lipoprotein cholesterol (p=0.002), intermediate-density lipoprotein cholesterol (p=0.02), and AtherOx levels (p=0.02) but not in patients on lipid-lowering therapy. Patients not on lipid-lowering therapy taking FOS had lower very low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, remnant lipoproteins, triglycerides, low-density lipoprotein cholesterol, AtherOx levels, collagen-induced platelet aggregation, thrombin-induced platelet-fibrin clot strength, and shear elasticity (p<0.03 for all). In clopidogrel-treated patients, there was no difference in ADP-induced aggregation between FOS groups. Patients on FOS had lower urinary 11-dehydrothromboxane B2 levels regardless of lipid-lowering therapy (p<0.04). In conclusion, the findings of this study support the potential benefit of FOS for atherothrombotic risk reduction in sCAD with the greatest benefit in patients not receiving lipid-lowering therapy. Future prospective studies to compare FOS with lipid-lowering therapy and to assess the independent effects of FOS on thrombogenicity are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Newer antiatherosclerosis treatment strategies.

PubMed

Aggarwal, Amitesh; Singh, Safal

2011-01-01

Atherosclerosis has been a target of much clinical and molecular research. As a result of this extensive research, it is amply clear that atherogenesis is a multifactorial process involving an interplay of metabolic, immune and inflammatory mechanisms. Antiatherosclerotic strategies are today aiming for a multipronged approach targeting each arm of this multifactorial process. The newer agents under development can be divided into three broad categories: anti-inflammatory agents, modulators of intermediary metabolism and antiatherosclerosis vaccines. Potential targets for anti-inflammatory agents include inhibition of conversion of low-density lipoprotein (LDL) to oxidised LDL, blocking or downregulation of cell adhesion molecules, chemokine modulation and macrophage receptor blockade. Beyond inhibition of plaque formation, efforts are also ongoing to develop agents which stabilise the plaque by increasing its fibrous content and inhibiting its disruption. So far as research in the sphere of intermediary metabolism is concerned, the focus is now primarily on raising high-density lipoprotein and promoting reverse cholesterol transport; potential targets include cholesteryl ester transfer protein, liver X-receptor, lecithin cholesterol acyltransferase and high-density lipoprotein mimetics. Acyl-coenzymeA: cholesterol acyltransferase is another enzyme whose selective and differential inhibition is under active investigation. The concept of immunisation against a non-communicable disease such as atherosclerosis is still in its nascent stages. However, with increasing evidence to suggest the role of antigen-specific T-cell-mediated immunity in atherogenesis, this approach is potentially promising. Possible antigens under evaluation include oxidised LDL and its subparticles, heat-shock proteins and cholesteryl ester transfer protein. With cardiovascular disease being the single leading cause of death worldwide, the development of a safe and successful antiatherosclerosis strategy (possibly employing a combination of agents acting at various levels) will indeed be a major 21st-century achievement.

Titration of Serum Lipoproteins with Lipoprotein Precipitants.

DTIC Science & Technology

1981-12-01

Lipid Res 11:583 (1970). 6. Grove, T. H. Effect of reagent pH on determination of high-density lipo- protein cholesterol by precipitation with sodium ...of choles- terol in the supernate plateaued at 43 mg/dl after the beta and prebeta lipo- proteins had been precipitated . The intensities of the two...AD-A113 370 SCHOOL OF AEROSPACE MEDICINE BROOKS AFS TX F/S 6/1 TITRATION OF SERU’LIPOPROTEINS WITH LIPOPROTEIN PRECIPITANTS .(Ul DEC 81 0 A CLARK. J A

The small dense LDL particle/large buoyant LDL particle ratio is associated with glucose metabolic status in pregnancy.

PubMed

Chen, Yanmin; Du, Mengkai; Xu, Jianyun; Chen, Danqing

2017-12-14

The lipoprotein subfraction particle profile can be used to improve clinical assessments of cardiovascular disease risk and contribute to early detection of atherogenic dyslipidemia. Lipid alterations in gestational diabetes have been extensively studied, but the results have been inconsistent. Here, we investigated serum lipoprotein subfraction particle levels and their association with glucose metabolic status in pregnancy. Twenty-eight pregnant women with gestational diabetes and 56 pregnant women with normal glucose tolerance matched for body mass index were enrolled in this study. We assessed fasting serum lipid concentrations and lipoprotein subfraction particle levels in participants between 24 and 28 weeks of gestation. The level of low-density lipoprotein (LDL) cholesterol was significantly lower in women with gestational diabetes than in those with normal glucose tolerance, but the triglyceride and high-density lipoprotein (HDL) cholesterol levels of the two groups were similar. Lipoprotein particle analysis showed that very-low-density lipoprotein (VLDL) particle number and the small dense LDL particle/large buoyant LDL particle (sdLDL-P/lbLDL-P) ratio were significantly higher in women with gestational diabetes than in those with normal glucose tolerance (P = 0.013 and P = 0.015, respectively). In multivariate analysis, fasting glucose was independently and positively associated with sdLDL-P/lbLDL-P ratio even after adjustment for maternal age, gestational weight gain, BMI and LDL cholesterol (standardized Beta = 0.214, P = 0.029). The sdLDL-P/lbLDL-P ratio is higher in GDM compared with non-diabetic pregnant women, and positively and independently associated with fasting glucose in pregnant women.

Effect of relative weight group change on nuclear magnetic resonance spectroscopy derived lipoprotein particle size and concentrations among adolescents.

PubMed

Jago, Russell; Drews, Kimberly L; Otvos, James D; Foster, Gary D; Marcus, Marsha D; Buse, John B; Mietus-Snyder, Michele; Willi, Steven M

2014-05-01

To examine whether longitudinal changes in relative weight category (as indicated by change in body mass index [BMI] classification group) were associated with changes in nuclear magnetic resonance (NMR)-derived lipoprotein particles among US youth. Secondary analysis of data from a clustered randomized controlled trial. BMI and fasting blood samples were obtained from 2069 participants at the start of the 6th grade and end of the 8th grade. BMI was categorized as normal weight, overweight, or obese at both time points. Lipoprotein particle profiles were measured with NMR spectroscopy at both time points. Regression models were used to examine changes in relative weight group and change in lipoprotein variables. A total of 38% of participants changed relative weight category (BMI group) during the 2.5-year study period. Low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (HDL) cholesterol decreased almost universally, but more with improved BMI category. There were adverse effects on LDL size and total LDL particles, HDL size, and cholesterol for participants who remained obese or whose relative weight group worsened. Changes in relative category had no impact on HDL particles. Improvement in relative weight group from 6th to 8th grade was associated with favorable changes in non-HDL cholesterol, very low-density lipoprotein size, LDL size, HDL size, and LDL particles but had no effect on HDL particles. Findings indicate that an improvement in relative weight group between 6th and 8th grade had an effect on NMR-derived particles sizes and concentrations among a large group of adolescents, which overrepresented low-income minorities. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between insulin resistance-associated metabolic parameters and anthropometric measurements with sugar-sweetened beverage intake and physical activity levels in US adolescents: findings from the 1999-2004 National Health and Nutrition Examination Survey.

PubMed

Bremer, Andrew A; Auinger, Peggy; Byrd, Robert S

2009-04-01

To evaluate the relationship between insulin resistance-associated metabolic parameters and anthropometric measurements with sugar-sweetened beverage intake and physical activity levels. A cross-sectional analysis of the National Health and Nutrition Examination Survey data collected by the National Center for Health Statistics. Nationally representative samples of US adolescents participating in the National Health and Nutrition Examination Survey during the years 1999-2004. A total of 6967 adolescents aged 12 to 19 years. Sugar-sweetened beverage consumption and physical activity levels. Glucose and insulin concentrations, a homeostasis model assessment of insulin resistance (HOMA-IR), total, high-density lipoprotein, and low-density lipoprotein cholesterol concentrations, triglyceride concentrations, systolic and diastolic blood pressure, waist circumference, and body mass index (calculated as weight in kilograms divided by height in meters squared) percentile for age and sex. Multivariate linear regression analyses showed that increased sugar-sweetened beverage intake was independently associated with increased HOMA-IR, systolic blood pressure, waist circumference, and body mass index percentile for age and sex and decreased HDL cholesterol concentrations; alternatively, increased physical activity levels were independently associated with decreased HOMA-IR, low-density lipoprotein cholesterol concentrations, and triglyceride concentrations and increased high-density lipoprotein cholesterol concentrations. Furthermore, low sugar-sweetened beverage intake and high physical activity levels appear to modify each others' effects of decreasing HOMA-IR and triglyceride concentrations and increasing high-density lipoprotein cholesterol concentrations. Sugar-sweetened beverage intake and physical activity levels are each independently associated with insulin resistance-associated metabolic parameters and anthropometric measurements in adolescents. Moreover, low sugar-sweetened beverage intake and high physical activity levels appear to modify each others' effects on several health-related outcome variables.

Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

PubMed

Huang, Rong; Zheng, Jun; Li, Shengxian; Tao, Tao; Ma, Jing; Liu, Wei

2015-05-01

To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. A cross-sectional study. Medical university hospital. A total of 229 women with polycystic ovary syndrome aged 18-45 years. Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p < 0.05); women with phenotype 4 (oligo/anovulation and polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing factor for insulin resistance and for the aggravation of other metabolic profiles. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

The relationship between insulin resistance and periodontitis is not affected by Mediterranean diet in a Spanish population.

PubMed

Pulido-Moran, M; Bullon, P; Morillo, J M; Battino, M; Quiles, J L; Ramirez-Tortosa, MCarmen

2017-05-01

To examine the insulin resistance measured by surrogate indices in subjects with and without periodontitis and to find out any correlation among dietary intake with insulin resistance. Fifty-five patients were recruited to participate in this cross-sectional study. Insulin resistance measured by the homoeostasis model assessment (HOMA-IR) and the quantitative insulin sensitivity check index moreover glycaemia, creatinine, uric acid, high density lipoproteins, low density lipoproteins, very low density lipoproteins and triglycerides among others. True periodontal disease was elucidated through the examination of probing pocket depth, clinical attachment level, recession of the gingival margin and gingival bleeding. The statistical analyses used were the student's T-test for independent variables, Kolmogorov-Smirnov if variations were homogeneous; if not, the Mann-Whitney U Test was applied instead. Correlations between variables were assessed using Pearson's correlation coefficients. True periodontal disease was confirmed through the greater values of probing pocket depth, clinical attachment level, gingival margin and gingival bleeding in the periodontitis group in comparison with non-periodontitis group. Insulin resistance was evidenced by the greater values of HOMA-IR as well as by the lower quantitative insulin sensitivity check index values in the periodontitis group. Fasting insulin, glucose, uric acid, creatinine, low density lipoproteins, triglycerides and very low density lipoprotein levels were significant higher in periodontitis group. Pearson's correlations did not show any association among diet data and insulin resistance parameters in periodontitis patients. A putative systemic relationship between insulin resistance and periodontitis exists but it does not seem conceivable any effect of diet over such relationship. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH).

PubMed

2011-03-01

The aim of this study was to test the hypothesis that patients with atherosclerotic cardiovascular (CV) disease optimally treated on a statin but with residual atherogenic dyslipidemia (low high-density lipoprotein cholesterol [HDL-C] and high triglycerides) will benefit from addition of niacin with fewer CV events compared with placebo. Statin monotherapy trials have found 25%-35% CV risk reduction relative to placebo, leaving significant residual risk. Patients with atherogenic dyslipidemia have substantially increased CV risk. Participants were men and women with established CV disease and atherogenic dyslipidemia. Lipid entry criteria varied by gender and statin dose at screening. All participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain low-density lipoprotein cholesterol (LDL-C) 40-80 mg/dL (1.03-2.07 mmol/L). Participants were randomized to extended-release niacin or matching placebo. The primary end point was time to occurrence of the first of the following: coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. This event-driven trial will have 85% power to show a 25% reduction in primary event frequency after 850 patients have experienced a primary outcome event. AIM-HIGH completed enrollment in April 2010. Follow-up is expected to continue through 2012. AIM-HIGH was designed to determine whether treating residual dyslipidemia with niacin further reduces cardiovascular events in patients with CV disease on a statin at target levels of low-density lipoprotein cholesterol. Copyright © 2011 Mosby, Inc. All rights reserved.

Regulation of lecithin-cholesterol acyltransferase reaction by acyl acceptors and demonstration of its "idling" reaction.

PubMed

Czarnecka, H; Yokoyama, S

1993-09-15

The mechanism for regulation of cholesterol esterification by lecithin-cholesterol acyltransferase (LCAT) was studied using the highly isolated enzyme from pig plasma. In the reaction with phosphatidylcholine small unilamellar vesicles, cholesterol, water, diacylglycerol, and lysophosphatidylcholine were all potent acceptors of an acyl group cleaved from the sn-2 position of egg phosphatidylcholine, generating cholesteryl ester, free fatty acid, triglyceride, and phosphatidylcholine, respectively. All of these reactions required activation by human apolipoprotein A-I, suggesting that this activation leads to the deacylation of phosphatidylcholine. Those acceptors competed against each other in this vesicle reaction system, and cholesterol was the most potent acyl acceptor. Lysophosphatidylcholine that was endogenously generated by deacylation of phosphatidylcholine in the first step of the LCAT reaction was also a good acyl acceptor, showing that the reaction is always partly "idling." Bovine serum albumin partially inhibited this idling reaction in a concentration-dependent manner up to 80% at 0.60 mM. The above results were essentially reproducible with high density lipoprotein, except that cholesterol is less potent than lysophosphatidylcholine in accepting the acyl group under the condition used. Unlike the apolipoprotein A-I-activated reaction, cholesterol was esterified only slightly by the LCAT reaction on low density lipoprotein and, consequently, did not compete against lysophosphatidylcholine for generation of phosphatidylcholine. Thus, apoB may activate LCAT in a very different manner from apoA-I. The rate of esterification of lysophosphatidylcholine on low density lipoprotein was one-tenth of that on the vesicles and on high density lipoprotein. Thus, LCAT is active on low density lipoprotein but mostly idling as deacylating and reacylating glycerophospholipids.

Association of socioeconomic stratification with plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children

PubMed Central

Bosch, Virgilio; Giacopini, Maria Isabel

2016-01-01

Abstract Objetive: To establish association between socioeconomic status and plasmatic markers of lipoperoxidation and antioxidants in Venezuelan school-age children from the middle-class and in critical poverty. Methods: Cross-sectional study with a sample of 114 school-age children (aged 7-9). The socioeconomic status, dietary intake of macro and micro-nutrients, weight, height, lipid profile, indicators of lipid peroxidation and enzymatic and non-enzymatic antioxidants were determined. Results: The daily average intake of energy, carbohydrates and vitamin A, and the percentage of energy obtained from carbohydrates was significantly higher in middle-class children compared to critical poverty children (p <0.05). The circulating oxidized low density lipoprotein (p <0.001) and the susceptibility of low density lipoproteins and very low density lipoproteins to oxidation in vitro (p <0.05) were significantly higher in middle-class children, while the critical poverty children showed significantly lower levels of Vitamin C and E in plasma (p <0.05). Non-enzymatic antioxidant levels were frequently deficient in both strata. The concentrations of circulating oxidized low density lipoprotein (OR: 1.09, CI 95%: 1.016-1.179; p= 0.017) and Vitamin C (OR: 3.21, CI 95%: 1.104-9.938; p= 0.032) were associated to the socioeconomic status independently of gender, family history of premature coronary artery disease, triglicerides, Vitamin C and E dietary intake and count of white blood cells. Conclusion: The socioeconomic status was associated to circulating oxidized low density lipoprotein and Vitamin C in Venezuelan school-age children, The results suggested the need to improve the dietary intake of antioxidants in both studied socioeconomic groups. PMID:28293041

Appraisal of Antihyperlipidemic Activities of Lentinus lepideus in Hypercholesterolemic Rats

PubMed Central

Yoon, Ki Nam; Lee, Jae Seong; Kim, Hye Young; Lee, Kyung Rim; Shin, Pyung Gyun; Cheong, Jong Chun; Yoo, Young Bok; Alam, Nuhu; Ha, Tai Moon

2011-01-01

The wild edible mushroom, Lentinus lepideus has recently been cultivated for commercial use in Korea. While the mushroom has been widely used for nutritional and medicinal purposes, the possible anti-hyperlipidemic action is unclear. The effects of dietary L. lepideus on plasma and feces biochemical and on the liver histological status were investigated in hypercholesterolemic rats. Six-wk-old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Biochemical and histological examinations were performed. A diet containing 5% L. lepideus fruiting bodies reduced plasma total cholesterol, triglyceride, low-density lipoprotein, total lipid, phospholipids, and the ratio of low-density to high-density lipoprotein. Body weight was reduced. The diet did not adversely affect plasma biochemical and enzyme profiles. L. lepideus reduced significantly plasma β- and pre-β-lipoprotein, while α-lipoprotein content was increased. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red O staining revealed normal findings for mushroom-fed hypercholesterolemic rats. The present study suggests that a diet supplemented with L. lepideus can provide health benefits by acting on the atherogenic lipid profile in hypercholesterolemic rats. PMID:22783117

Inhibition of low-density lipoprotein oxidation and up-regulation of low-density lipoprotein receptor in HepG2 cells by tropical plant extracts.

PubMed

Salleh, Mohd Nizar; Runnie, Irine; Roach, Paul D; Mohamed, Suhaila; Abeywardena, Mahinda Y

2002-06-19

Twelve edible plant extracts rich in polyphenols were screened for their potential to inhibit oxidation of low-density lipoprotein (LDL) in vitro and to modulate LDL receptor (LDLr) activity in cultured HepG2 cells. The antioxidant activity (inhibition of LDL oxidation) was determined by measuring the formation of conjugated dienes (lag time) and thiobarbituric acid reagent substances (TBARS). Betel leaf (94%), cashew shoot (63%), Japanese mint (52%), semambu leaf (50%), palm frond (41%), sweet potato shoot, chilli fruit, papaya shoot, roselle calyx, and maman showed significantly increased lag time (>55 min, P < 0.05) and inhibition of TBARS formation (P < 0.05) compared to control. LDLr was significantly up-regulated (P < 0.05) by Japanese mint (67%), semambu (51%), cashew (50%), and noni (49%). Except for noni and betel leaf, most plant extracts studied demonstrated a positive association between antioxidant activity and the ability to up-regulate LDL receptor. Findings suggest that reported protective actions of plant polyphenols on lipoprotein metabolism might be exerted at different biochemical mechanisms.

Inhibition of triacylglycerol and apoprotein B secretion and of low density lipoprotein binding in Hep G2 cells by eicosapentaenoic acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, S.H.; Nestel, P.J.

1987-05-01

The consumption of long chain polyunsaturated fatty acids of fish oils leads to profound lowering of plasma triacylglyercol (TAG) but not of plasma cholesterol. Reasons for this were investigated with the human hepatoma cell line, the Hep G2 cell. Incubations with oleic acid (OA), linoleic acid (LA) and the characteristic marine fatty acid eicosapentaenoic acid (EPA) enriched cellular TAG mass, though least with EPA. However, secretion of very low density lipoprotein (VLDL)-TAG and apoprotein B (apo B), measured from (/sup 3/H)-glycerol and (/sup 3/H)-leucine was markedly inhibited by EPA. Preincubation with LA reduced VLDL-TAG but not apo B secretion inmore » comparison with OA which stimulated both. A possible effect on low density lipoprotein (LDL) removal was studied by measuring (/sup 125/I)-LDL binding. Preincubation with either EPA or LA inhibited the saturable binding of LDL, observed with OA and control incubations. The binding of lipoproteins containing chylomicron remnants was not affected by any of the fatty acids.« less

ApoE and the role of very low density lipoproteins in adipose tissue inflammation

USDA-ARS?s Scientific Manuscript database

Our goal was too identify the role of triglyceride-rich lipoproteins and apoE, a major apolipoprotein in triglyceride-rich lipoproteins, in adipose tissue inflammation with high-fat diet induced obesity. Male apoE-/- and C57BL/6J wild-type mice fed high fat diets for 12 weeks were assessed for metab...

Nanotechnology for Synthetic High Density Lipoproteins

PubMed Central

Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad

2014-01-01

Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901

Total saponins from Rosa laevigata Michx fruit attenuates hepatic steatosis induced by high-fat diet in rats.

PubMed

Dong, Deshi; Qi, Yan; Xu, Lina; Yin, Lianhong; Xu, Youwei; Han, Xu; Zhao, Yanyan; Peng, Jinyong

2014-12-01

The protective effects of total saponins from Rosa laevigata Michx fruit (RLTS) in high-fat diet (HFD)-induced rats were investigated. The results showed that oral administration of RLTS attenuated hepatic steatosis, significantly reduced the levels of body weight, alanine transaminase, aspartate transaminase, total cholesterol, total triglyceride, free fatty acids, low density lipoprotein, blood glucose, insulin and malondialdehyde, and increased high density lipoprotein and glutathione levels compared with the model group. Further investigations showed that RLTS affected fatty acid synthesis, fatty acid β-oxidation, fatty acid ω-oxidation, total cholesterol and triglyceride metabolism and synthesis. Moreover, the extract obviously suppressed HFD-induced oxidative stress and inflammation. These results suggest that RLTS should be developed to be one functional food or health product against non-alcoholic fatty liver disease (NAFLD) in the future.

Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

USDA-ARS?s Scientific Manuscript database

Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

Association of metabolic syndromes and risk factors with ampullary tumors development: a case-control study in China.

PubMed

He, Xiao-Dong; Wu, Qiao; Liu, Wei; Hong, Tao; Li, Jing-Jing; Miao, Ruo-Yu; Zhao, Hai-Tao

2014-07-28

To evaluate the risk factors for ampullary adenoma and ampullary cancer. This case-control study included ampullary tumor patients referred to Peking Union Medical College Hospital. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of the same hospital. Data on metabolic syndromes, medical conditions, and family history were collected by retrospective review of the patients' records and health examination reports, or by interview. A total of 181 patients and 905 age- and sex-matched controls were enrolled. We found that a history of diabetes, cholecystolithiasis, low-density lipoprotein, and apolipoprotein A were significantly related to ampullary adenomas. Diabetes, cholecystolithiasis, chronic pancreatitis, total cholesterol, high-density lipoprotein, and apolipoprotein A were also significantly related to ampullary cancer. Some metabolic syndrome components and medical conditions are potential risk factors for the development of ampullary tumors. Cholelithiasis, diabetes, and apolipoprotein A may contribute to the malignant transformation of benign ampullary adenomas into ampullary cancer.

A chimeric peptide of intestinal trefoil factor containing cholesteryl ester transfer protein B cell epitope significantly inhibits atherosclerosis in rabbits after oral administration.

PubMed

Qi, Gaofu; Li, Jingjing; Wang, Shengying; Xin, Shanshan; Du, Peng; Zhang, Qingye; Zhao, Xiuyun

2011-04-01

Vaccination against cholesteryl ester transfer protein (CETP) is proven to be effective for inhibiting atherosclerosis in animal models. In this study, the proteases-resistant intestinal trefoil factor (TFF3) was used as a molecular vehicle to construct chimeric TFF3 (cTFF3) containing CETP B cell epitope and tetanus toxin helper T cell epitope. It was found that cTFF3 still preserved a trefoil structure, and can resist proteases digestion in vitro. After oral immunization with cTFF3, the CETP-specific IgA and IgG could be found in intestine lavage fluid and serum, and the anti-CETP antibodies could inhibit partial CETP activity to increase high-density lipoprotein cholesterol, decrease low-density lipoprotein cholesterol, and inhibit atherosclerosis in animals. Therefore, TFF3 is a potential molecular vehicle for developing oral peptide vaccines. Our research highlights a novel strategy for developing oral peptide vaccines in the future. Copyright © 2010 Elsevier Inc. All rights reserved.

Dietary fatty acids were not independently associated with lipoprotein subclasses in elderly women.

PubMed

Alaghehband, Fatemeh Ramezan; Lankinen, Maria; Värri, Miika; Sirola, Joonas; Kröger, Heikki; Erkkilä, Arja T

2017-07-01

Dietary fatty acids are known to affect serum lipoproteins; however, little is known about the associations between consumption of dietary fatty acids and lipoprotein subclasses. In this study, we hypothesized that there is an association between dietary fatty acids and lipoprotein subclasses and investigated the cross-sectional association of dietary fat intake with subclasses of lipoproteins in elderly women. Altogether, 547 women (aged ≥65 years) who were part of OSTPRE cohort participated. Dietary intake was assessed by 3-day food records, lifestyle, and health information obtained through self-administrated questionnaires, and lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. To analyze the associations between fatty acids and lipoprotein subclasses, we used Pearson and Spearman correlation coefficients and the analysis of covariance (ANCOVA) test with, adjustment for physical activity, body mass index, age, smoking status, and intake of lipid-lowering drugs. There were significant correlations between saturated fatty acids (SFA; % of energy) and concentrations of large, medium, and small low-density lipoproteins (LDL); total cholesterol in large, medium, and small LDL; and phospholipids in large, medium, and small LDL, after correction for multiple testing. After adjustment for covariates, the higher intake of SFA was associated with smaller size of LDL particles (P = .04, ANCOVA) and lower amount of triglycerides in small very low-density lipoproteins (P = .046, ANCOVA). However, these associations did not remain significant after correction for multiple testing. In conclusion, high intake of SFA may be associated with the size of LDL particles, but the results do not support significant, independent associations between dietary fatty acids and lipoprotein subclasses. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development

PubMed Central

Nagoor Meeran, Mohamed Fizur; Javed, Hayate; Al Taee, Hasan; Azimullah, Sheikh; Ojha, Shreesh K.

2017-01-01

Thymol, chemically known as 2-isopropyl-5-methylphenol is a colorless crystalline monoterpene phenol. It is one of the most important dietary constituents in thyme species. For centuries, it has been used in traditional medicine and has been shown to possess various pharmacological properties including antioxidant, free radical scavenging, anti-inflammatory, analgesic, antispasmodic, antibacterial, antifungal, antiseptic and antitumor activities. The present article presents a detailed review of the scientific literature which reveals the pharmacological properties of thymol and its multiple therapeutic actions against various cardiovascular, neurological, rheumatological, gastrointestinal, metabolic and malignant diseases at both biochemical and molecular levels. The noteworthy effects of thymol are largely attributed to its anti-inflammatory (via inhibiting recruitment of cytokines and chemokines), antioxidant (via scavenging of free radicals, enhancing the endogenous enzymatic and non-enzymatic antioxidants and chelation of metal ions), antihyperlipidemic (via increasing the levels of high density lipoprotein cholesterol and decreasing the levels of low density lipoprotein cholesterol and low density lipoprotein cholesterol in the circulation and membrane stabilization) (via maintaining ionic homeostasis) effects. This review presents an overview of the current in vitro and in vivo data supporting thymol’s therapeutic activity and the challenges concerning its use for prevention and its therapeutic value as a dietary supplement or as a pharmacological agent or as an adjuvant along with current therapeutic agents for the treatment of various diseases. It is one of the potential candidates of natural origin that has shown promising therapeutic potential, pharmacological properties and molecular mechanisms as well as pharmacokinetic properties for the pharmaceutical development of thymol. PMID:28694777

[The high content of palmitinic fatty acid in food as a major cause of increase of concentration of cholesterol and low density lipoproteins and atheromatous plaques of arteries' intima].

PubMed

Titov, V N

2013-02-01

The positioning of individual triglycerides of blood serum in palmitinic and oleic lipoproteins ofvery low density in the order ofincrease of the rate constant of their hydrolysis under action of post-heparin lipoprotein leads to the sequence as follows: palmitoil-palmitoil-palmitate-->palmitoil-palmitoil-oleate-->palmitoil-oleil-palmitat-->oleil-palmitoil-palmitate-->oleil-palmitate-palmitate-->oleil-oleil-palmitate-->oleil-oleil-oleate. The shift to the left and to the right is discerned with this spectrum of isoforms of triglycerides. The shift to the left into direction of palmitinicc triglycerides occurs in case of eating of animal food (i.e. beef andfoodstuf of fat saw milk) when the content of palmitinic saturated fatty acid supersedes 15% of fatty acids total and under the development of endogenic syndrome of insulin resistance. The content of low density lipoproteins cholesterol is high in blood The shift to the right with prevalence of oleinic triglycerides occurs in case of low content of beef and foodstuff of fat saw milk in food, fish eating, seafood and olive oil. The physiologic levels of carbohydrates in food and insulin function are present too. The shift to the right initiates the action of insulin, ometa-3 essential polyenic fatty acids, glytazones and fibrates. They increase the activity of delta9-stearil-KoA-desaturase-2 and the transformation of palmitine saturated fatty acid into mono unsaturated oleinic fatty acid. The shift to the left forms the palmitine alternative of metabolism of substrate to supply cells with energy. The shift to the right is a more effective oleinic alternative.

Evaluation of genome-wide association study results through development of ontology fingerprints

PubMed Central

Tsoi, Lam C.; Boehnke, Michael; Klein, Richard L.; Zheng, W. Jim

2009-01-01

Motivation: Genome-wide association (GWA) studies may identify multiple variants that are associated with a disease or trait. To narrow down candidates for further validation, quantitatively assessing how identified genes relate to a phenotype of interest is important. Results: We describe an approach to characterize genes or biological concepts (phenotypes, pathways, diseases, etc.) by ontology fingerprint—the set of Gene Ontology (GO) terms that are overrepresented among the PubMed abstracts discussing the gene or biological concept together with the enrichment p-value of these terms generated from a hypergeometric enrichment test. We then quantify the relevance of genes to the trait from a GWA study by calculating similarity scores between their ontology fingerprints using enrichment p-values. We validate this approach by correctly identifying corresponding genes for biological pathways with a 90% average area under the ROC curve (AUC). We applied this approach to rank genes identified through a GWA study that are associated with the lipid concentrations in plasma as well as to prioritize genes within linkage disequilibrium (LD) block. We found that the genes with highest scores were: ABCA1, lipoprotein lipase (LPL) and cholesterol ester transfer protein, plasma for high-density lipoprotein; low-density lipoprotein receptor, APOE and APOB for low-density lipoprotein; and LPL, APOA1 and APOB for triglyceride. In addition, we identified genes relevant to lipid metabolism from the literature even in cases where such knowledge was not reflected in current annotation of these genes. These results demonstrate that ontology fingerprints can be used effectively to prioritize genes from GWA studies for experimental validation. Contact: zhengw@musc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19349285

The Associations of Indices of Obesity with Lipoprotein Subfractions in Japanese American, African American and Korean Men

PubMed Central

Hirooka, Nobutaka; Shin, Chol; Masaki, Kamal H.; Edmundowicz, Daniel; Choo, Jina; Barinas-Mitchell, Emma J.M.; Willcox, Bradley J.; Sutton-Tyrrell, Kim; El-Saed, Aiman; Miljkovic-Gacic, Iva; Ohkubo, Takayoshi; Miura, Katsuyuki; Ueshima, Hirotsugu; Kuller, Lewis H.; Sekikawa, Akira

2013-01-01

Background Both indices of obesity and lipoprotein subfractions contribute to coronary heart disease risk. However, associations between indices of obesity and lipoprotein subfractions remain undetermined across different ethnic groups. This study aims to examine the associations of indices of obesity in Japanese Americans (JA), African Americans (AA) and Koreans with lipoprotein subfractions. Methods A population-based sample of 230 JA, 91 AA, and 291 Korean men aged 40–49 was examined for indices of obesity, i.e., visceral and subcutaneous adipose tissue (VAT and SAT, respectively), waist circumference (WC), and body-mass index (BMI), and for lipoprotein subfractions by nuclear-magnetic-resonance spectroscopy. Multiple regression analyses were performed in each of the three ethnic groups to examine the associations of each index of obesity with lipoprotein. Results VAT had significant positive associations with total and small low-density lipoprotein (LDL) and a significant negative association with large high-density lipoprotein (HDL) in all three ethnicities (p < 0.01). SAT, WC, and BMI had significant positive associations with total and small LDL in only JA and Koreans, while these indices had significant inverse associations with large HDL in all ethnic groups (p < 0.01). Compared to SAT, VAT had larger R2 values in the associations with total and small LDL and large HDL in all three ethnic groups. Conclusions VAT is significantly associated with total and small LDL and large HDL in all three ethnic groups. The associations of SAT, WC, and BMI with lipoprotein subfractions are weaker compared to VAT in all three ethnic groups. PMID:25068101

Elevated blood lipids are uncommon in patients with post-polio syndrome--a cross sectional study.

PubMed

Melin, Eva; Kahan, Thomas; Borg, Kristian

2015-04-29

The post-polio syndrome occurs in people who previously have had poliomyelitis. After the initial recovery, new or increasing neurologic symptoms occur. Inflammation and dyslipidaemia may play an important role in the development of atherosclerotic complications, for example myocardial infarction and angina pectoris. Previous studies on cardiovascular risk factors in the post-polio syndrome have found a higher prevalence of hypertension, ischemic heart disease, hyperlipidaemia, and stroke in these patients. The present study was undertaken in order to evaluate whether post-polio patients have elevated lipid values, and if blood lipid abnormalities could be correlated to signs of inflammation. Cross-sectional study of 89 consecutive post-polio patients, (53 women, mean age 65 years) from the Post-Polio Outpatient Clinic, Danderyd University Hospital, Stockholm, Sweden. The lipid profiles of post-polio patients were compared to age and sex matched reference values from two earlier studies. Statistical analyses were performed by the Student's t-test, and linear regression analyses were assessed by Pearson's correlation coefficient. Mean total cholesterol levels (5.7 mmol/L) were low or normal in post-polio patients, whereas low density lipoprotein levels (3.6 mmol/L) were normal, and high density lipoprotein (1.5 mmol/L) and triglycerides (1.4 mmol/L) lower than reference values. The prevalence of diabetes (7%), hypertension (38%), concomitant cardiovascular disease, (including angina pectoris, myocardial infarction, heart failure, atrial fibrillation and stroke) (7%), and calculated 10 year risk of coronary heart disease according to Framingham risk score algorithm (8%) was not increased in post-polio patients. Compared to reference populations, post-polio patients in Sweden appear to have low or normal total cholesterol and low density lipoprotein levels, whereas high density lipoprotein and triglyceride levels are low. Hence, a possible persisting inflammatory process in post-polio syndrome does not seem to be associated with increased lipids and an increased risk for coronary heart disease events.

MicroRNA 302a is a novel modulator of cholesterol homeostasis and atherosclerosis.

PubMed

Meiler, Svenja; Baumer, Yvonne; Toulmin, Emma; Seng, Kosal; Boisvert, William A

2015-02-01

Macrophage foam cell formation is a key feature of atherosclerosis. Recent studies have shown that specific microRNAs (miRs) are regulated in modified low-density lipoprotein-treated macrophages, which can affect the cellular cholesterol homeostasis. Undertaking a genome-wide screen of miRs regulated in primary macrophages by modified low-density lipoprotein, miR-302a emerged as a potential candidate that may play a key role in macrophage cholesterol homeostasis. The objective of this study was to assess the involvement of miR-302a in macrophage lipid homeostasis and if it can influence circulating lipid levels and atherosclerotic development when it is inhibited in a murine atherosclerosis model. We found that transfection of primary macrophages with either miR-302a or anti-miR-302a regulated the expression of ATP-binding cassette (ABC) transporter ABCA1 mRNA and protein. Luciferase reporter assays showed that miR-302a repressed the 3' untranslated regions (UTR) activity of mouse Abca1 by 48% and human ABCA1 by 45%. In addition, transfection of murine macrophages with miR-302a attenuated cholesterol efflux to apolipoprotein A-1 (apoA-1) by 38%. Long-term in vivo administration of anti-miR-302a to mice with low-density lipoprotein receptor deficiency (Ldlr(-/-)) fed an atherogenic diet led to an increase in ABCA1 in the liver and aorta as well as an increase in circulating plasma high-density lipoprotein levels by 35% compared with that of control mice. The anti-miR-302a-treated mice also displayed reduced atherosclerotic plaque size by ≈25% and a more stable plaque morphology with reduced signs of inflammation. These studies identify miR-302a as a novel modulator of cholesterol efflux and a potential therapeutic target for suppressing atherosclerosis. © 2014 American Heart Association, Inc.

Cholesterol and Triglycerides in Antipsychotic-Naive Patients with Nonaffective Psychosis

PubMed Central

Kirkpatrick, Brian; Garcia-Rizo, Clemente; Tang, Kun; Fernandez-Egea, Emilio; Bernardo, Miguel

2010-01-01

Patients with psychosis have an increased prevalence of hyperlipidemia. We compared fasting concentrations of lipids in newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis (N-87) and control subjects (N=92). After accounting for gender, age, smoking, socioeconomic status, and body mass index, there was no significant difference between the two groups in total cholesterol, high-density lipoproteins, low-density lipoproteins, or triglycerides. PMID:20576293

Impact of acculturation on cardiovascular risk factors among elderly Mexican Americans.

PubMed

López, Lenny; Peralta, Carmen A; Lee, Anne; Zeki Al Hazzouri, Adina; Haan, Mary N

2014-10-01

Higher levels of acculturation among Latinos have been shown to be associated with a higher prevalence of cardiovascular (CV) risk factors in some studies of middle-age persons. The association of acculturation and prevalence of CV risk factors in elderly Latinos is less well established. Acculturation was measured using the validated bidimensional Acculturation Rating Scale for Mexican Americans-II. We conducted a cross-sectional analysis of the association of acculturation with prevalence of CV risk factors among 1789 elderly men and women from the Sacramento Area Latino Study on Aging using multivariate linear and logistic regression. We tested for the interaction of acculturation with risk factors by nativity status. Median age was 69.8 years. Higher acculturation was associated with lower systolic blood pressure, lower low-density lipoprotein, higher high-density lipoprotein, and lower prevalence of CV disease after age and sex adjustment. Higher acculturation remained associated with lower level of low-density lipoprotein and higher level of high-density lipoprotein after full adjustment. Nativity status did not affect these results. Contrary to other reports in middle-aged persons, higher levels of acculturation were associated with better lipid profiles and no significant differences in other CV risk factors by acculturation level in elderly Latinos. Copyright © 2014 Elsevier Inc. All rights reserved.

Serum amyloid A stimulates macrophage foam cell formation via lectin-like oxidized low-density lipoprotein receptor 1 upregulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Ha Young, E-mail: hayoung@skku.edu; Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714; Kim, Sang Doo

2013-03-29

Highlights: ► SAA induced macrophage foam cell formation. ► SAA stimulated upregulation of lectin-like oxidized low-density lipoprotein receptor 1 (LOX1). ► SAA-induced LOX1 expression and foam cell formation is mediated by JNK/NF-κB signaling. ► HDL-conjugated SAA also stimulates foam cell formation via LOX1 upregulation. ► The finding reveals a novel mechanism of action of SAA in the pathogenesis of atherosclerosis. -- Abstract: Elevated levels of serum amyloid A (SAA) is a risk factor for cardiovascular diseases, however, the role of SAA in the pathophysiology of atherosclerosis remains unclear. Here we show that SAA induced macrophage foam cell formation. SAA-stimulated foammore » cell formation was mediated by c-jun N-terminal kinase (JNK) signaling. Moreover, both SAA and SAA-conjugated high density lipoprotein stimulated the expression of the important scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) via nuclear factor-κB (NF-κB). A LOX1 antagonist carrageenan significantly blocked SAA-induced foam cell formation, indicating that SAA promotes foam cell formation via LOX1 expression. Our findings therefore suggest that SAA stimulates foam cell formation via LOX1 induction, and thus likely contributes to atherogenesis.« less

Cannabinoids impair the formation of cholesteryl ester in cultured human cells.

PubMed

Cornicelli, J A; Gilman, S R; Krom, B A; Kottke, B A

1981-01-01

The ability of cultured human fibroblasts to form cholesteryl esters from 14C-oleate is impaired by delta'-tetrahydrocannabinol, cannabidiol, and cannabinol, a group of natural products isolated from Cannabis sativa. This inhibition is compound and dose-related; 30 microM cannabidiol reduced esterification to less than 20% of the control values. The esterification of endogenous and exogenous cholesterol was affected, since inhibition was seen with either low density lipoproteins (200 micrograms/ml) or 25-hydroxycholesterol (5 micrograms/ml) as esterification stimuli. Cells treated with these compounds at doses of from 1 to 30 microM showed no impairment of protein synthesis, triglyceride or phospholipid formation, or ability to metabolize 125I-low density lipoproteins. An inhibition of cholesterol esterification was seen in human aortic medial cells. With increasing doses of these compounds, low density lipoproteins (25 micrograms/ml) became progressively less effective in suppressing HMG-CoA reductase in cultured human fibroblasts; with 30 microM cannabidiol the enzyme suppression was only 24% of that found in cells incubated with low density lipoproteins in the absence of drugs. Based on these data, we conclude that the cannabinoids "compartmentalize" cholesterol and, thus, make is unavailable for regulating cellular cholesterol metabolism. This may occur as a result of enhanced sterol efflux.

Serum lipoprotein (a) concentrations among Arab children: a hospital-based study in Kuwait.

PubMed

Alsaeid, M; Alsaeid, K; Fatania, H R; Sharma, P N; Abd-Elsalam, R

1998-09-01

Elevated lipoprotein (a) [Lp(a)] is an independent risk factor for premature atherosclerosis and coronary heart disease, both of which are prevalent among Kuwaitis. Our objective was to measure serum lipids, including Lp(a), in Arab children and compare them with values reported for other ethnic groups. To that end, serum concentrations of Lp(a), total cholesterol [T-CHOL], high density lipoprotein [HDL], low density lipoprotein [LDL], and triglyceride [TG] were assessed in 103 Arab children. The mean and median Lp(a) were 140.4 mg/l and 95 mg/l, respectively. The Lp(a) frequency distribution was skewed to the right with the highest frequencies appearing at low levels. Serum Lp(a) correlated positively with T-CHOL and LDL but did not correlate with age, HDL and TG. Only nine children (8.7%) had serum Lp(a) levels associated with increased cardiovascular risk, namely > or = 300 mg/l.

A high-density lipoprotein-mediated drug delivery system.

PubMed

Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

2016-11-15

High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

Serum lipoprotein (a) concentration in patients with nephrotic syndrome and its clinical implication.

PubMed

Yang, X; Wang, H; Zhu, Z; Deng, A

1998-01-01

Serum lipoprotein(a) [Lp(a)] concentration was determined in 42 patients with primary nephrotic syndrome (NS) and the relationships between Lp (a) and plasma lipids, apolipoproteins, serum creatinine (Scr), albumin, urinary proteins (Upro) were also analyzed. The results showed that: (1) serum Lp(a) concentrations in the patients with NS were higher than those in healthy controls; (2) the levels of serum Lp(a) were correlated positively with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein B (Apo-B), Upros (Upro). It is concluded that the NS patients had the potential risk of suffering from coronary artery disease, glomerular sclerosis and thrombosis. The remission of NS may partially decrease the serum Lp(a) levels. Further studies are needed to explore the prevention and treatment of dislipedemia in patients with NS.

The Success Story of LDL Cholesterol Lowering.

PubMed

Pedersen, Terje R

2016-02-19

We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. © 2016 American Heart Association, Inc.

Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

USDA-ARS?s Scientific Manuscript database

Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

Secondary hypertriglyceridemia in children and adolescents.

PubMed

Blackett, Piers R; Wilson, Don P; McNeal, Catherine J

2015-01-01

Secondary dyslipidemia with predominant hypertriglyceridemia may occur as a consequence of both common and rare causes. After accounting for obesity and associated insulin resistance, clinicians should carefully consider other contributing factors and conditions. Genetic background and causative factors prevail during gestation, infancy, and childhood and continue in adults. Elevations in triglyceride (TG) are associated with transfer of TG to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) resulting in lipolysis, HDL degradation, and formation of atherogenic LDL particles. Defining and treating the underlying cause is the first step toward restoring the lipids and lipoproteins to normal, especially in cases with severe hypertriglyceridemia, who are at risk for acute pancreatitis. Disorders involving the liver, kidney, endocrine, and immune systems and medications need to be considered. Rare diseases such as lipodystrophy and glycogen storage disease are particularly challenging, and there have been promising new developments. Treatment depends on the severity; prevention of acute pancreatitis being a priority in severe cases and lifestyle modification being a foundation for general management followed by targeting TG and predictors of coronary artery disease such as LDL cholesterol and non-HDL cholesterol, when they exceed cutpoints. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[The role of lipoprotein-associated enzyme paraoxonase 1 and its polymorphisms in the pathogenesis of endothelial dysfunction and somatic complications in patients with alcoholism: Review ].

PubMed

Panchenko, L F; Baronets, V Yu; Naumova, T A; Pyrozhkov, S V; Terebilina, N N; Shoibonov, B B

2016-01-01

A review of recent data on the role of the multifunctional enzyme, associated with high density lipoproteins - paraoxonase 1 (PON1) in maintaining healthy endothelial function by detoxifying both oxidized low density lipoproteins and homocysteine thiolactone. The additional contribution to the protection of the endothelium against damage makes organophosphatase activity of PON1 involved in the detoxification products of tobacco smoke. The reduction of antioxidant activity of PON1 promotes the differentiation of monocytes into macrophages and the development of inflammation. The reduction of thiolactonase activity of PON1 is accompanied by a decrease of methionine re-synthesis from homocysteine causing DNA- hypomethylation and alteratioin of the expression patterns of pro- and anti-atherogenic genes. Global hypomethylation of the genome is regarded as one of the three most important mechanisms of the increased risk of somatic complications of alcoholism. The accumulation of homocysteine thiolactone serving agonist of glutamate receptors and antagonist of dopamine receptors is a prerequisite to increased alcohol abuse. Clinical observations focusing on gene polymorphisms of PON indicate that three different genotypes of polymorphism PON1Q192R have unequal degrees atheroprotective properties.

Loss of LCAT activity in the golden Syrian hamster elicits pro-atherogenic dyslipidemia and enhanced atherosclerosis.

PubMed

Dong, Zhao; Shi, Haozhe; Zhao, Mingming; Zhang, Xin; Huang, Wei; Wang, Yuhui; Zheng, Lemin; Xian, Xunde; Liu, George

2018-06-01

Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis. CRISPR/CAS9 gene editing system was employed to generate mutant LCAT hamsters. The characteristics of lipid metabolism and the development of atherosclerosis in the mutant hamsters were investigated using various conventional methods in comparison with wild type control animals. Hamsters lacking LCAT activity exhibited pro-atherogenic dyslipidemia as diminished high density lipoprotein (HDL) and ApoAI, hypertriglyceridemia, Chylomicron/VLDL accumulation and significantly increased ApoB100/48. Mechanistic study for hypertriglyceridemia revealed impaired LPL-mediated lipolysis and increased very low density lipoprotein (VLDL) secretion, with upregulation of hepatic genes involved in lipid synthesis and transport. The pro-atherogenic dyslipidemia in mutant hamsters was exacerbated after high fat diet feeding, ultimately leading to near a 3- and 5-fold increase in atherosclerotic lesions by aortic en face and sinus lesion quantitation, respectively. Our findings demonstrate that LCAT deficiency in hamsters develops pro-atherogenic dyslipidemia and promotes atherosclerotic lesion formation. Published by Elsevier Inc.

Paraoxonase: The Universal Factor of Antioxidant Defense in Human Body.

PubMed

Borovkova, E I; Antipova, N V; Komeenko, T V; Shakhparonov, M I; Borovkov, I M

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents.

Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial.

PubMed

Mora, Samia; Caulfield, Michael P; Wohlgemuth, Jay; Chen, Zhihong; Superko, H Robert; Rowland, Charles M; Glynn, Robert J; Ridker, Paul M; Krauss, Ronald M

2015-12-08

Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo. In 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio [HR] per SD, 1.03; 95% confidence interval [CI], 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk. In JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and LDL particles. During high-intensity statin therapy, on-treatment levels of LDL-C and atherogenic particles were associated with residual risk of CVD/all-cause death. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. © 2015 American Heart Association, Inc.

Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure.

PubMed

Yang, Mu; Liu, Yingye; Dai, Jian; Li, Lin; Ding, Xin; Xu, Zhe; Mori, Masayuki; Miyahara, Hiroki; Sawashita, Jinko; Higuchi, Keiichi

2018-04-04

During acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2 -/- ) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR. AA amyloid deposition was suppressed in Apoa2 -/- mice compared with wild type (WT) mice. During APR, Apoa2 -/- mice exhibited significant suppression of serum SAA levels and hepatic Saa1 and Saa2 mRNA levels. Pathological investigation showed Apoa2 -/- mice had less tissue damage and less inflammatory cell infiltration during APR. Total lipoproteins were markedly decreased in Apoa2 -/- mice, while the ratio of HDL to low density lipoprotein (LDL) was also decreased. Both WT and Apoa2 -/- mice showed increases in LDL and very large HDL during APR. SAA was distributed more widely in lipoprotein particles ranging from chylomicrons to very small HDL in Apoa2 -/- mice. Our observations uncovered the critical roles of ApoA-II in inflammation, serum lipoprotein stability and AA amyloidosis morbidity, and prompt consideration of therapies for AA and other amyloidoses, whose precursor proteins are associated with circulating HDL particles.

De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients.

PubMed

Idowu, Michael O; Chhatrala, Ravi; Siddiqui, M Bilal; Driscoll, Carolyn; Stravitz, R Todd; Sanyal, Arun J; Bhati, Chandra; Sargeant, Carol; Luketic, Velimir A; Sterling, Richard K; Contos, Melissa; Matherly, Scott; Puri, Puneet; Siddiqui, M Shadab

2015-11-01

Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P < 0.001), sdLDL-C to low-density lipoprotein cholesterol ratio (32.6 ± 11.6 versus 24.6 ± 10.2; P < 0.01), small-dense low-density lipoprotein particle concentration (sdLDL-P; 770 ± 440 versus 486 ± 402 nmol/L; P < 0.01), very low density lipoprotein particle concentration (VLDL-P; 7.90 ± 7.91 versus 3.86 ± 3.18 nmol/L; P < 0.01), and very low density lipoprotein size (VLDL-size; 51.9 ± 6.4 versus 48.7 ± 6.3 nm; P = 0.06). LTRs with hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P < 0.01) but similar fasting glucose and hemoglobin A1c. Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors. © 2015 American Association for the Study of Liver Diseases.

Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis

PubMed Central

Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

2010-01-01

The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis. PMID:21197233

Methionine deficiency in rats fed soy protein induces hypercholesterolemia and potentiates lipoprotein susceptibility to peroxidation.

PubMed

Moundras, C; Rémésy, C; Levrat, M A; Demigné, C

1995-09-01

A number of studies have provided evidence that plant proteins, especially soy protein, have a cholesterol-lowering effect as compared with casein. However, dietary supply of sulfur amino acids may be deficient when soy protein is present in the diet at a suboptimal level, which could affect lipid metabolism. Accordingly, in rats fed 13% protein diets, soy protein feeding resulted in a cholesterol-increasing effect (+18%), which could be counteracted by methionine supplementation (0.4%). In contrast, soy protein was effective in decreasing plasma triglyceride, as compared with levels in rats fed casein; this triglyceride-lowering effect was entirely abolished by methionine supplementation. The hypercholesterolemic effect of soy protein was characterized by a higher cholesterol content in low-density lipoprotein (LDL) and high-density lipoprotein 1 (HDL1) fractions, together with a marked induction of hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase activity and to a lesser extent cholesterol 7 alpha-hydroxylase. There was practically no induction of these enzymes, as compared with levels in rats fed casein diets, when the soy protein diet was supplemented with methionine. Very-low-density lipoprotein (VLDL) plus LDL susceptibility to peroxidation was higher in rats fed soy protein than in casein-fed rats, which could reflect in part the lack of sulfur amino acid availability, since methionine supplementation led to a partial recovery of lipoprotein resistance to peroxidation. These findings suggest that amino acid imbalance could be atherogenic by increasing circulating cholesterol and leading to a higher lipoprotein susceptibility to peroxidation.

On-line miniaturized asymmetrical flow field-flow fractionation-electrospray ionization-tandem mass spectrometry with selected reaction monitoring for quantitative analysis of phospholipids in plasma lipoproteins.

PubMed

Yang, Iseul; Kim, Ki Hun; Lee, Ju Yong; Moon, Myeong Hee

2014-01-10

A direct analytical method for high speed quantitative analysis of lipids in human blood plasma using on-line chip-type asymmetrical flow field-flow fractionation-electrospray ionization-tandem mass spectrometry (cAF4-ESI-MS/MS) with selected reaction monitoring (SRM) is described in this study. Utilizing a miniaturized cAF4 channel, high speed size separation of high density lipoproteins (HDL) and low density lipoproteins (LDL) from plasma samples can be accomplished at a microflow rate along with simultaneous desalting of lipoproteins, both of which are conducive to direct ESI of lipids in lipoproteins. This study demonstrates that the SRM method to monitor phospholipids during cAF4-ESI-MS/MS can be successfully applied to the quantitation of lipid molecules in plasma lipoproteins without the need of a separate lipid extraction process. For quantitation of lipids in HDL and LDL during cAF4-ESI-MS/MS runs, a protein standard (carbonic anhydrase, 29 kDa) was added to each plasma sample as an internal standard such that a peak intensity of y67(+5) ions, which are high abundant SRM product ions of CA, could be utilized to calculate the relative intensity of each lipid molecule. The developed method was applied to plasma samples from 10 patients with coronary artery disease (CAD) and 10 healthy control samples, and quantitative analysis of 39 lipid molecules including phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, phosphatidylglycerols, and phosphatidylinositols, resulted in the selection of 13 PL species showing more than 2.5 fold difference in relative abundance (p<0.01) between the groups. The present study demonstrates a high speed analytical method for determining plasma lipid content and distribution without an organic solvent extraction of lipids from plasma. Copyright © 2013 Elsevier B.V. All rights reserved.

Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country.

PubMed

Khoo, Kah Lin; Page, Michael M; Liew, Yin Mei; Defesche, Joep C; Watts, Gerald F

2016-01-01

Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014. We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH. We treated 13 women and 2 men aged 6 to 59 years, 10 with homozygous and 5 with heterozygous FH, all on maximally tolerated cholesterol-lowering drug therapy, for a total of 65 patient-years. Acute lowering of low-density lipoprotein cholesterol post apheresis was 56.3 ± 7.2%, with time-averaged mean lowering of 34.9 ± 13.9%. No patients experienced any cardiovascular events during the period of receiving LA. Patients receiving LA experienced few side effects and enjoyed reasonable quality of life, but inability to continue treatment was frequent because of cost. LA for severe FH can be delivered effectively in the short term in developing nations, but costs are a major barrier to sustaining this mode of treatment for this high-risk group of patients. New drug therapies for FH, such as the proprotein convertase subtilisin/kexin type 9 inhibitors, microsomal triglyceride transfer protein inhibitors, and apolipoprotein-B100 antisense oligonucleotides may allow improved care for these patients, but costs and long-term safety remain as issues to be addressed. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[Inflammatory process in atherogenesis: new facts about old flame].

PubMed

Vucević, Danijela; Radak, Dorde; Radosavljević, Tatjana; Mladenović, Dusan; Milovanović, Ivan

2012-01-01

INTRODUCTION. Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Pathogenesis of this disease is not fully understood. Endothelial Dysfunction and Inflammatory Process. Endothelial dysfunction is recognized as the crucial step in atherogenesis. A lot of studies have confirmed the involvement of various mediators of inflammation in initial proatherogenic processes, such as the upregulation of adhesion molecules on endothelial cells, binding of low density lipoproteins to endothelium, activation of macrophages and proliferation of vascular smooth muscle cells. Fatty stain and Inflammatory Process. Fatty stain consists of foam cell accumulation. After foam cell formation, mediators of inflammation initiate a series ofintracellular events that include the induction of inflammatory cytokines. Thus, a vicious circle of inflammation, modification of lipoproteins and further inflammation can be maintained in the artery. Transitory Lesion and Inflammatory Process. In transitory lesion intensive phagocytosis of oxidized low density lipoproteins additionally activates monocytes and macrophages and consequently facilitates and exacerbates the inflammatory response. Fibrotic Plaque and Inflammatory Process. Inflammatory process, matrix-degrading metalloproteinases activity, platelets aggregation and smooth muscle cells proliferation play a central role in development of fibrotic plaque. Complex Lesion and Inflammatory Process. It has been shown that inflammation is closely related to the development of atherosclerotic plaque rupture. The contribution of inflammatory process has become increasingly meaningful in understanding the initiation, progression and clinical manifestations ofatherosclerosis.

Liver-specific inhibition of acyl-coenzyme a:cholesterol acyltransferase 2 with antisense oligonucleotides limits atherosclerosis development in apolipoprotein B100-only low-density lipoprotein receptor-/- mice.

PubMed

Bell, Thomas A; Brown, J Mark; Graham, Mark J; Lemonidis, Kristina M; Crooke, Rosanne M; Rudel, Lawrence L

2006-08-01

The purpose of this study was to determine the effects of liver-specific inhibition of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) on the development of hypercholesterolemia and atherosclerosis in mice. Apolipoprotein B100-only low-density lipoprotein (LDL) receptor-/- mice were given saline, a nontargeting control antisense oligonucleotide (ASO), or ASOs targeting ACAT2 biweekly for a period spanning 16 weeks. Mice treated with ACAT2 targeting ASOs had liver-specific reduction in ACAT2 mRNA, yet intestinal ACAT2 and cholesterol absorption was left undisturbed. ASO-mediated knockdown of ACAT2 resulted in reduction of total plasma cholesterol, increased levels of plasma triglyceride, and a shift in LDL cholesteryl ester (CE) fatty acid composition from mainly saturated and monounsaturated to polyunsaturated fatty acid enrichment. Furthermore, the liver-specific depletion of ACAT2 resulted in protection against diet-induced hypercholesterolemia and aortic CE deposition. This is the first demonstration that specific pharmacological inhibition of ACAT2, without affecting ACAT1, is atheroprotective. Hepatic ACAT2 plays a critical role in driving the production of atherogenic lipoproteins, and therapeutic interventions, such as the ACAT2-specific ASOs used here, which reduce acyltransferase 2 (ACAT2) function in the liver without affecting ACAT1, may provide clinical benefit for cardiovascular disease prevention.

The effect of insulin deficiency on the plasma clearance and exchange of high-density-lipoprotein phosphatidylcholine in rats.

PubMed Central

Martins, I J; Redgrave, T G

1992-01-01

Triolein/cholesteryl oleate/cholesterol/phosphatidylcholine emulsions designed to model the lipid composition of chylomicrons were injected intravenously into control and streptozotocin-treated insulin-deficient rats. As previously described for lymph chylomicrons, the emulsion triolein was hydrolysed and phosphatidylcholine was transferred to the plasma high-density lipoproteins (HDL). This mechanism was used to introduce a phospholipid label into HDL in vivo. The subsequent clearance of phospholipid radioactivity from the plasma of insulin-deficient rats was significantly slower than in controls (P less than 0.025). Plasma clearance was similarly slower in insulin-deficient rats after injection of HDL that was previously labelled with radioactive phospholipids. After injection, the phospholipid label redistributed rapidly between the large-particle fraction of plasma lipoproteins (very-low- and low-density lipoproteins), and the lighter and heavier fractions of HDL. Compared with control rats, in insulin-deficient rats less of the phospholipid label was distributed to the lighter HDL fraction and more to the heavier HDL fraction, and this difference was not due to changes in activity of lecithin: cholesterol acyltransferase or in the apparent activity of phospholipid transfer protein. In insulin-deficient rats the changes in HDL phospholipid clearance and exchange appeared to be secondary to the associated hypertriglyceridaemia and the related changes in distribution of phospholipids between classes of plasma lipoproteins. PMID:1536661

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

PubMed Central

Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

2013-01-01

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

[Relationship between Ghrelin polymorphism and serum lipoprotein levels in Han Chinese with or without coronary heart disease risk factors].

PubMed

Xie, Xuan; Zhang, Jing; Wang, Yu-huan; Wang, Jun-hong; Zhang, Chun-hong; Ni, Hong-yan; Yuan, Xiao-hong

2008-04-01

To investigate the relationship between polymorphism of Ghrelin gene and serum levels of lipoprotein in Han Chinese with or without coronary heart disease (CHD) risk factors. PCR restriction fragment length polymorphism assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk factors served as normal controls. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were measured to analyze the relationship with the polymorphism of Ghrelin gene. Ghrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976, 0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL-C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg carriers in control group and in the high-risk group (all P < 0.05). Arg/Gln carriers were associated lower HDL-C levels in Han Chinese.

Paraoxonase responses to exercise and niacin therapy in men with metabolic syndrome.

PubMed

Taylor, James Kyle; Plaisance, Eric P; Mahurin, A Jack; Mestek, Michael L; Moncada-Jimenez, Jose; Grandjean, Peter W

2015-01-01

Our purpose was to characterize changes in paraoxonase 1 (PON1) activity and concentration after single aerobic exercise sessions conducted before and after 6 weeks of niacin therapy in men with metabolic syndrome (MetS). Twelve men with MetS expended 500 kcal by walking at 65% of VO2max before and after a 6-week regimen of niacin. Niacin doses were titrated by 500 mg/week from 500 to 1500 mg/day and maintained at 1500 mg/day for the last 4 weeks. Fasting blood samples were collected before and 24 hours after each exercise session and analyzed for PON1 activity, PON1 concentration, myeloperoxidase (MPO), apolipoprotein A1, oxidized low-density lipoprotein (oLDL), lipoprotein particle sizes and concentrations. PON1 activity, PON1 concentration, MPO, and oLDL were unaltered following the independent effects of exercise and niacin (P > 0.05 for all). High-density lipoprotein particle size decreased by 3% (P = 0.040) and concentrations of small very low-density lipoprotein increased (P = 0.016) following exercise. PON1 activity increased 6.1% (P = 0.037) and PON1 concentrations increased 11.3% (P = 0.015) with the combination of exercise and niacin. Exercise and niacin works synergistically to increase PON1 activity and concentration with little or no changes in lipoproteins or markers of lipid oxidation.

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

PubMed

Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of the combination of methyltestosterone and esterified estrogens compared with esterified estrogens alone on apolipoprotein CIII and other apolipoproteins in very low density, low density, and high density lipoproteins in surgically postmenopausal women.

PubMed

Chiuve, Stephanie E; Martin, Lisa A; Campos, Hannia; Sacks, Frank M

2004-05-01

Androgens are known to lower plasma triglycerides, an independent risk factor for coronary heart disease (CHD). Triglycerides are carried in plasma on very low density (VLDL) and low density (LDL) lipoprotein particles. Apolipoprotein CIII (apoCIII), a strong predictor of CHD, impairs the metabolism of VLDL and LDL, contributing to increased triglycerides. The objective of this study was to assess the effect of oral methyltestosterone (2.5 mg/d), added to esterified estrogens (1.25 mg/d), on concentrations of apolipoproteins and lipoproteins, specifically those containing apoCIII, compared with esterified estrogens alone in surgically postmenopausal women. The women in the methyltestosterone plus esterified estrogen group had significant decreases in total triglycerides, apoCI, apoCII, apoCIII, apoE, and high density lipoprotein (HDL) cholesterol compared with those in the esterified estrogen group. The decreases in apoCIII concentrations occurred in VLDL (62%; P = 0.02), LDL (35%; P = 0.001), and HDL (17%; P < 0.0001). There were also decreases in cholesterol and triglycerides concentrations of apoCIII containing LDL, and apoCI concentration of apoCIII containing VLDL. There was no effect on VLDL and LDL particles that did not contain apoCIII or on apoB concentrations. In conclusion, methyltestosterone, when administered to surgically postmenopausal women taking esterified estrogen, has a selective effect to reduce the apoCIII concentration in VLDL and LDL, a predictor of CHD. Methyltestosterone may lower plasma triglycerides through a reduction in apoCIII.

Uptake of acetaldehyde-modified (ethylated) low-density lipoproteins by mouse peritoneal macrophages.

PubMed

Wehr, Hanna; Mirkiewicz, Ewa; Rodo, Maria; Bednarska-Makaruk, Malgorzata

2002-04-01

The uptake of acetaldehyde-modified (ethylated) low-density lipoproteins (LDLs) by murine peritoneal macrophages is described and compared with the uptake of acetylated LDLs. The fluorescent marker DiI was used. No competition between ethylated and acetylated LDLs was observed. Ethylated LDL uptake was not inhibited by polyinosinic acid or fucoidin. Our conclusion is that uptake of ethylated and acetylated LDLs can be done by two different receptors.

Posttraumatic Stress Disorder and Metabolic Syndrome: Retrospective Study of Repatriated Prisoners of War

DTIC Science & Technology

2011-04-01

density lipoprotein (HDL) cholesterol (HDL-C), elevated triglycerides (TGs), and impaired fasting glucose or impaired glucose tolerance. 3 MbS is a...Stress Disorder and Metabolic Syndrome MILITARY MEDICINE, Vol. 176, April 2011 373 targeted at elevated low- density lipoprotein cholesterol , which is... relationship between PTSD and MbS. ACKNOWLEDGMENTS We thank the staff of the Robert E. Mitchell Center for Prisoner of War Studies for the high

The Effect of Aerobic Exercise on Total Cholesterol, High-Density Lipoprotein, Apolipoprotein B, Apolipoprotein A-I, and Percent Body Fat in Adolescent Females.

ERIC Educational Resources Information Center

Lungo, Diane; And Others

The effect of aerobic exercise on total cholesterol (TC), high-density lipoprotein (HDL), apolipoprotein B (Apo B), apolioprotein A-I (Apo A-I), and percent body fat in adolescent females was studied. The control subjects (n=86) were volunteers who had completed a physical education class at least six months prior to the commencement of the study,…

Complex of vitamins and antioxidants protects low-density lipoproteins in blood plasma from free radical oxidation and activates antioxidants enzymes in erythrocytes from patients with coronary heart disease.

PubMed

Konovalova, G G; Lankin, V Z; Tikhaze, A K; Nezhdanova, I B; Lisina, M O; Kukharchuk, V V

2003-08-01

We studied the effect of a complex containing antioxidant vitamins C and E, provitamin A, and antioxidant element selenium on the contents of primary (lipid peroxides) and secondary products (malonic dialdehyde) of free radical lipid oxidation in low-density lipoproteins isolated from the plasma of patients with coronary heart disease and hypercholesterolemia by means of preparative ultracentrifugation. Activity of key antioxidant enzymes in the blood was measured during treatment with the antioxidant preparation. Combination treatment with antioxidant vitamins and antioxidant element selenium sharply decreased the contents of primary and secondary free radical oxidation products in circulating low-density lipoproteins and increased activity of antioxidant enzymes in erythrocytes. Activities of superoxide dismutase and selenium-containing glutathione peroxidase increased 1 and 2 months after the start of therapy, respectively.

In vitro studies of PBT Nonwoven Fabrics adsorbent for the removal of low density lipoprotein from hyperlipemia plasma

NASA Astrophysics Data System (ADS)

Cao, Ye; Wang, Hong; Yang, Chao; Zhong, Rui; Lei, Yu; Sun, Kang; Liu, Jiaxin

2011-06-01

Polyanion ligands such as acrylic acid (AA) and heparin were grafted on PBT Nonwoven Fabrics (PBTNF) to study their effect on the adsorption of low density lipoprotein (LDL). These modified PBTNFs were characterized by Horizontal Attenuated Total Reflectance Fourier Transform Infrared spectroscopy and X-ray Photoelectron spectroscopy. The blood compatibilities of the modified PBTNFs were examined using in vitro hemolysis rate (HR), platelet adhesion, total protein (TP) and activated partial thromboplastin time. The results showed that direct immobilized heparin could improve PBTNF-PAA's blood compatibility and decrease the adsorption capability of useful high density lipoprotein, but would possess so low bioactivity that could not further improve the absorption of LDL and TC. Since the PBTNF-PAA55-Heparin adsorbent had quite good adsorption selectivity for these proteins, it can be an excellent candidate for depletion of LDL with good blood compatibility.

Very low density lipoprotein receptor in Alzheimer disease.

PubMed

Helbecque, N; Amouyel, P

2000-08-15

The apolipoprotein (APO) E4 isoform is associated with an accelerated rate of Alzheimer disease (AD) expression in sporadic as well as late-onset familial forms of the disease but the precise mechanism is unknown. In an attempt to approach the possible mechanisms involved, APOE receptors have been studied. They all belong to the low density lipoprotein (LDL) receptor family and share the same structural motifs. Some of them are preferentially expressed in the brain such as the LDL receptor related protein, the apolipoprotein E receptor 2, and the very low density lipoprotein (VLDL) receptor. These receptors have been suspected to be involved in Alzheimer disease at various levels. Among them, the VLDL receptor was extensively explored. Although genetic studies conducted on a polymorphism in the promoter of the VLDL receptor in Japanese and Caucasian populations gave divergent results, this does not exclude a possible involvement of the VLDL receptor in AD. Copyright 2000 Wiley-Liss, Inc.

A long-duration (118-day) backpacking trip (2669 km) normalizes lipids without medication: a case study.

PubMed

Devoe, Dale; Israel, Richard Gay; Lipsey, Tiffany; Voyles, Wyatt

2009-01-01

To evaluate the effects of a long-distance backpacking trip on body composition, weight, blood lipids, and lipoproteins. Single-subject (male, aged 49 years) study of an experienced backpacker who hiked 118 days on the Appalachian Trail. Outcome measures that were assessed pre-hike and post-hike included body fat (%) by hydrostatic weighing and skinfold assessment, height and weight, body mass index (BMI), circumference measurements (umbilicus, anterior suprailiac, maximum hip, greater trochanter, minimum waist, umbilicus/anterior suprailiac ratio), and blood pressure (systolic and diastolic at rest and peak). Dietary analyses (total kilocalories, protein, carbohydrate, fat, cholesterol, saturated fat, monounsaturated fat, polyunsaturated fat, dietary fiber) were conducted pre-hike, on days 54 through 56, and on days 98 through 100. Blood lipids and lipoproteins (triglycerides, high-density lipoprotein, low-density lipoprotein) were measured pre-hike, on day 89, and post-hike. Pre-post differences showed decreases in body weight, from 85.3 kg to 73.9 kg (-11.4 [-13.4%]); percent body fat, hydrostatic weighing, from 25.18 to 14.31 (-10.87 [-43.2%]); percent body fat, skinfolds (7-site), from 23.79 to 11.61 (12.18 [-51.2%]); and BMI, from 29.37 to 25.46 (-3.91 [-13.3%]). Pre-post differences in blood lipid changes over the course of 118 days were as follows: triglycerides (mg x dL(-1)) fell from 319 to 79 (-240 [-75%]); total cholesterol (mg x dL(-1)) fell from 276 to 196 (-80 [-29%]); high-density lipoprotein (HDL) (mg x dL(-1)) rose from 46 to 63 (+17 [+37%]); low-density lipoprotein (LDL) (mg.dL(-1)) fell from 167 to 118 (-49 [-29%]); LDL/HDL ratio fell from 3.63 to 1.87 (-1.76 [-48%]); and total cholesterol/HDL ratio fell from 6.00 to 3.11 (-2.89 [-48%]). The physical activity and diet associated with an extended backpacking adventure can considerably reduce and clinically normalize blood lipids and lipoproteins without medication and can very positively affect body composition and weight.

Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipoprotein cholesterol, and related variables.

PubMed

Maki, Kevin C; Bobotas, George; Dicklin, Mary R; Huebner, Margie; Keane, William F

Long-chain omega-3 fatty acid concentrate pharmaceuticals are used in the United States for treatment of severe hypertriglyceridemia (≥500 mg/dL) and are under investigation as adjuncts to statins for lowering cardiovascular risk in patients with high triglycerides (TGs; 200-499 mg/dL). To evaluate MAT9001, an investigational prescription-only omega-3 fatty acid agent containing predominantly eicosapentaenoic acid (EPA) and docosapentaenoic acid, in 42 men and women with fasting TG 200 to 400 mg/dL. In this open-label, crossover trial, subjects received MAT9001 and EPA ethyl esters (EPA-EE) in random order. They were housed in a clinical research unit for 2 14-day treatment periods, separated by a ≥35-day washout. Lipoprotein lipids, apolipoproteins (Apos) and proprotein convertase subtilisin kexin type 9 levels were measured before and at the end of each treatment period. MAT9001, compared with EPA-EE, resulted in significantly (P < .05) larger reductions from pretreatment levels for TG (-33.2% vs -10.5%), total cholesterol (-9.0% vs -6.2%), non-high-density lipoprotein cholesterol (-8.8% vs -4.6%), very low-density lipoprotein cholesterol (-32.5% vs -8.1%), Apo C3 (-25.5% vs -5.0%), and proprotein convertase subtilisin kexin type 9 (-12.3% vs +8.8%). MAT9001 also produced a significantly (P = .003) larger reduction in Apo A1 (-15.3% vs -10.2%), but responses for high-density lipoprotein cholesterol (-11.3% vs -11.1%), low-density lipoprotein cholesterol (-2.4% vs -4.3%), and Apo B (-3.8% vs -0.7%), respectively, were not significantly different relative to EPA-EE. MAT9001 produced significantly larger reductions than EPA-EE in several lipoprotein-related variables that would be expected to favorably alter cardiovascular disease risk in men and women with hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Diet and waist-to-hip ratio: important predictors of lipoprotein levels in sedentary and active young men with no evidence of cardiovascular disease.

PubMed

Mansfield, E; McPherson, R; Koski, K G

1999-11-01

Healthy, young men were studied to determine the relationship of energy and nutrient intake and physical activity to concentrations of plasma lipoprotein and cholesteryl ester transfer protein. A cross-sectional study compared active and sedentary male subjects (17 to 35 years old) with no personal or family history of coronary heart disease. Participants kept 20-day food and activity journals. Individual intakes of energy, protein, carbohydrate, fat, saturated fat, monounsaturated fatty acids, polyunsaturated fatty acids, dietary fiber, and alcohol were evaluated. Measurements of blood lipids (total cholesterol and triglycerides, high- and low-density lipoprotein cholesterol); apolipoproteins; cholesteryl ester transfer protein; anthropometric variables (body mass index, waist-to-hip ratio, percentage of body fat); and aerobic capacity were taken during fall and spring data collection periods. SUBJECT SELECTION: Subjects were selected on the basis of normal blood lipid levels, absence of underlying disease, and willingness to comply with their current level of physical activity for the duration of the study. Minimal sample size for statistical power was 12 men per group: 12 of 15 subjects who exercised and 13 of 15 subjects who were sedentary completed all phases of the study. Statistical analyses consisted of 2-way analysis of variance (activity level and season). Pearson product moment correlations and multiple regression analyses were conducted to assess whether energy and nutrient intakes, physical activity status, and/or anthropometric variables predicted plasma concentrations of lipids and apolipoproteins. Lower waist-to-hip ratio, and not specifically activity level, was associated with higher levels of high-density lipoprotein cholesterol (HDL-C) and lower levels of low-density lipoprotein cholesterol (LDL-C). Dietary intake of saturated and monounsaturated fats and alcohol predicted changes in some apolipoprotein and lipoprotein levels. Use of waist-to-hip ratio in the primary prevention of coronary heart disease is a simple and cost-effective measure to predict development of abnormal lipoprotein profiles in young men. Specific dietary recommendations include adoption of a heart-healthy diet with emphasis on monounsaturated fatty acids (10% to 12% of energy or one third of total fat intake) and the suggestion that small amounts of alcohol (< 3 drinks per week) may, indeed, be beneficial. Because alcohol and waist-to-hip ratio were both important predictors of LDL-C level, even in active young men, the consumption of low levels of alcohol may be beneficial only if waist-to-hip ratio is maintained within the healthful range by achieving an appropriate balance of physical activity and macronutrient intake.

Distinct lipid/lipoprotein profiles and hormonal responsiveness in nine ethnic groups of postmenopausal Asian women: the Pan-Asia Menopause (PAM) study.

PubMed

Taechakraichana, N; Holinka, C F; Haines, C J; Subramaniam, R; Tian, X W; Ausmanas, M K

2007-06-01

Lipid/lipoprotein profiles, among other factors, are associated with risk of cardiovascular disease. Because cardiovascular disease varies in Asian countries, we hypothesized that lipid profiles differ in ethnic groups of postmenopausal Asian women. To add to the limited body of information currently available, we also investigated the effects of estrogen/progestin therapy on lipid/lipoprotein profiles in postmenopausal Asian women. The Pan-Asia Menopause (PAM) study was a prospective, randomized, double-blind clinical trial evaluating 1028 postmenopausal women at 22 investigational centers in 11 Asian countries/territories. Subjects were randomly assigned to one of three doses of continuous combined conjugated estrogens (CE)/medroxyprogesterone acetate (MPA): CE/MPA (in mg/day) = 0.625/2.5, 0.45/1.5 or 0.3/1.5. The treatment period, following baseline evaluations, consisted of six continuous 28-day cycles. Analysis of lipid profiles was a secondary objective of the PAM study. Total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), very low density cholesterol (VLDC-C), triglycerides and lipoprotein(a) were analyzed at a central laboratory by state-of-the-art methods. Mean concentrations of total cholesterol, LDL-C, VLDL-C and triglycerides differed significantly among the nine ethnic groups of postmenopausal women. This difference was independent of body mass index and age, two factors that also influenced lipid/lipoprotein profiles. Mean HDL-C concentrations also differed, but this difference was influenced by body mass index in a weak interaction. All three doses of CE/MPA significantly lowered total cholesterol. Treatment with the high and middle doses significantly lowered LDL-C, and increased HDL-C, VLDL-C and triglycerides. The high dose produced a significant decrease in lipoprotein(a). The different lipid/lipoprotein profiles in the nine ethnic groups of postmenopausal Asian women evaluated here suggest a relationship to differences in the prevalence of cardiovascular disease reported for different regions in Asia. However, the reported prevalence data on cardiovascular disease morbidity and mortality in the regions corresponding to the nine ethnic groups are insufficient to allow qualitative comparisons with the lipid profiles shown in our study. The lipid/lipoprotein changes in response to estrogen/progestin therapy observed here are consistent with those reported for Western women.

Correlation of Serum Lipoprotein Ratios with Insulin Resistance in Infertile Women with Polycystic Ovarian Syndrome: A Case Control Study.

PubMed

Ghaffarzad, Aisa; Amani, Reza; Mehrzad Sadaghiani, Mahzad; Darabi, Masoud; Cheraghian, Bahman

2016-01-01

Dyslipidemia and insulin resistance (IR), occurring in most infertile women with polycystic ovarian syndrome (PCOS), increase the risk of cardiovascular disease (CVD) and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES) criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu), insulin and lipid profile levels [triglycerides (TGs), total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C)] were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) were calculated. IR was also calculated using homeostasis model assessment (HOMA)-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Characteristics (ROC) curve analysis using the area under curve (AUC). Waist circumference (WC), insulin levels, HOMA-IR, TG levels, and all lipoprotein ratios were significantly higher, while HDL-C was lower in PCOS group as compared to healthy controls. All lipoprotein ratios, TG levels, and WC are significantly correlated with insulin levels and HOMA-IR. Among lipoprotein ratios, the highest AUC of the ROC belonged to TG/HDL-C ratio with sensitivity of 63.6% and specificity of 84.4% (TG/HDL-C>3.19) as a marker of IR in infertile PCOS women. Lipoprotein ratios, particularly TG/HDL-C, are directly correlated with insulin levels and can be used as a marker of IR (HOMA-IR) in infertile PCOS patients.

Edaravone attenuates monocyte adhesion to endothelial cells induced by oxidized low-density lipoprotein.

PubMed

Li, Zhijuan; Cheng, Jianxin; Wang, Liping

2015-10-30

Oxidized low-density lipoprotein (oxLDL) plays a vital role in recruitment of monocytes to endothelial cells, which is important during early stages of atherosclerosis development. Edaravone, a potent and novel scavenger of free radicals inhibiting hydroxyl radicals, has been clinically used to reduce the neuronal damage following ischemic stroke. In the present study, Edaravone was revealed to markedly reduce oxLDL-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). The inhibitory mechanism of Edaravone was associated with suppression of the chemokine MCP-1 and adhesion molecule VCAM-1 and ICAM-1 expression. In addition, luciferase reporter assay results revealed that administration of Edaravone attenuated the increase in NF-κB transcriptional activity induced by oxLDL. Notably, it's also shown that Edaravone treatment blocked oxLDL induced p65 nuclear translocation in HUVECs. Results indicate that Edaravone negatively regulates endothelial inflammation. Copyright © 2015. Published by Elsevier Inc.

Induction of protein oxidation in human low density lipoprotein by the photosensitive organic hydroperoxide, N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)-1,4,5,8-naphthalene-tetra-carb oxylic- diimide.

PubMed

Matsugo, S; Yan, L J; Han, D; Packer, L

1995-01-05

We have developed a new molecular probe, N,N'-bis(2-hydroxyperoxy-2-methyoxyethyl)-1,4,5,8-naphthalen e-tetra-carboxylic- diimide (NP-III), that specifically generates hydroxyl radical upon irradiation with longer wavelength ultraviolet light (UVA). Hydroxyl radicals are generated only upon irradiation, thus NP-III is a new controllable hydroxyl radical source. Apolipoprotein (apo-B) of human low density lipoprotein (LDL), and bovine serum alubumin (BSA), were irradiated with UVA in the presence of NP-III and their oxidation was evaluated by two independent methods: assay of protein carbonyl groups and gel electrophoresis. NP-III oxidized apo-B and BSA in a time- and concentration-dependent manner. The results demonstrate that NP-III is a controllable, precise, and potentially tagetable source of hydroxyl radicals with which to induce protein oxidation.

Lipid Lowering with Soluble Dietary Fiber.

PubMed

Surampudi, Prasanth; Enkhmaa, Byambaa; Anuurad, Erdembileg; Berglund, Lars

2016-12-01

Consumption of dietary soluble fibers has been associated with health benefits such as reduced lipid levels, lower blood pressure, improved blood glucose control, weight loss, improved immune function, and reduced inflammation. Many of these health benefits relate to a reduced risk of developing cardiovascular disease. In this paper, we have reviewed recent studies on the hypocholesterolemic effects of dietary soluble fibers as well as fiber-rich foods. Findings include the following: (a) consumption of water-soluble, viscous-forming fibers can reduce total and low-density lipoprotein cholesterol levels by about 5-10 %; (b) minimal changes of high-density lipoprotein cholesterol or triglyceride levels were observed; (c) cholesterol-lowering properties of soluble fibers depend on their physical and chemical properties; and (d) medium to high molecular weight fibers are more effective in reducing lipid levels. Hypocholesterolemic benefits were also observed with some fiber-rich foods, such as whole oats, whole barley, legumes, peas, beans, flax seeds, apples, and citrus foods.

The association of very-low-density lipoprotein with ankle-brachial index in peritoneal dialysis patients with controlled serum low-density lipoprotein cholesterol level

PubMed Central

2013-01-01

Background Peripheral artery disease (PAD) represents atherosclerotic disease and is a risk factor for death in peritoneal dialysis (PD) patients, who tend to show an atherogenic lipid profile. In this study, we investigated the relationship between lipid profile and ankle-brachial index (ABI) as an index of atherosclerosis in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level. Methods Thirty-five PD patients, whose serum LDL cholesterol level was controlled at less than 120mg/dl, were enrolled in this cross-sectional study in Japan. The proportions of cholesterol level to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions and the mean size of lipoprotein particles were measured using an improved method, namely, high-performance gel permeation chromatography. Multivariate linear regression analysis was adjusted for diabetes mellitus and cardiovascular and/or cerebrovascular diseases. Results The mean (standard deviation) age was 61.6 (10.5) years; PD vintage, 38.5 (28.1) months; ABI, 1.07 (0.22). A low ABI (0.9 or lower) was observed in 7 patients (low-ABI group). The low-ABI group showed significantly higher cholesterol proportions in the chylomicron fraction and large very-low-density lipoproteins (VLDLs) (Fractions 3–5) than the high-ABI group (ABI>0.9). Adjusted multivariate linear regression analysis showed that ABI was negatively associated with serum VLDL cholesterol level (parameter estimate=-0.00566, p=0.0074); the cholesterol proportions in large VLDLs (Fraction 4, parameter estimate=-3.82, p=0.038; Fraction 5, parameter estimate=-3.62, p=0.0039) and medium VLDL (Fraction 6, parameter estimate=-3.25, p=0.014); and the size of VLDL particles (parameter estimate=-0.0352, p=0.032). Conclusions This study showed that the characteristics of VLDL particles were associated with ABI among PD patients. Lowering serum VLDL level may be an effective therapy against atherosclerosis in PD patients after the control of serum LDL cholesterol level. PMID:24093487

Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

PubMed

Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

2017-06-01

Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p < 0.001). High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy, i.e. small low-density lipoproteins decreased whereas larger ones increased, and larger high-density lipoproteins decreased whereas smaller ones increased. The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies. These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study).

PubMed

Ballantyne, Christie M; Bays, Harold E; Kastelein, John J; Stein, Evan; Isaacsohn, Jonathan L; Braeckman, Rene A; Soni, Paresh N

2012-10-01

AMR101 is an ω-3 fatty acid agent containing ≥96% pure icosapent-ethyl, the ethyl ester of eicosapentaenoic acid. The efficacy and safety of AMR101 were evaluated in this phase 3, multicenter, placebo-controlled, randomized, double-blinded, 12-week clinical trial (ANCHOR) in high-risk statin-treated patients with residually high triglyceride (TG) levels (≥200 and <500 mg/dl) despite low-density lipoprotein (LDL) cholesterol control (≥40 and <100 mg/dl). Patients (n = 702) on a stable diet were randomized to AMR101 4 or 2 g/day or placebo. The primary end point was median percent change in TG levels from baseline versus placebo at 12 weeks. AMR101 4 and 2 g/day significantly decreased TG levels by 21.5% (p <0.0001) and 10.1% (p = 0.0005), respectively, and non-high-density lipoprotein (non-HDL) cholesterol by 13.6% (p <0.0001) and 5.5% (p = 0.0054), respectively. AMR101 4 g/day produced greater TG and non-HDL cholesterol decreases in patients with higher-efficacy statin regimens and greater TG decreases in patients with higher baseline TG levels. AMR101 4 g/day decreased LDL cholesterol by 6.2% (p = 0.0067) and decreased apolipoprotein B (9.3%), total cholesterol (12.0%), very-low-density lipoprotein cholesterol (24.4%), lipoprotein-associated phospholipase A(2) (19.0%), and high-sensitivity C-reactive protein (22.0%) versus placebo (p <0.001 for all comparisons). AMR101 was generally well tolerated, with safety profiles similar to placebo. In conclusion, AMR101 4 g/day significantly decreased median placebo-adjusted TG, non-HDL cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, lipoprotein-associated phospholipase A(2), and high-sensitivity C-reactive protein in statin-treated patients with residual TG elevations. Copyright © 2012 Elsevier Inc. All rights reserved.

ISIS 301012 gene therapy for hypercholesterolemia: sense, antisense, or nonsense?

PubMed

Ito, Matthew K

2007-10-01

To present an overview of antisense technology and to review and assess available literature on the chemistry, pharmacology, pharmacokinetics, drug interactions, preclinical and clinical studies, dosing, and adverse events of ISIS 301012 in the treatment of hyperlipidemia. PubMed database searches were conducted from 1966 to May 2007 using the search terms ISIS 301012, antisense, oligonucleotide, hypercholesterolemia, hyperlipidemia, and apolipoprotein B. Bibliographies of relevant review articles and information from the manufacturer were reviewed for additional references. Available English-language literature, including abstracts, preclinical, and clinical trials, review articles, and scientific presentations were examined. Apolipoprotein B is an important structural protein on the surface of atherogenic lipoproteins such as remnant very-low-density lipoprotein and low-density lipoprotein and facilitates the clearance of these particles from the circulation by binding to the low-density lipoprotein receptor. Overproduction of apolipoprotein B or reduced receptor-mediated clearance of lipoproteins leads to elevated serum cholesterol levels and premature atherosclerosis. ISIS 301012 is an antisense oligonucleotide that inhibits apolipoprotein B production by binding directly to and reducing the expression of apolipoprotein B messenger RNA. In a clinical trial, ISIS 301012 50-400 mg administered weekly via subcutaneous injection for 4 weeks reduced apolipoprotein B by 14.3-47.4% and low-density lipoprotein cholesterol by 5.9-40% at 55 days. The most frequent adverse event was injection-site erythema that resolved spontaneously. Studies are ongoing to further define the safety, efficacy, and pharmacokinetics of ISIS 301012 as add-on therapy in patients with heterozygous and homozygous familial hypercholesterolemia. No pharmacokinetic interactions have been demonstrated with ezetimibe and simvastatin. ISIS 301012 is the first agent to enter clinical trials utilizing an antisense mechanism for reducing the production of apolipoprotein B. Further studies are needed to verify its safety, efficacy, and position of therapy in the dyslipidemic patient.

ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.

PubMed

Xiao, Hong-Bo; Wang, Ji-Ying; Sun, Zhi-Liang

2017-12-01

Previous investigations have shown that inflammation induces changes in lipid and lipoprotein metabolism, and increased expression of angiopoietin-like protein 3 (ANGPTL3) contributes to the development of dyslipidemia. Here we investigated whether there is a correlation between increased ANGPTL3 expression and dyslipidemia in mastitis mice. Thirty mice were divided into two groups: control group and Staphylococcus aureus (S. aureus)-induced mastitis mice group. Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; activity of myeloperoxidase (MPO); concentrations of plasma inflammation biomarkers [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)]; concentration of plasma ANGPTL3 protein; lipoprotein lipase (LPL) activities in postheparin plasma; expressions of hepatic N-acetylgalactosaminyltransferase 2 (GALNT2), hepatic ANGPTL3 and adipose LPL were determined. The major results indicated specific pathological mammary tissue changes, elevated MPO activity, reduced GALNT2 mRNA expression, elevated ANGPTL3 mRNA and protein expression and reduced LPL mRNA and protein expression. In plasma samples the S.aureus infused mice displayed elevated ANGPTL3 protein concentration, TG, TC and LDL-C levels, and reduced postheparin LPL activities and HDL-C level. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Roles of the low density lipoprotein receptor and related receptors in inhibition of lipoprotein(a) internalization by proprotein convertase subtilisin/kexin type 9.

PubMed

Romagnuolo, Rocco; Scipione, Corey A; Marcovina, Santica M; Gemin, Matthew; Seidah, Nabil G; Boffa, Michael B; Koschinsky, Marlys L

2017-01-01

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor for cardiovascular disease. The mechanisms underlying Lp(a) clearance from plasma remain unclear, which is an obvious barrier to the development of therapies to specifically lower levels of this lipoprotein. Recently, it has been documented that monoclonal antibody inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) can lower plasma Lp(a) levels by 30%. Since PCSK9 acts primarily through the low density lipoprotein receptor (LDLR), this result is in conflict with the prevailing view that the LDLR does not participate in Lp(a) clearance. To support our recent findings in HepG2 cells that the LDLR can act as a bona fide receptor for Lp(a) whose effects are sensitive to PCSK9, we undertook a series of Lp(a) internalization experiments using different hepatic cells, with different variants of PCSK9, and with different members of the LDLR family. We found that PCSK9 decreased Lp(a) and/or apo(a) internalization by Huh7 human hepatoma cells and by primary mouse and human hepatocytes. Overexpression of human LDLR appeared to enhance apo(a)/Lp(a) internalization in both types of primary cells. Importantly, internalization of Lp(a) by LDLR-deficient mouse hepatocytes was not affected by PCSK9, but the effect of PCSK9 was restored upon overexpression of human LDLR. In HepG2 cells, Lp(a) internalization was decreased by gain-of-function mutants of PCSK9 more than by wild-type PCSK9, and a loss-of function variant had a reduced ability to influence Lp(a) internalization. Apo(a) internalization by HepG2 cells was not affected by apo(a) isoform size. Finally, we showed that very low density lipoprotein receptor (VLDLR), LDR-related protein (LRP)-8, and LRP-1 do not play a role in Lp(a) internalization or the effect of PCSK9 on Lp(a) internalization. Our findings are consistent with the idea that PCSK9 inhibits Lp(a) clearance through the LDLR, but do not exclude other effects of PCSK9 such as on Lp(a) biosynthesis.

Roles of the low density lipoprotein receptor and related receptors in inhibition of lipoprotein(a) internalization by proprotein convertase subtilisin/kexin type 9

PubMed Central

Marcovina, Santica M.; Gemin, Matthew; Seidah, Nabil G.; Boffa, Michael B.

2017-01-01

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor for cardiovascular disease. The mechanisms underlying Lp(a) clearance from plasma remain unclear, which is an obvious barrier to the development of therapies to specifically lower levels of this lipoprotein. Recently, it has been documented that monoclonal antibody inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) can lower plasma Lp(a) levels by 30%. Since PCSK9 acts primarily through the low density lipoprotein receptor (LDLR), this result is in conflict with the prevailing view that the LDLR does not participate in Lp(a) clearance. To support our recent findings in HepG2 cells that the LDLR can act as a bona fide receptor for Lp(a) whose effects are sensitive to PCSK9, we undertook a series of Lp(a) internalization experiments using different hepatic cells, with different variants of PCSK9, and with different members of the LDLR family. We found that PCSK9 decreased Lp(a) and/or apo(a) internalization by Huh7 human hepatoma cells and by primary mouse and human hepatocytes. Overexpression of human LDLR appeared to enhance apo(a)/Lp(a) internalization in both types of primary cells. Importantly, internalization of Lp(a) by LDLR-deficient mouse hepatocytes was not affected by PCSK9, but the effect of PCSK9 was restored upon overexpression of human LDLR. In HepG2 cells, Lp(a) internalization was decreased by gain-of-function mutants of PCSK9 more than by wild-type PCSK9, and a loss-of function variant had a reduced ability to influence Lp(a) internalization. Apo(a) internalization by HepG2 cells was not affected by apo(a) isoform size. Finally, we showed that very low density lipoprotein receptor (VLDLR), LDR-related protein (LRP)-8, and LRP-1 do not play a role in Lp(a) internalization or the effect of PCSK9 on Lp(a) internalization. Our findings are consistent with the idea that PCSK9 inhibits Lp(a) clearance through the LDLR, but do not exclude other effects of PCSK9 such as on Lp(a) biosynthesis. PMID:28750079

Mipomersen, an antisense apolipoprotein B synthesis inhibitor.

PubMed

Bell, Damon A; Hooper, Amanda J; Burnett, John R

2011-02-01

mipomersen is a second-generation antisense oligonucleotide (ASO) targeted to human apolipoprotein (apo) B-100, a large protein synthesized by the liver that plays a fundamental role in human lipoprotein metabolism. Mipomersen predominantly distributes to the liver and decreases the production of apoB-100, the primary structural protein of the atherogenic lipoproteins including low density lipoprotein (LDL), thereby reducing plasma LDL-cholesterol and apoB-100 concentrations. the mode of action, preclinical development and clinical trials of mipomersen, an antisense apoB synthesis inhibitor. The paper provides an understanding of the pharmacokinetic and pharmacodynamic characteristics of mipomersen and insight into its clinical efficacy and safety. In clinical trials, mipomersen produced dose-dependent and prolonged reductions in LDL-cholesterol and other apoB-containing lipoproteins, including lipoprotein (a) [Lp(a)] in healthy volunteers and in patients with mild to moderate hypercholesterolemia. Mipomersen has been shown to decrease apoB, LDL-cholesterol and Lp(a) in patients with heterozygous and homozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. mipomersen shows promise as an adjunctive agent by reducing apoB-containing lipoproteins in patients at high risk of atherosclerotic cardiovascular disease who are not at target or are intolerant of statins. Although the short-term efficacy and safety of mipomersen has been established, concern exists regarding the long-term potential for hepatic steatosis with this ASO.

Automated Processing of Plasma Samples for Lipoprotein Separation by Rate-Zonal Ultracentrifugation.

PubMed

Peters, Carl N; Evans, Iain E J

2016-12-01

Plasma lipoproteins are the primary means of lipid transport among tissues. Defining alterations in lipid metabolism is critical to our understanding of disease processes. However, lipoprotein measurement is limited to specialized centers. Preparation for ultracentrifugation involves the formation of complex density gradients that is both laborious and subject to handling errors. We created a fully automated device capable of forming the required gradient. The design has been made freely available for download by the authors. It is inexpensive relative to commercial density gradient formers, which generally create linear gradients unsuitable for rate-zonal ultracentrifugation. The design can easily be modified to suit user requirements and any potential future improvements. Evaluation of the device showed reliable peristaltic pump accuracy and precision for fluid delivery. We also demonstrate accurate fluid layering with reduced mixing at the gradient layers when compared to usual practice by experienced laboratory personnel. Reduction in layer mixing is of critical importance, as it is crucial for reliable lipoprotein separation. The automated device significantly reduces laboratory staff input and reduces the likelihood of error. Overall, this device creates a simple and effective solution to formation of complex density gradients. © 2015 Society for Laboratory Automation and Screening.

Inhibition of plasminogen activator inhibitor-1 binding to endocytosis receptors of the low-density-lipoprotein receptor family by a peptide isolated from a phage display library

PubMed Central

Jensen, Jan K.; Malmendal, Anders; Schiøtt, Birgit; Skeldal, Sune; Pedersen, Katrine E.; Celik, Leyla; Nielsen, Niels Chr.; Andreasen, Peter A.; Wind, Troels

2006-01-01

The functions of the serpin PAI-1 (plasminogen activator inhibitor-1) are based on molecular interactions with its target proteases uPA and tPA (urokinase-type and tissue-type plasminogen activator respectively), with vitronectin and with endocytosis receptors of the low-density-lipoprotein family. Understanding the significance of these interactions would be facilitated by the ability to block them individually. Using phage display, we have identified the disulfide-constrained peptide motif CFGWC with affinity for natural human PAI-1. The three-dimensional structure of a peptide containing this motif (DVPCFGWCQDA) was determined by liquid-state NMR spectroscopy. A binding site in the so-called flexible joint region of PAI-1 was suggested by molecular modelling and validated through binding studies with various competitors and site-directed mutagenesis of PAI-1. The peptide with an N-terminal biotin inhibited the binding of the uPA–PAI-1 complex to the endocytosis receptors low-density-lipoprotein-receptor-related protein 1A (LRP-1A) and very-low-density-lipoprotein receptor (VLDLR) in vitro and inhibited endocytosis of the uPA–PAI-1 complex in U937 cells. We conclude that the isolated peptide represents a novel approach to pharmacological interference with the functions of PAI-1 based on inhibition of one specific molecular interaction. PMID:16813566

Interaction of estradiol and high density lipoproteins on proliferation of the human breast cancer cell line MCF-7 adapted to grow in serum free conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jozan, S.; Faye, J.C.; Tournier, J.F.

1985-11-27

The responsiveness of the human mammary carcinoma cell line MCF-7 to estradiol and tamoxifen treatment has been studied in different culture conditions. Cells from exponentially growing cultures were compared with cells in their initial cycles after replating from confluent cultures (''confluent-log'' cells). It has been observed that estradiol stimulation of tritiated thymidine incorporation decreases with cell density and that ''confluent-log'' cells are estrogen unresponsive for a period of four cell cycles in serum-free medium conditions. On the other hand, growth of cells replated from exponentially growing, as well as from confluent cultures, can be inhibited by tamoxifen or a combinedmore » treatment with tamoxifen and the progestin levonorgestrel. This growth inhibitory effect can be rescued by estradiol when cells are replated from exponentially growing cultures. The growth inhibitory effect cannot be rescued by estradiol alone (10(-10) to 10(-8) M) when cells are replated from confluent cultures. In this condition, the addition of steroid depleted serum is necessary to reverse the state of estradiol unresponsiveness. Serum can be replaced by high density lipoproteins but not by low density lipoproteins or lipoprotein deficient serum. The present data show that estradiol and HDL interact in the control of MCF-7 cell proliferation.« less

Liver-specific expression of carboxylesterase 1g/esterase-x reduces hepatic steatosis, counteracts dyslipidemia and improves insulin signaling.

PubMed

Bahitham, Wesam; Watts, Russell; Nelson, Randal; Lian, Jihong; Lehner, Richard

2016-05-01

Ces1g/Es-x deficiency in mice results in weight gain, insulin resistance, fatty liver and hyperlipidemia through upregulation of de novo lipogenesis and oversecretion of triacylglycerol (TG)-rich lipoproteins. Here, we show that restoration of Ces1g/Es-x expression only in the liver significantly reduced hepatic TG concentration accompanied by decreased size of lipid droplets, reduced secretion of very low-density lipoproteins and improved insulin-mediated signal transduction in the liver. Collectively, these results demonstrate that hepatic Ces1g/Es-x plays a critical role in limiting hepatic steatosis, very low-density lipoprotein assembly and in augmenting insulin sensitivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of obesity and body fat distribution on cardiovascular risk factors in Hong Kong Chinese.

PubMed

Thomas, G Neil; Ho, Sai-Yin; Lam, Karen S L; Janus, Edward D; Hedley, Anthony J; Lam, Tai Hing

2004-11-01

Body fat distribution has been reported to differentially contribute to the development of cardiovascular risk. We report the relative associations between general and central obesity and risk factors in 2893 Chinese subjects recruited from the Hong Kong population. Anthropometric parameters [waist circumference (WC) and BMI], surrogate measures of insulin resistance (fasting plasma glucose and insulin, oral glucose tolerance test, 2 hours glucose and insulin), fasting lipids (total, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides) and systolic and diastolic blood pressure were measured. General obesity was classified as BMI > or =25.0 kg/m(2) and central obesity as a WC > or =80 or > or =90 cm in women and men, respectively. A total of 39.2% of the population was found to be obese. Obesity per se increased the levels of the risk factors, but central adiposity contributed to a greater extent to adverse high-density lipoprotein-cholesterol, triglyceride, and insulin resistance levels. There was a continuous relationship between increasing obesity, both general and central, and cardiovascular risk, with lowest risk associated with the lowest indices of obesity. In the 1759 nonobese subjects divided into quartiles of BMI or WC, the levels of the cardiovascular risk factors still significantly increased with increasing quartiles of adiposity. Central adiposity appears to contribute to a greater extent than general adiposity to the development of cardiovascular risk in this population. The relationship between obesity parameters and risk is a continuum, with risk factors significantly increasing even at levels usually considered nonobese. These observations support the proposed redefinition of overweight and obesity in Asian populations using lower cut-off points.

A Genomic DNA Reporter Screen Identifies Squalene Synthase Inhibitors That Act Cooperatively with Statins to Upregulate the Low-Density Lipoprotein Receptor

PubMed Central

Kerr, Alastair G.; Tam, Lawrence C. S.; Hale, Ashley B.; Cioroch, Milena; Douglas, Gillian; Agkatsev, Sarina; Hibbitt, Olivia; Mason, Joseph; Holt-Martyn, James; Bataille, Carole J. R.; Wynne, Graham M.; Channon, Keith M.; Russell, Angela J.

2017-01-01

Hypercholesterolemia remains one of the leading risk factors for the development of cardiovascular disease. Many large double-blind studies have demonstrated that lowering low-density lipoprotein (LDL) cholesterol using a statin can reduce the risk of having a cardiovascular event by approximately 30%. However, despite the success of statins, some patient populations are unable to lower their LDL cholesterol to meet the targeted lipid levels, due to compliance or potency issues. This is especially true for patients with heterozygous familial hypercholesterolemia who may require additional upregulation of the low-density lipoprotein receptor (LDLR) to reduce LDL cholesterol levels below those achievable with maximal dosing of statins. Here we identify a series of small molecules from a genomic DNA reporter screen that upregulate the LDLR in mouse and human liver cell lines at nanomolar potencies (EC50 = 39 nM). Structure-activity relationship studies carried out on the lead compound, OX03771 [(E)-N,N-dimethyl-3-(4-styrylphenoxy)propan-1-amine], led to the identification of compound OX03050 [(E)-3-(4-styrylphenoxy)propan-1-ol], which had similar potency (EC50 = 26 nM) but a much-improved pharmacokinetic profile and showed in vivo efficacy. Compounds OX03050 and OX03771 were found to inhibit squalene synthase, the first committed step in cholesterol biosynthesis. These squalene synthase inhibitors were shown to act cooperatively with statins to increase LDLR expression in vitro. Overall, we demonstrated here a novel series of small molecules with the potential to be further developed to treat patients either alone or in combination with statins. PMID:28360334

Seasonal mercury exposure and oxidant-antioxidant status of James Bay sport fishermen.

PubMed

Bélanger, Marie-Claire; Mirault, Marc-Edouard; Dewailly, Eric; Plante, Michel; Berthiaume, Line; Noël, Micheline; Julien, Pierre

2008-05-01

The effects of a moderate seasonal exposure to methylmercury on plasma low-density lipoprotein (LDL) oxidation and cardiovascular risk indices are not known. The objective of the study was to assess the effects of a seasonal exposure to mercury at similar dose reported to increase cardiovascular risk through fish consumption. Effects on lipoprotein cholesterol and fatty acid profiles, LDL oxidation, and blood oxidant-antioxidant balance were to be assessed in sport fishermen presenting normal blood selenium and omega-3 fatty acid contents. Thirty-one healthy James Bay sport fishermen were assessed for within-subject longitudinal seasonal variations in hair and blood mercury, plasma oxidized LDL, lipophilic antioxidants, homocysteine, blood selenium, and glutathione peroxidase and reductase activities determined before and after the fishing season and compared by matched-pair tests. Hair mercury doubled during the fishing season (2.8+/-0.4 microg/g, P<.0001). Baseline blood selenium, homocysteine, and erythrocyte fatty acid profiles did not change. Plasma high-density lipoprotein cholesterol increased (+5%, P=.05), whereas very low-density lipoprotein cholesterol and oxidized LDL decreased (-8%, P=.05; -18%, P=.008). Blood glutathione peroxidase (+9.7%, P=.001), glutathione reductase (+7.2%, P<.0001), and total glutathione (+45% P<.0001) increased during the fishing season. Plasma total coenzyme Q10 (+13%, P=.02), ubiquinone-10 (+67%, P=.03), and beta-carotene (+46%, P=.01) also increased, whereas vitamin E status was unaffected. Pairwise correlations revealed no association between mercury exposure and any of the biomarkers investigated. In contrast, strong predictors of cardiovascular risk such as high-density lipoprotein cholesterol, oxidized LDL, and glutathione peroxidase improved during the fishing season despite elevated methylmercury exposure. The beneficial effects of seasonal fishing activity and fish consumption on cardiovascular health may suppress detrimental effects of concomitant moderate methylmercury exposure.

APOL1 nephropathy risk variants are associated with altered high-density lipoprotein profiles in African Americans.

PubMed

Gutiérrez, Orlando M; Judd, Suzanne E; Irvin, Marguerite R; Zhi, Degui; Limdi, Nita; Palmer, Nicholette D; Rich, Stephen S; Sale, Michèle M; Freedman, Barry I

2016-04-01

Two independent coding variants in the apolipoprotein L1 gene (APOL1), G1 and G2, strongly associate with nephropathy in African Americans; associations with cardiovascular disease are more controversial. Although APOL1 binds plasma high-density lipoproteins (HDLs), data on APOL1 risk variant associations with HDL subfractions are sparse. Two APOL1 G1 single nucleotide polymorphisms and the G2 insertion/deletion polymorphism were genotyped in 2010 Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study participants with nuclear magnetic resonance spectroscopy-based lipoprotein subfraction measurements. Linear regression was used to model associations between numbers of APOL1 G1/G2 risk variants and HDL subfractions, adjusting for demographic, clinical and ancestral covariates. Female sex and higher percentage of African ancestry were positively associated with the number of APOL1 G1/G2 risk alleles. In the unadjusted analysis, mean (standard error) small HDL concentrations (μmol/L) for participants with zero, one and two G1/G2 risk alleles were 19.0 (0.2), 19.7 (0.2) and 19.9 (0.4), respectively (P = 0.02). Adjustment for age, sex, diabetes and African ancestry did not change the results but strengthened the statistical significance (P = 0.004). No significant differences in large or medium HDL, very low-density lipoprotein or low-density lipoprotein particle concentrations were observed by APOL1 genotype. Greater numbers of APOL1 G1/G2 risk alleles were associated with higher small HDL particle concentrations in African Americans. These results may suggest novel areas of investigation to uncover reasons for the association between APOL1 risk variants with adverse outcomes in African Americans. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

APOL1 nephropathy risk variants are associated with altered high-density lipoprotein profiles in African Americans

PubMed Central

Gutiérrez, Orlando M.; Judd, Suzanne E.; Irvin, Marguerite R.; Zhi, Degui; Limdi, Nita; Palmer, Nicholette D.; Rich, Stephen S.; Sale, Michèle M.; Freedman, Barry I.

2016-01-01

Background Two independent coding variants in the apolipoprotein L1 gene (APOL1), G1 and G2, strongly associate with nephropathy in African Americans; associations with cardiovascular disease are more controversial. Although APOL1 binds plasma high-density lipoproteins (HDLs), data on APOL1 risk variant associations with HDL subfractions are sparse. Methods Two APOL1 G1 single nucleotide polymorphisms and the G2 insertion/deletion polymorphism were genotyped in 2010 Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study participants with nuclear magnetic resonance spectroscopy-based lipoprotein subfraction measurements. Linear regression was used to model associations between numbers of APOL1 G1/G2 risk variants and HDL subfractions, adjusting for demographic, clinical and ancestral covariates. Results Female sex and higher percentage of African ancestry were positively associated with the number of APOL1 G1/G2 risk alleles. In the unadjusted analysis, mean (standard error) small HDL concentrations (μmol/L) for participants with zero, one and two G1/G2 risk alleles were 19.0 (0.2), 19.7 (0.2) and 19.9 (0.4), respectively (P = 0.02). Adjustment for age, sex, diabetes and African ancestry did not change the results but strengthened the statistical significance (P = 0.004). No significant differences in large or medium HDL, very low-density lipoprotein or low-density lipoprotein particle concentrations were observed by APOL1 genotype. Conclusions Greater numbers of APOL1 G1/G2 risk alleles were associated with higher small HDL particle concentrations in African Americans. These results may suggest novel areas of investigation to uncover reasons for the association between APOL1 risk variants with adverse outcomes in African Americans. PMID:26152403

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

PubMed

Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

2017-11-13

The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly correlated with BMI (r = 0.56, P = 0.04), and hub genes of KCNN1 and AQP10 were differentially expressed. We identified significant genes and specific modules potentially related to BMI based on the gene expression profile data of monozygotic twins. The findings may help further elucidate the underlying mechanisms of obesity development and provide novel insights to research potential gene biomarkers and signaling pathways for obesity treatment. Further analysis and validation of the findings reported here are important and necessary when more sample size is acquired.

[Lack of association between the S447X variant of the lipoprotein lipase gene and plasma lipids. A preliminary study].

PubMed

Zambrano Morales, Mariana; Fernández Salgado, Erika; Balzán Urdaneta, Ligia; Labastidas, Neila; Aranguren-Méndez, José; Connell, Lissette; Molero Paredes, Tania; Rojas, Alicia; Panunzio, Amelia

2014-06-01

The increase in lipid plasma values is an important cardiovascular risk factor. Lipoprotein lipase (LPL) plays an important role in the lipoprotein metabolism and metabolic and genetic factors may influence its levels and functions. The S447X variant of the lipoprotein lipase gene is associated with changes in plasma lipids in different populations. The objective of this research was to analyze the S447X variant of the LPL gene and its relation with plasma lipids of individuals in Zulia state, Venezuela. With this purpose, we studied 75 individuals (34 men and 41 women) between 20 and 60 years of age. Each subject had a medical history which included family history, anthropometric characteristics, nutritional status evaluation and biochemical tests. Genomic DNA was extracted for the molecular study and the polymerase chain reaction was used, followed by enzyme digestion, for restriction fragments length polymorphisms using the Hinf I enzyme. The individuals studied had normal levels of blood glucose, triglycerides, total cholesterol and low density lipoproteins (LDL-C) and slightly decreased levels of high density lipoproteins (HDL-C). The genotypic distribution of the LPL gene S447X variant in the studied population was 90.6% for the homozygous genotype SS447 and 9.4% for the heterozygote SX447. The genotype 447XX was not identified. The population was found in Hardy Weinberg genetic equilibrium. No association between the S447X polymorphism of lipoprotein lipase gene and plasma lipids was observed.

Lipid and lipoprotein changes in women following 6 months of exercise training in a worksite fitness program.

PubMed

Grandjean, P W; Oden, G L; Crouse, S F; Brown, J A; Green, J S

1996-03-01

It was the purpose of this investigation to examine the influence of a worksite aerobic training program on serum lipid and lipoproteins and cardiovascular fitness in female employees. Thirty-seven healthy but previously untrained, female employees (Ss) from Westinghouse Corporation, (College Station, Texas) volunteered for the study. Ss were randomly assigned to either an exercise group (Ex) (n = 20) or control group (C) (n = 17). Prior to training (PRE) and following training (POST), all Ss were measured for weight (WT), body composition (%FAT) and tested for maximal oxygen consumption (VO2 max). PRE and POST Lipid analysis included: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG). Following PRE testing, the Ex group aerobically trained by walking, jogging and/or cycling, at least 3 days per wk for 24 wks. Exercise training resulted in an improvement in VO2 max (p < 0.0006) and a 2 kg WT loss in Ex (p < 0.025) with no change in C. Both Ex and C Ss exhibited a loss in %-FAT (p < 0.0001), and a decrease in TC (p < 0.0001) and LDL-C (p < 0.0001). No differences were observed between groups or over the training period for VLDL-C or TG. Although HDL-C increased 6 mg/dl in the Ex group but not in C, this difference did not reach statistical significance (p < 0.0625). These results demonstrate that aerobic training by females in a worksite fitness program significantly improves cardiovascular fitness without altering lipids or lipoproteins.

A baseline metabolomic signature is associated with immunological CD4+ T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients.

PubMed

Rodríguez-Gallego, Esther; Gómez, Josep; Pacheco, Yolanda M; Peraire, Joaquim; Viladés, Consuelo; Beltrán-Debón, Raúl; Mallol, Roger; López-Dupla, Miguel; Veloso, Sergi; Alba, Verónica; Blanco, Julià; Cañellas, Nicolau; Rull, Anna; Leal, Manuel; Correig, Xavier; Domingo, Pere; Vidal, Francesc

2018-03-13

Poor immunological recovery in treated HIV-infected patients is associated with greater morbidity and mortality. To date, predictive biomarkers of this incomplete immune reconstitution have not been established. We aimed to identify a baseline metabolomic signature associated with a poor immunological recovery after antiretroviral therapy (ART) to envisage the underlying mechanistic pathways that influence the treatment response. This was a multicentre, prospective cohort study in ART-naive and a pre-ART low nadir (<200 cells/μl) HIV-infected patients (n = 64). We obtained clinical data and metabolomic profiles for each individual, in which low molecular weight metabolites, lipids and lipoproteins (including particle concentrations and sizes) were measured by NMR spectroscopy. Immunological recovery was defined as reaching CD4 T-cell count at least 250 cells/μl after 36 months of virologically successful ART. We used univariate comparisons, Random Forest test and receiver-operating characteristic curves to identify and evaluate the predictive factors of immunological recovery after treatment. HIV-infected patients with a baseline metabolic pattern characterized by high levels of large high density lipoprotein (HDL) particles, HDL cholesterol and larger sizes of low density lipoprotein particles had a better immunological recovery after treatment. Conversely, patients with high ratios of non-HDL lipoprotein particles did not experience this full recovery. Medium very-low-density lipoprotein particles and glucose increased the classification power of the multivariate model despite not showing any significant differences between the two groups. In HIV-infected patients, a baseline healthier metabolomic profile is related to a better response to ART where the lipoprotein profile, mainly large HDL particles, may play a key role.

Loci for CETP, LPL, LIPC, and APOC3 affect plasma lipoprotein size and sub-population distribution in Hispanic and non-Hispanic white subjects: the Columbia University BioMarkers Study.

PubMed

Humphries, S E; Berglund, L; Isasi, C R; Otvos, J D; Kaluski, D; Deckelbaum, R J; Shea, S; Talmud, P J

2002-08-01

The effect of genetic variation on plasma lipoproteins and their subfraction distribution was examined. Forty Hispanic men and 223 women and 42 non-Hispanic white men and 53 women participated in the study. Genotypes for cholesteryl ester transfer protein (CETP TaqIB), hepatic lipase (LIPC -480 C > T), lipoprotein lipase (LPL S447X), and apolipoprotein CIII (APOC3--455T > C) were determined by polymerase chain reaction. Lipoprotein particle size distribution was determined by nuclear magnetic resonance. For all but APOC3, genotype effects were homogeneous in the ethnic/racial groups and men and women. Effects were seen primarily in the women. Compared to women carriers of the common CETP B1 allele, B2B2 women had significantly higher plasma levels of high-density lipoprotein cholesterol (HDL-C) (16.4.0%, p = 0.001), reflected in the level of larger HDL particles (21.9%, p = 0.001), and larger mean particle size of HDL (2.3%, p = 0.01) and low-density lipoproteins (LDL) (1.3%, p = 0.02). Compared to LPL 447S homozygous women carriers of the LPL 447X allele had significantly lower levels of very-low-density lipoprotein-triglyceride (VLDL-TG) (21.0%, p = 0.02). For APOC3, there was significant gender:genotype interaction with the genotype differences seen only in the men. Compared to men homozygous for the -455T allele, carriers of -455C had higher levels of VLDL-TG (71.4%, p = 0.0001), reflected in a larger mean VLDL particle size (13.7%, p = 0.009). LIPC genotype was not associated with significant effects on any of these traits. These data confirm the role of genetic variants of CETP, LPL and APOC3 in determining the relationship between VLDL, LDL and HDL particles.

Lipid Oxidation in Carriers of Lecithin:Cholesterol Acyltransferase Gene Mutations

PubMed Central

Holleboom, Adriaan G.; Daniil, Georgios; Fu, Xiaoming; Zhang, Renliang; Hovingh, G. Kees; Schimmel, Alinda W.; Kastelein, John J.P.; Stroes, Erik S.G.; Witztum, Joseph L.; Hutten, Barbara A.; Tsimikas, Sotirios; Hazen, Stanley L.; Chroni, Angeliki; Kuivenhoven, Jan Albert

2013-01-01

Objective Lecithin:cholesterol acyltransferase (LCAT) has been shown to play a role in the depletion of lipid oxidation products, but this has so far not been studied in humans. In this study, we investigated processes and parameters relevant to lipid oxidation in carriers of functional LCAT mutations. Methods and Results In 4 carriers of 2 mutant LCAT alleles, 63 heterozygotes, and 63 family controls, we measured activities of LCAT, paraoxonase 1, and platelet-activating factor-acetylhydrolase; levels of lysophosphatidylcholine molecular species, arachidonic and linoleic acids, and their oxidized derivatives; immunodetectable oxidized phospholipids on apolipoprotein (apo) B–containing and apo(a)-containing lipoproteins; IgM and IgG autoantibodies to malondialdehyde-low-density lipoprotein and IgG and IgM apoB-immune complexes; and the antioxidant capacity of high-density lipoprotein (HDL). In individuals with LCAT mutations, plasma LCAT activity, HDL cholesterol, apoA-I, arachidonic acid, and its oxidized derivatives, oxidized phospholipids on apo(a)-containing lipoproteins, HDL-associated platelet-activating factor-acetylhydrolase activity, and the antioxidative capacity of HDL were gene-dose–dependently decreased. Oxidized phospholipids on apoB-containing lipoproteins was increased in heterozygotes (17%; P<0.001) but not in carriers of 2 defective LCAT alleles. Conclusion Carriers of LCAT mutations present with significant reductions in LCAT activity, HDL cholesterol, apoA-I, platelet-activating factor-acetylhydrolase activity, and antioxidative potential of HDL, but this is not associated with parameters of increased lipid peroxidation; we did not observe significant changes in the oxidation products of arachidonic acid and linoleic acid, immunoreactive oxidized phospholipids on apo(a)-containing lipoproteins, and IgM and IgG autoantibodies against malondialdehyde-low-density lipoprotein. These data indicate that plasma LCAT activity, HDL-associated platelet-activating factor-acetylhydrolase activity, and HDL cholesterol may not influence the levels of plasma lipid oxidation products. PMID:23023370

Relationship between lipoprotein subfraction cholesterol and residual risk for cardiovascular outcomes: A post hoc analysis of the AIM-HIGH trial.

PubMed

Toth, Peter P; Jones, Steven R; Slee, April; Fleg, Jerome; Marcovina, Santica M; Lacy, Megan; McBride, Ruth; Boden, William E

2018-03-09

The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial failed to demonstrate incremental clinical benefit of extended-release niacin (ERN) in 3414 statin-treated patients with established cardiovascular (CV) disease who had low baseline levels of high-density lipoprotein cholesterol (HDL-C) as compared to placebo. A previous secondary analysis suggested that ERN provided outcome benefits in ERN-treated patients with high triglycerides (TGs; >200 mg/dL) and very low HDL-C (<32 mg/dL) at baseline. The current analysis sought to ascertain how changes in TG-enriched lipoproteins and HDL subfractions impact residual risk in the comparator treatment arms. We evaluated the relationship between niacin treatment, lipoproteins and their subfractions, and CV outcomes in a non-prespecified, post hoc analysis of the AIM-HIGH trial. Lipoprotein subfraction analysis was performed with zonal ultracentrifugation in 2457 AIM-HIGH participants at baseline and 1 year of treatment. Hazard ratios were estimated using Cox proportional hazards models for relationships between lipoproteins and the composite primary endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. Analyses were performed for the entire cohort and in participants with TGs > 200 mg/dL and HDL-C < 32 mg/dL. Apoprotein B-containing lipoproteins and their subfractions decreased significantly in both treatment arms but decreased more with ERN treatment. HDL-C and its subfractions increased significantly in both treatment groups, but more so in patients treated with ERN. For the entire study population, neither apoB- nor apoA1-containing lipoprotein subfractions predicted risk at baseline or at 1 year of follow-up. In the high TG and low HDL-C subgroup treated with placebo, changes at 1 year in HDL 2 -C, total cholesterol/HDL 2 -C, and non-HDL-C/HDL 2 -C may be associated with increased CV events, whereas in the ERN treatment arm, changes at 1 year in very low-density lipoprotein cholesterol and very low-density lipoprotein subfractions, total remnant lipoproteins, and various risk ratios may be associated with increased CV events, while HDL 2 -C may be associated with reduced risk. We provide hypothesis-generating findings that ERN may confer benefit in patients with coronary heart disease who have high TGs and low HDL by reducing serum levels of remnant lipoprotein cholesterol and increasing HDL 2 -C. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition

PubMed Central

Merzouk, H; Bouchenak, M; Loukidi, B; Madani, S; Prost, J; Belleville, J

2000-01-01

Aims—To determine the effects of fetal macrosomia related to maternal type 1 diabetes on the lipid transport system. Methods—Serum lipoprotein concentrations and composition and lecithin:cholesterol acyltransferase (LCAT) activity were investigated in macrosomic newborns (mean birth weight, 4650 g; SEM, 90) and their mothers with poorly controlled type 1 diabetes, in appropriate for gestational age newborns (mean birth weight, 3616 g; SEM, 68) and their mothers with well controlled type 1 diabetes, and macrosomic (mean birth weight, 4555 g; SEM, 86) or appropriate for gestational age (mean birth weight, 3290 g; SEM, 45) newborns and their healthy mothers. Results—In mothers with well controlled type 1 diabetes, serum lipids, apolipoproteins, and lipoproteins were comparable with those of healthy mothers. Similarly, in their infants, these parameters did not differ from those of appropriate for gestational age newborns. Serum triglyceride, very low density lipoprotein (VLDL), apolipoprotein B100 (apo B100), and high density lipoprotein (HDL) triglyceride concentrations were higher, whereas serum apo A-I and HDL3 concentrations were lower in mothers with diabetes and poor glycaemic control than in healthy mothers. Their macrosomic newborns had higher concentrations in all serum lipids and lipoproteins, with high apo A-I and apo B100 values compared with appropriate for gestational age newborns. In macrosomic infants of healthy mothers, there were no significant differences in lipoprotein profiles compared with those of appropriate for gestational age infants. LCAT activity was similar in both groups of mothers and newborns. Conclusion—Poorly controlled maternal type 1 diabetes and fetal macrosomia were associated with lipoprotein abnormalities. Macrosomic lipoprotein profiles related to poor metabolic control of type 1 diabetes appear to have implications for later metabolic diseases. Key Words: apolipoproteins • lipids • lipoproteins • lecithin:cholesterol acyltransferase • fetal macrosomia • maternal type 1 diabetes PMID:11265176

Greater adherence to a Mediterranean dietary pattern is associated with improved plasma lipid profile: the Aragon Health Workers Study cohort.

PubMed

Peñalvo, José L; Oliva, Belén; Sotos-Prieto, Mercedes; Uzhova, Irina; Moreno-Franco, Belén; León-Latre, Montserrat; Ordovás, José María

2015-04-01

There is wide recognition of the importance of healthy eating in cardiovascular health promotion. The purpose of this study was to identify the main dietary patterns among a Spanish population, and to determine their relationship with plasma lipid profiles. A cross-sectional analysis was conducted of data from 1290 participants of the Aragon Workers Health Study cohort. Standardized protocols were used to collect clinical and biochemistry data. Diet was assessed through a food frequency questionnaire, quantifying habitual intake over the past 12 months. The main dietary patterns were identified by factor analysis. The association between adherence to dietary patterns and plasma lipid levels was assessed by linear and logistic regression. Two dietary patterns were identified: a Mediterranean dietary pattern, high in vegetables, fruits, fish, white meat, nuts, and olive oil, and a Western dietary pattern, high in red meat, fast food, dairy, and cereals. Compared with the participants in the lowest quintile of adherence to the Western dietary pattern, those in the highest quintile had 4.6 mg/dL lower high-density lipoprotein cholesterol levels (P < .001), 8 mg/dL lower apolipoprotein A1 levels (P = .005) and a greater risk of having decreased high-density lipoprotein cholesterol (odds ratio = 3.19; 95% confidence interval, 1.36-7.5; P-trend = .03). Participants adhering to the Mediterranean dietary pattern had 3.3mg/dL higher high-density lipoprotein cholesterol levels (P < .001), and a ratio of triglycerides to high-density lipoprotein cholesterol that was 0.43 times lower (P = .043). Adherence to the Mediterranean dietary pattern is associated with improved lipid profile compared with a Western dietary pattern, which was associated with a lower odds of optimal high-density lipoprotein cholesterol levels in this population. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study.

PubMed

Sari, Ibrahim; Baltaci, Yasemin; Bagci, Cahit; Davutoglu, Vedat; Erel, Ozcan; Celik, Hakim; Ozer, Orhan; Aksoy, Nur; Aksoy, Mehmet

2010-04-01

Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters, endothelial function, inflammation, and oxidation in healthy young men living in a controlled environment. A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean age 22 y, range 21-24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements were performed at baseline and after each diet. Compared with the Mediterranean diet, the pistachio diet decreased glucose (P<0.001, -8.8+/-8.5%), low-density lipoprotein (P<0.001, -23.2+/-11.9%), total cholesterol (P<0.001, -21.2+/-9.9%), and triacylglycerol (P=0.008, -13.8+/-33.8%) significantly and high-density lipoprotein (P=0.069, -3.1+/-11.7%) non-significantly. Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly (P<0.001 for both). The pistachio diet significantly improved endothelium-dependent vasodilation (P=0.002, 30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and malondialdehyde and increased superoxide dismutase (P<0.001 for all), whereas there was no significant change in C-reactive protein and tumor necrosis factor-alpha levels. In this trial, we demonstrated that a pistachio diet improved blood glucose level, endothelial function, and some indices of inflammation and oxidative status in healthy young men. These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies. Copyright 2010. Published by Elsevier Inc.

Comparison of different statin therapy to change low-density lipoprotein cholesterol and high-density lipoprotein cholesterol level in Korean patients with and without diabetes.

PubMed

Khang, Ah Reum; Song, Young Shin; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Jang, Hak Chul; Choi, Sung Hee

2016-01-01

It is difficult to apply the proper intensity of statin for new treatment guidelines in clinical settings because of few data about the statin efficacy in Asians. We conducted a retrospective, observational study to estimate the percentage changes in lipid parameters and glucose induced by different statins. We analyzed 3854 patients including those with nondiabetes and diabetes treated at the outpatient clinic between 2003 and 2013 who were statin-naïve and maintained fixed-dose of statin for at least 18 months. Moderate- and low-intensity statin therapy was effective in reducing low-density lipoprotein cholesterol (LDL-C) to <100 mg/dL (70.3%, 83.0%, and 87.2% of diabetic patients in the low-, moderate-, and high-intensity therapy groups, respectively). The rapid decrease of LDL-C was observed in the first 8 months, and LDL-C-lowering effect was maintained throughout the observation period in even the low-intensity statin group. The effects of statins in elevating high-density lipoprotein cholesterol were similar in each statin groups, except the ezetimibe-simvastatin group (4.5 ± 2.1%) and high-dose atorvastatin groups (9.7 ± 3.3% and 8.7 ± 2.4% for 40 mg and 80 mg of atorvastatin/day, respectively). High-density lipoprotein cholesterol increased less and LDL-C decreased more in diabetes than in nondiabetes. There were no significant changes of fasting glucose after statin use in nondiabetic patients. Moderate- or low-intensity statin was effective enough in reaching National Cholesterol Education Program Adult Treatment Panel III LDL-C target goals in Koreans. Low-intensity statin showed around 30% LDL-C reduction from the baseline level in Koreans, which is comparable to moderate-intensity statin in new guideline. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Antioxidant/prooxidant effects of dietary non-flavonoid phenols on the Cu2+-induced oxidation of human low-density lipoprotein (LDL).

PubMed

Briante, Raffaella; Febbraio, Ferdinando; Nucci, Roberto

2004-11-01

A central role in the oxidative development of atherosclerotic lesions has been ascribed to the peroxidation of plasma low-density lipoprotein (LDL). Dietary supplementation with virgin olive oils increases the total plasma antioxidant status and the resistance of low-density lipoprotein to ex vivo oxidation. We have studied the effects of some dietary non-flavonoid phenols from Olea europaea L., both in purified form or in complex mixtures obtained by biotransformation of olive leaf extracts, on the LDL oxidation induced by Cu2+ ions. Cu2+-Induced LDL oxidation is inhibited by oleuropein and hydroxytyrosol in the initiation phase of the reaction at concentrations of phenols higher than that of Cu2+ ions. Interestingly, at lower concentration, both phenols anticipated the initiation process of LDL oxidation, thus exerting prooxidant capacities. Although similar effects are already described for flavonoids, such as quercetin, rutin, and apigenin, it is the first time that a prooxidant effect of dietary non-flavonoid phenols, such as oleuropein and hydroxytyrosol, on the LDL oxidation is reported. Our results show that a net effect of oleuropein and hydroxytyrosol on Cu2+-induced LDL peroxidation is determined by a balance of their pro- and antioxidant capacities. It is worth to underline that, during Cu2+-induced LDL oxidation in the presence of bioreactor eluates, we have evidence of a synergistic effect among phenolic compounds that enhance their antioxidant capacities so avoiding the prooxidant effects.

Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.

PubMed

Saïdi, Y; Sich, D; Camproux, A; Egloff, M; Federspiel, M C; Gautier, V; Raisonnier, A; Turpin, G; Beucler, I

1999-01-01

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.

Common variants associated with plasma triglycerides and risk for coronary artery disease.

PubMed

Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Goncalo R; Daly, Mark J; Neale, Benjamin M; Kathiresan, Sekar

2013-11-01

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Common variants associated with plasma triglycerides and risk for coronary artery disease

PubMed Central

Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L.; Ingelsson, Erik; Abecasis, Goncalo R.; Daly, Mark J.; Neale, Benjamin M.; Kathiresan, Sekar

2013-01-01

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10−8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

Lipoprotein lipase-dependent binding and uptake of low density lipoproteins by THP-1 monocytes and macrophages: possible involvement of lipid rafts.

PubMed

Makoveichuk, Elena; Castel, Susanna; Vilaró, Senen; Olivecrona, Gunilla

2004-11-08

Lipoprotein lipase (LPL) is produced by cells in the artery wall and can mediate binding of lipoproteins to cell surface heparan sulfate proteoglycans (HSPG), resulting in endocytosis (the bridging function). Active, dimeric LPL may dissociate to inactive monomers, the main form found in plasma. We have studied binding/internalization of human low density lipoprotein (LDL), mediated by bovine LPL, using THP-1 monocytes and macrophages. Uptake of (125)I-LDL was similar in monocytes and macrophages and was not affected by the LDL-receptor family antagonist receptor-associated protein (RAP) or by the phagocytosis inhibitor cytochalasin D. In contrast, uptake depended on HSPG and on membrane cholesterol. Incubation in the presence of dexamethasone increased the endogenous production of LPL by the cells and also increased LPL-mediated binding of LDL to the cell surfaces. Monomeric LPL was bound to the cells mostly in a heparin-resistant fashion. We conclude that the uptake of LDL mediated by LPL dimers is receptor-independent and involves cholesterol-enriched membrane areas (lipid rafts). Dimeric and monomeric LPL differ in their ability to mediate binding/uptake of LDL, probably due to different mechanisms for binding/internalization.

Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL.

PubMed

Caterer, Nigel R; Graversen, Jonas H; Jacobsen, Christian; Moestrup, Søren K; Sigurskjold, Bent W; Etzerodt, Michael; Thøgersen, Hans C

2002-11-01

Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1-110)]. Previous studies indicated that lipoprotein(a) non-covalently binds the N-terminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surface-exposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).

Prevention by lactic acid bacteria of the oxidation of human LDL.

PubMed

Terahara, M; Kurama, S; Takemoto, N

2001-08-01

Ether extracts of lactic acid bacteria were analyzed for prevention of the oxidation of erythrocyte membrane and human low-density lipoprotein in vivo. Streptococcus thermophilus 1131 and Lactobacillus delbrueckii subsp. bulgaricus 2038, yogurt starters, were chosen as test-strains, and ether extracts of these cultures were used as samples. Both strain 1131 and strain 2038 produced radical scavengers and inhibited oxidation of erythrocyte membranes and low-density lipoproteins. The antioxidative activity of strain 2038 was higher than that of strain 1131.

Development, Implementation, and Evaluation of a Health Promotion Program in a College Setting.

ERIC Educational Resources Information Center

Fisher, Shirley P.; Fisher, Michele M.

1995-01-01

An evaluation of a health promotion program for employees at a New Jersey state college assessed the physical fitness and exercise program with educational components. Comparisons of experimental and control subjects indicated significant differences on high density lipoprotein (HDL), total cholesterol/HDL ratio, triglycerides, and body weight in…

Genetic Alterations Affecting Cholesterol Metabolism and Human Fertility1

PubMed Central

DeAngelis, Anthony M.; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-01-01

ABSTRACT Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID:25122065

Pleiotropic Effect of Lipoprotein-Apheresis on the Soluble Form of Activated Leukocyte Cell Adhesion Molecule (sALCAM) in Familial Hypercholesterolaemia.

PubMed

von Bauer, Rüdiger; Oikonomou, Dimitrios; Sulaj, Alba; Kopf, Stefan; Fleming, Thomas; Rudofsky, Gottfried; Nawroth, Peter

2018-06-11

Atherosclerosis is an inflammatory disorder in which several converging immune responses modulate and induce lipid accumulation in macrophages. Activated leukocyte cell adhesion molecule (ALCAM) has been described as a structural homologue of HDL-receptor and functions as a pattern recognition receptor (PRR), while its soluble form sALCAM is involved in ALCAM-dependent and -independent immune mechanisms. The aim of this study was to investigate the effect of aggressive removal of low density lipoprotein-cholesterol (LDL-C) and lipoprotein(a) (Lp [a]) by lipoprotein-apheresis (LA) on sALCAM and blood viscosity as well as to evaluate its association with lipoproteins and serum markers of inflammation. © Georg Thieme Verlag KG Stuttgart · New York.

Preparation and Characterization of Stable α-Synuclein Lipoprotein Particles.

PubMed

Eichmann, Cédric; Campioni, Silvia; Kowal, Julia; Maslennikov, Innokentiy; Gerez, Juan; Liu, Xiaoxia; Verasdonck, Joeri; Nespovitaya, Nadezhda; Choe, Senyon; Meier, Beat H; Picotti, Paola; Rizo, Josep; Stahlberg, Henning; Riek, Roland

2016-04-15

Multiple neurodegenerative diseases are caused by the aggregation of the human α-Synuclein (α-Syn) protein. α-Syn possesses high structural plasticity and the capability of interacting with membranes. Both features are not only essential for its physiological function but also play a role in the aggregation process. Recently it has been proposed that α-Syn is able to form lipid-protein particles reminiscent of high-density lipoproteins. Here, we present a method to obtain a stable and homogeneous population of nanometer-sized particles composed of α-Syn and anionic phospholipids. These particles are called α-Syn lipoprotein (nano)particles to indicate their relationship to high-density lipoproteins formed by human apolipoproteins in vivo and of in vitro self-assembling phospholipid bilayer nanodiscs. Structural investigations of the α-Syn lipoprotein particles by circular dichroism (CD) and magic angle solid-state nuclear magnetic resonance (MAS SS-NMR) spectroscopy establish that α-Syn adopts a helical secondary structure within these particles. Based on cryo-electron microscopy (cryo-EM) and dynamic light scattering (DLS) α-Syn lipoprotein particles have a defined size with a diameter of ∼23 nm. Chemical cross-linking in combination with solution-state NMR and multiangle static light scattering (MALS) of α-Syn particles reveal a high-order protein-lipid entity composed of ∼8-10 α-Syn molecules. The close resemblance in size between cross-linked in vitro-derived α-Syn lipoprotein particles and a cross-linked species of endogenous α-Syn from SH-SY5Y human neuroblastoma cells indicates a potential functional relevance of α-Syn lipoprotein nanoparticles. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mipomersen is a promising therapy in the management of hypercholesterolemia: a meta-analysis of randomized controlled trials.

PubMed

Li, Na; Li, Qing; Tian, Xia-Qiu; Qian, Hai-Yan; Yang, Yue-Jin

2014-10-01

By inhibiting apolipoprotein B (ApoB) synthesis, mipomersen can significantly reduce ApoB-containing lipoproteins in hypercholesterolemic patients. This study sought to ascertain both the extent to which mipomersen can decrease ApoB-containing lipoproteins and the safety of mipomersen therapy. Studies were identified through PubMed, CENTRAL, Embase, Clinical Trials, reviews, and reference lists of relevant papers. The efficacy endpoints were the changes in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), ApoB, and lipoprotein (a) [Lp(a)]. The safety endpoints were the incidence of injection-site reactions, flu-like symptoms, and elevated transaminases. Six randomized controlled trials with 444 patients were included in the analysis. Compared with the placebo group, patients who received mipomersen therapy had a significant reduction in LDL-C (33.13%), as well as a reduction in non-HDL-C (31.70%), ApoB (33.27%), and LP(a) (26.34%). Mipomersen therapy was also associated with an obvious increase in injection-site reactions with an odds ratio (OR) of 14.15, flu-like symptoms with an OR of 2.07, and alanine aminotransferase levels ≥ 3 × the upper limit of normal with an OR of 11.21. Mipomersen therapy is effective for lowering ApoB-containing lipoproteins in patients with severe hypercholesterolemia. Future studies exploring how to minimize side effects of mipomersen therapy are needed.

Ocimum gratissmum aqueous extract reduces plasma lipid in hypercholesterol-fed hamsters

PubMed Central

Chao, Pei-Yu; Lin, James A.; Ting, Wei-Jen; Lee, Hsueh-Hui; Hsieh, Kuanghui; Chiu, Yung-Wei; Lai, Te-Jen; Hwang, Jin-Ming; Liu, Je-rYuh; Huang, Chih-Yang

2016-01-01

Objectives: Hyperlipidemia is a significant risk factor in the development of atherosclerosis and related diseases which are major health problem in many developed and developing countries that can lead to fatality due to the changes in lifestyle and dietary habits in this modern age. Methods: In the present study, the Ocimum gratissimum aqueous extract (OGE) was tested for the lowering effect on the serum lipid level of male hamsters on a high-fat (12%) and high-cholesterol (0.2%) diet (HFCD). Results: The results showed that the levels of serum high-density-lipoprotein-cholesterol (HDL-C) low-density-lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerols (TG) were increased in the HFCD group (113±11, 259±87, 629±175 and 625±262, respectively), as compared to the control normal diet group (51±8, 19±5, 77±16 and 101±44, respectively). When co-treated with various doses (10 and 20 mg/kg) of the OGE or rosuvastatin, the rats exhibited the restoration of normal serum LDL-C, TC, and TG levels. Conclusion: Therefore, we suggest that the Ocimum gratissimum aqueous extract may have the potential function of lowering serum lipid in rats. PMID:27877073

Antihyperlipidemic effect of Scoparia dulcis (sweet broomweed) in streptozotocin diabetic rats.

PubMed

Pari, Leelavinothan; Latha, Muniappan

2006-01-01

We have investigated Scoparia dulcis, an indigenous plant used in Ayurvedic medicine in India, for its possible antihyperlipidemic effect in rats with streptozotocin-induced experimental diabetes. Oral administration of an aqueous extract of S. dulcis plant (200 mg/kg of body weight) to streptozotocin diabetic rats for 6 weeks resulted in a significant reduction in blood glucose, serum and tissue cholesterol, triglycerides, free fatty acids, phospholipids, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity, and very low-density lipoprotein and low-density lipoprotein cholesterol levels. The decreased serum high-density lipoprotein cholesterol, anti-atherogenic index, and HMG-CoA reductase activity in diabetic rats were also reversed towards normalization after the treatment. Similarly, the administration of S. dulcis plant extract (SPEt) to normal animals resulted in a hypolipidemic effect. The effect was compared with glibenclamide (600 microg/kg of body weight). The results showed that SPEt had antihyperlipidemic action in normal and experimental diabetic rats in addition to its antidiabetic effect.

Management of dyslipidemia in women in the post-hormone therapy era.

PubMed

Mosca, Lori

2005-03-01

Cardiovascular disease (CVD) is the leading cause of death for women in the United States and is largely preventable. The American Heart Association has recently released evidence-based guidelines for the prevention of CVD in women; these include gender-specific recommendations for the management of dyslipidemia. This article reviews these recommendations and the evidence supporting them. This was a qualitative review of a systematic literature search related to lipid guidelines for women and discussion of rationale and evidence for new clinical recommendations. Lifestyle modifications are the cornerstone of lipid management. Substantial evidence from randomized clinical trials supports the use of low-density lipoprotein cholesterol-lowering therapy (primarily statins) in all high-risk women and the use of niacin or fibrates when high-density lipoprotein cholesterol is low or non-high-density lipoprotein cholesterol is elevated. Fewer data are available for women at lower or intermediate risk. Encouragement of lifestyle modification and appropriate use of lipid-altering therapy will have a substantial impact on reducing the burden of cardiovascular disease in women.

Prevalence of unrecognized dyslipidaemia in Dubai and Northern Emirates: a cross-sectional hospital based study.

PubMed

Vela, Barbara Karin; Alhessi, Alaaeldin Y; Popović, Marko; Al-Shaqra, Maryam A

2008-12-01

The aim of this study is to determine the prevalence of unrecognized dyslipidaemia and a specific correlation between lipid values and age, gender or ethnic origin in the study population. This retrospective cross-sectional study included 311 subjects who had their lipid profiles checked for the first time in a private hospital in Dubai in a six month - period. The analysis shows an increased prevalence of Low Density Lipoprotein (LDL) hypercholesterolemia with relatively higher Low Density Lipoprotein Cholesterol (LDL-c) values in male subjects (p < 0.016) as well as with the Middle East ethnic origin group (p < 0.025), while desirable High Density Lipoprotein (HDL-c) was found among female subjects (p = 0). The discordance between the percentages of elevated LDL-c and Total cholesterol (T-c) signifies the role of the LDL-c/non-HDL-c as the main surrogate for dyslipidaemia as a risk for atherosclerosis, and as a primary target of therapy.

Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo.

PubMed

Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; van den Hoff, Joerg

2004-11-01

Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [(18)F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo.

Peroxisome proliferator-activated receptor gamma co-activator 1 gene Gly482Ser polymorphism is associated with the response of low-density lipoprotein cholesterol concentrations to exercise training in elderly Japanese.

PubMed

Tobina, Takuro; Mori, Yukari; Doi, Yukiko; Nakayama, Fuki; Kiyonaga, Akira; Tanaka, Hiroaki

2017-09-01

Muscle peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1)α gene expression is influenced by the Gly482Ser gene polymorphism, which is a candidate genetic risk factor for diabetes mellitus and obesity. This study investigated the effects of PGC-1 gene Gly482Ser polymorphisms on alterations in glucose and lipid metabolism induced by exercise training. A 12-week intervention study was performed for 119 participants who were more than 65 years of age and completed exercise training at lactate threshold intensity. Total cholesterol and low-density lipoprotein cholesterol were significantly reduced in Gly/Gly but not in Gly/Ser and Ser/Ser participants after exercise. The Gly/Gly genotype of the PGC-1 gene Gly482Ser polymorphism influences the effects of moderate-intensity exercise training on low-density lipoprotein cholesterol and total cholesterol concentrations in older people.

Effect of air flow rate on the polyphenols content and antioxidant capacity of convective dried cactus pear cladodes (Opuntia ficus indica).

PubMed

Gallegos-Infante, José-Alberto; Rocha-Guzman, Nuria-Elizabeth; González-Laredo, Ruben-Francisco; Reynoso-Camacho, Rosalia; Medina-Torres, Luis; Cervantes-Cardozo, Veronica

2009-01-01

The interest in nopal has encouraged the use of dehydration; there are few studies about the effect of process parameters on the nopal polyphenol content and antioxidant activity. The objective of the present work was to evaluate the effect of air-drying flow rates on the amount and antioxidant capacity of extracts of Opuntia ficus indica cladodes. Nopal was dried at 45 degrees C and air flow rates of 3 and 5 m/sec. Samples were analyzed for moisture, total polyphenol, flavonoid, and flavonol contents, chain-breaking activity, inhibition of low-density lipoprotein and deoxyribose oxidation. Nopal drying at an air flow rate of 3 m/sec showed higher values of phenols, flavonoids and flavonols. The best value of low-density lipoprotein inhibition and deoxyribose was found at 1,000 microg/ml. The air flow rate affected the amount of polyphenols and the OH( . ) radical scavenging, but did not modify the chain-breaking activity and the low-density lipoprotein inhibition activity.

Regulation of PCSK9 by nutraceuticals.

PubMed

Momtazi, Amir Abbas; Banach, Maciej; Pirro, Matteo; Katsiki, Niki; Sahebkar, Amirhossein

2017-06-01

PCSK9 (proprotein convertase subtilisin kexin type 9) is a liver secretory enzyme that regulates plasma low-density lipoprotein (LDL) cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR) density on the surface of hepatocytes. Inhibition of PCSK9 using monoclonal antibodies can efficiently lower plasma LDL-C, non-high-density lipoprotein cholesterol and lipoprotein (a). PCSK9 inhibition is also an effective adjunct to statin therapy; however, the cost-effectiveness of currently available PCSK9 inhibitors is under question. Nutraceuticals offer a safe and cost-effective option for PCSK9 inhibition. Several nutraceuticals have been reported to modulate PCSK9 levels and exert LDL-lowering activity. Mechanistically, those nutraceuticals that inhibit PCSK9 through a SREBP (sterol-responsive element binding protein)-independent pathway can be more effective in lowering plasma LDL-C levels compared with those inhibiting PCSK9 through the SREBP pathway. The present review aims to collect available data on the nutraceuticals with PCSK9-inhibitory effect and the underlying mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Saturated fatty acids and risk of coronary heart disease: modulation by replacement nutrients.

PubMed

Siri-Tarino, Patty W; Sun, Qi; Hu, Frank B; Krauss, Ronald M

2010-11-01

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat.

Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

PubMed

Katz, Pamela M; Leiter, Lawrence A

2012-01-01

Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The saponin-rich fraction of a Gymnema sylvestre R. Br. aqueous leaf extract reduces cafeteria and high-fat diet-induced obesity.

PubMed

Reddy, Rama Manohar I; Latha, Pushpa B; Vijaya, Tartte; Rao, Dattatreya S

2012-01-01

We examined the antiobesity effect of a saponin-rich fraction of a Gymnema sylvestre R. Br. aqueous leaf extract (SGE) using cafeteria and high-fat diet-induced obese rats for a period of eight weeks. SGE was orally administered at a dose of 100 mg/kg body weight once a day to the treatment group. It significantly decreased the body weight, food consumption, visceral organs weight, and the levels of triglycerides, total cholesterol, low-density lipoproteins, very low-density lipoproteins, atherogenic index, glucose, and increased the levels of high-density lipoproteins. There was no significant difference with respect to all parameters of the study in case of normal (N) diet and N diet + SGE rats. In vitro, SGE inhibited the pancreatic lipase activity. The present study gave clear evidence that the SGE has a significant antiobese action, supporting its use in traditional medicine, and can be used as a substitute for synthetic drugs.

[Periodontal treatment for cardiovascular risk factors: a systematic review].

PubMed

Deng, Linkai; Li, Chunjie; Li, Qian; Zhang, Yukui; Zhao, Hongwei

2013-10-01

To evaluate the efficacy of periodontal treatment for the management of cardiovascular risk factors. Eligible studies in Cochrane Controlled Trials Register/CENTRAL, PubMed, EMBASE, and China Biology Medicine disc (CBMdisc) were searched until October 13, 2011. References of the included studies were hand searched. Two reviewers assessed the risk of bias and extracted the data of the included studies in duplicate. Meta-analysis was conducted with Revman 5.1. Six randomized controlled trials involving 682 participants were included. One case had low risk of bias, another one had moderate risk of bias, and the remaining four had high risk of bias. Meta-analysis showed that periodontal treatment has no significant effect on C-reactive protein, total cholesterol, low-density lipoprotein cholesterol, and triglycerides (P > 0.05). However, the treatment had a significant effect on high-density lipoprotein cholesterol [MD = 0.05, 95% CI (0.00, 0.09), P = 0.04]. Periodontal treatment has good effects on controlling high-density lipoprotein cholesterol although more randomized controlled trials must be conducted to verify its effectiveness.

Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice.

PubMed

Marquart, Tyler J; Wu, Judy; Lusis, Aldons J; Baldán, Ángel

2013-03-01

To determine the efficacy of long-term anti-miR-33 therapy on the progression of atherosclerosis in high-fat, high-cholesterol-fed Ldlr(-/-) mice. Ldlr(-/-) mice received saline, or control or anti-miR-33 oligonucleotides once a week for 14 weeks. The treatment was effective, as measured by reduced levels of hepatic miR-33 and increased hepatic expression of miR-33 targets. Analysis of plasma samples revealed an initial elevation in high-density lipoprotein cholesterol after 2 weeks of treatment that was not sustained by the end of the experiment. Additionally, we found a significant increase in circulating triglycerides in anti-miR-33-treated mice, compared with controls. Finally, examination of atheromata revealed no significant changes in the size or composition of lesions between the 3 groups. Prolonged silencing of miR-33 fails to maintain elevated plasma high-density lipoprotein cholesterol and does not prevent the progression of atherosclerosis in Ldlr(-/-) mice.

[Dyslipidemias : Diagnostics and management].

PubMed

Sinning, D; Landmesser, U

2017-09-01

For disorders of lipid metabolism the risk-adapted adjustment of low-density lipoprotein (LDL) cholesterol remains the primary treatment target, as a causal role in minimizing the progression of ACVD has been shown. Because of their efficacy in reducing cardiovascular morbidity and mortality, statins are recommended as first-line pharmacological treatment in dyslipidemias. Additionally, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have been shown to significantly reduce cardiovascular events in high-risk patients. Life style changes can improve the plasma lipid profile, particularly in the setting of hypertriglyceridemia. Evaluation of high-density lipoprotein (HDL) cholesterol and lipoprotein(a) provides further information when assessing the individual cardiovascular risk, but direct evidence that pharmacologically targeting HDL cholesterol or Lp(a) results in a reduction of cardiovascular events has not yet been shown.

Progression of Chronic Kidney Disease Affects HDL Impact on Lipoprotein Lipase (LPL)-Mediated VLDL Lipolysis Efficiency.

PubMed

Ćwiklińska, Agnieska; Cackowska, Monika; Wieczorek, Ewa; Król, Ewa; Kowalski, Robert; Kuchta, Agnieszka; Kortas-Stempak, Barbara; Gliwińska, Anna; Dąbkowski, Kamil; Zielińska, Justyna; Dębska-Ślizień, Alicja; Jankowski, Maciej

2018-06-15

Hypertriglyceridaemia (HTG) and reduction and dysfunction of high density lipoprotein (HDL) are common lipid disturbances in chronic kidney disease (CKD). HTG in CKD is caused mainly by the decreased efficiency of lipoprotein lipase (LPL)-mediated very low density lipoprotein triglyceride (VLDL-TG) lipolysis. It has not been clarified whether HDL dysfunction in CKD contributes directly to HTG development; thus, the aim of this study was to assess the impact of CKD progression on the ability of HDL to enhance LPL-mediated VLDL-TG lipolysis efficiency. VLDL was isolated from non-dialysis patients in CKD stages 3 and 4 and from non-CKD patients. The VLDL was incubated with LPL at the constant LPL:VLDL-TG ratio, in the absence or presence of HDL. After incubation, the VLDL was separated and the percentage (%) of hydrolyzed TG was calculated. HDL presence increased the lipolysis efficiency of VLDL isolated from CKD and non-CKD patients, for the VLDL-TG> 50 mg/dl. Its effect was dependent on the VLDL-TG and HDL-cholesterol concentrations in the reaction mixtures: the higher the concentrations of VLDL-TG and HDL-cholesterol, the greater the effect. The positive impact of HDL on VLDL lipolysis was modified by CKD progression: the percentage of lipolyzed VLDL-TG in the presence of HDL decreased with a reduction in eGFR (r=0.43, p=0.009), and for patients with stage 4 CKD, no positive impact of HDL on lipolysis was observed. The percentage of lipolyzed TG correlated negatively with apoE and apoCs content in VLDL, and positively with HDL-apoCII, as well as with VLDL and HDL apoCII/ apoCIII ratios. The progression of CKD was associated with unfavourable changes in VLDL and HDL composition; apoE and apoCs levels increased in VLDL with a decrease in eGFR whereas the HDL-cholesterol level decreased. The progression of CKD affects lipoprotein composition and properties, and modulates the positive impact of HDL on VLDL lipolysis efficiency. In CKD patients, HDL deficiency and dysfunction can directly affect hypertriglyceridaemia development. © 2018 The Author(s). Published by S. Karger AG, Basel.

Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets

PubMed Central

Ollila, O. H. Samuli; Lamberg, Antti; Lehtivaara, Maria; Koivuniemi, Artturi; Vattulainen, Ilpo

2012-01-01

Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface. Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence of interfacial tension becomes significant for particles with a radius of ∼5 nm, when the area per molecule in the surface region is <1.4 nm2. Further, interfacial tensions in the used HDL and LDL models are essentially unaffected by single apo-proteins at the surface. Finally, interfacial tensions of lipoproteins are higher than in thermodynamically stable droplets, suggesting that HDL and LDL are kinetically trapped into a metastable state. PMID:22995496

Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia.

PubMed

Toth, Peter P; Catapano, Alberico L; Farnier, Michel; Foody, Joanne; Tomassini, Joanne E; Jensen, Erin; Polis, Adam B; Hanson, Mary E; Musliner, Thomas A; Tershakovec, Andrew M

2016-12-15

Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of statins when given to patients who are statin naive or those on statin therapy. Copyright © 2016 The Authors and Merck Sharp & Dohme Corp. Published by Elsevier Inc. All rights reserved.

Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse

PubMed Central

Braun, Anne; Zhang, Songwen; Miettinen, Helena E.; Ebrahim, Shamsah; Holm, Teresa M.; Vasile, Eliza; Post, Mark J.; Yoerger, Danita M.; Picard, Michael H.; Krieger, Joshua L.; Andrews, Nancy C.; Simons, Michael; Krieger, Monty

2003-01-01

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5–6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between ≈3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease. PMID:12771386

Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).

PubMed

Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

2013-11-01

Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans.

Contribution of 20 single nucleotide polymorphisms of 13 genes to dyslipidemia associated with antiretroviral therapy.

PubMed

Arnedo, Mireia; Taffé, Patrick; Sahli, Roland; Furrer, Hansjakob; Hirschel, Bernard; Elzi, Luigia; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Bergmann, Sven; Beckmann, Jacques S; Telenti, Amalio; Tarr, Philip E

2007-09-01

HIV-1 infected individuals have an increased cardiovascular risk which is partially mediated by dyslipidemia. Single nucleotide polymorphisms in multiple genes involved in lipid transport and metabolism are presumed to modulate the risk of dyslipidemia in response to antiretroviral therapy. The contribution to dyslipidemia of 20 selected single nucleotide polymorphisms of 13 genes reported in the literature to be associated with plasma lipid levels (ABCA1, ADRB2, APOA5, APOC3, APOE, CETP, LIPC, LIPG, LPL, MDR1, MTP, SCARB1, and TNF) was assessed by longitudinally modeling more than 4400 plasma lipid determinations in 438 antiretroviral therapy-treated participants during a median period of 4.8 years. An exploratory genetic score was tested that takes into account the cumulative contribution of multiple gene variants to plasma lipids. Variants of ABCA1, APOA5, APOC3, APOE, and CETP contributed to plasma triglyceride levels, particularly in the setting of ritonavir-containing antiretroviral therapy. Variants of APOA5 and CETP contributed to high-density lipoprotein-cholesterol levels. Variants of CETP and LIPG contributed to non-high-density lipoprotein-cholesterol levels, a finding not reported previously. Sustained hypertriglyceridemia and low high-density lipoprotein-cholesterol during the study period was significantly associated with the genetic score. Single nucleotide polymorphisms of ABCA1, APOA5, APOC3, APOE, and CETP contribute to plasma triglyceride and high-density lipoprotein-cholesterol levels during antiretroviral therapy exposure. Genetic profiling may contribute to the identification of patients at risk for antiretroviral therapy-related dyslipidemia.

Unlike type 2 diabetes, type 1 does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene.

PubMed

Georgopoulos, Angeliki; Aras, Omer; Noutsou, Marina; Tsai, Michael Y

2002-08-01

In type 2 diabetes, the threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with elevated fasting and postprandial triglycerides and dyslipidemia when compared with the wild type (Ala-54/Ala-54). To assess whether this is the case in patients with type 1 diabetes, who usually do not manifest the metabolic syndrome, we screened 181 patients with similar glycemic control as the type 2 patients. Thirty percent were heterozygous, and 9% were homozygous for the polymorphism. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild type (n = 84), those heterozygous for Ala-54/Thr-54 (n = 44), and those homozygous for the Thr-54 (n = 13) were 1.0 +/- 0.07, 1.1 +/- 0.17, and 1.2 +/- 0.23 mmol/liter, respectively. In addition, there were no differences in total, low-density lipoprotein, high-density lipoprotein, and non-high density lipoprotein cholesterol among the three groups. After a fat load, the postprandial area under the curve of triglyceride in plasma, chylomicrons, and very low-density lipoprotein were similar between the wild type (n = 18) and the Thr-54 homozygotes (n = 12). In conclusion, in contrast to type 2, type 1 diabetes does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene to cause hypertriglyceridemia/dyslipidemia. Insulin resistance could account possibly for this difference.

Comparison of febuxostat and allopurinol for hyperuricemia in cardiac surgery patients with chronic kidney disease (NU-FLASH trial for CKD).

PubMed

Sezai, Akira; Soma, Masayoshi; Nakata, Kin-ichi; Osaka, Shunji; Ishii, Yusuke; Yaoita, Hiroko; Hata, Hiroaki; Shiono, Motomi

2015-10-01

The NU-FLASH trial demonstrated that febuxostat was more effective for hyperuricemia than allopurinol. This time, we compared these medications in patients with chronic kidney disease (CKD) from the NU-FLASH trial. In the NU-FLASH trial, 141 cardiac surgery patients with hyperuricemia were randomized to a febuxostat group or an allopurinol group. This study analyzed 109 patients with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m(2), and also analyzed 87 patients with stage 3 CKD. The primary endpoint was the serum uric acid level. Secondary endpoints included serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and high-sensitivity C-reactive protein. Among patients with an eGFR≤60 mL/min/1.73 m(2), uric acid levels were significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward. The serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, and high-sensitivity C-reactive protein were also significantly lower in the febuxostat group. Similar results were obtained in the patients with stage 3 CKD. In cardiac surgery patients with renal dysfunction, febuxostat reduced uric acid earlier than allopurinol, had a stronger renoprotective effect than allopurinol, and also had superior antioxidant and anti-inflammatory effects. Copyright © 2015. Published by Elsevier Ltd.

Role of Paraoxonase 1 Activity and Oxidative/Antioxidative Stress Markers in Patients with Acute Cerebral Infarction.

PubMed

Zhu, Hui; Zhao, Teng; Liu, Jingyao

2018-06-01

Paraoxonase1 (PON1) is an antioxidant which confers antioxidant properties to high-density lipoprotein (HDL) and prevents low-density lipoprotein (LDL) oxidation. The purpose of this study was to evaluate the activities of PON1 and oxidative/antioxidative stress markers in acute cerebral infarction. In this study, 161 patients diagnosed with acute cerebral infarction and 161 gender- and age-matched healthy controls were recruited. Based on the clinicoradiological profiles, the patients were further classified into two groups: lacunar infarction group and large-artery atherosclerosis group. We measured the individual lipid status parameters, oxidative and antioxidative stress status parameters, and PON1 activity. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and oxidative stress parameters in patients with acute cerebral infarction were significantly higher than those in the normal controls (p < 0.05). High-density lipoprotein cholesterol (HDL-C) level, PON1 activity, superoxide dismutase (SOD) activity, and antioxidative stress parameters in patients were lower than in the normal controls (p < 0.05). Superoxide anion (O2-), malondialdehyde (MDA), and PON1 levels in the lacunar infarction group were lower than in the large-artery atherosclerosis group (p < 0.05). Oxidative stress markers and PON1 activity are sensitive indicators of acute cerebral infarction. Our findings suggest a severely impaired antioxidative protection mechanism in these patients. Our study provides new insights into the pathophysiological mechanisms of acute cerebral infarction, which may also provide new therapeutic targets for ischemic cerebrovascular diseases.

Effects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans

USDA-ARS?s Scientific Manuscript database

Background: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), lowers plasma low density lipoprotein cholesterol (LDL-C) and apolipoprotein B100 (apoB). Although studies in mice and cells have identified increased hepatic LDL receptors as the basis for LDL lo...

Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials.

PubMed

Nordmann, Alain J; Nordmann, Abigail; Briel, Matthias; Keller, Ulrich; Yancy, William S; Brehm, Bonnie J; Bucher, Heiner C

2006-02-13

Low-carbohydrate diets have become increasingly popular for weight loss. However, evidence from individual trials about benefits and risks of these diets to achieve weight loss and modify cardiovascular risk factors is preliminary. We used the Cochrane Collaboration search strategy to identify trials comparing the effects of low-carbohydrate diets without restriction of energy intake vs low-fat diets in individuals with a body mass index (calculated as weight in kilograms divided by the square of height in meters) of at least 25. Included trials had to report changes in body weight in intention-to-treat analysis and to have a follow-up of at least 6 months. Two reviewers independently assessed trial eligibility and quality of randomized controlled trials. Five trials including a total of 447 individuals fulfilled our inclusion criteria. After 6 months, individuals assigned to low-carbohydrate diets had lost more weight than individuals randomized to low-fat diets (weighted mean difference, -3.3 kg; 95% confidence interval [CI], -5.3 to -1.4 kg). This difference was no longer obvious after 12 months (weighted mean difference, -1.0 kg; 95% CI, -3.5 to 1.5 kg). There were no differences in blood pressure. Triglyceride and high-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-carbohydrate diets (after 6 months, for triglycerides, weighted mean difference, -22.1 mg/dL [-0.25 mmol/L]; 95% CI, -38.1 to -5.3 mg/dL [-0.43 to -0.06 mmol/L]; and for high-density lipoprotein cholesterol, weighted mean difference, 4.6 mg/dL [0.12 mmol/L]; 95% CI, 1.5-8.1 mg/dL [0.04-0.21 mmol/L]), but total cholesterol and low-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-fat diets (weighted mean difference in low-density lipoprotein cholesterol after 6 months, 5.4 mg/dL [0.14 mmol/L]; 95% CI, 1.2-10.1 mg/dL [0.03-0.26 mmol/L]). Low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered.

Antisense oligonucleotides for the treatment of dyslipidaemia.

PubMed

Visser, Maartje E; Witztum, Joseph L; Stroes, Erik S G; Kastelein, John J P

2012-06-01

Antisense oligonucleotides (ASOs) are short synthetic analogues of natural nucleic acids designed to specifically bind to a target messenger RNA (mRNA) by Watson-Crick hybridization, inducing selective degradation of the mRNA or prohibiting translation of the selected mRNA into protein. Antisense technology has the ability to inhibit unique targets with high specificity and can be used to inhibit synthesis of a wide range of proteins that could influence lipoprotein levels and other targets. A number of different classes of antisense agents are under development. To date, mipomersen, a 2'-O-methoxyethyl phosphorothioate 20-mer ASO, is the most advanced ASO in clinical development. It is a second-generation ASO developed to inhibit the synthesis of apolipoprotein B (apoB)-100 in the liver. In Phase 3 clinical trials, mipomersen has been shown to significantly reduce plasma low-density lipoprotein cholesterol (LDL-c) as well as other atherogenic apoB containing lipoproteins such as lipoprotein (a) [Lp(a)] and small-dense LDL particles. Although concerns have been raised because of an increase in intrahepatic triglyceride content, preliminary data from long-term studies suggest that with continued treatment, liver fat levels tend to stabilize or decline. Further studies are needed to evaluate potential clinical relevance of these changes. Proprotein convertase subtilisin/kexin-9 (PCSK9) is another promising novel target for lowering LDL-c by ASOs. Both second-generation ASOs and ASOs using locked nucleic acid technology have been developed to inhibit PCSK9 and are under clinical development. Other targets currently being addressed include apoC-III and apo(a) or Lp(a). By directly inhibiting the synthesis of specific proteins, ASO technology offers a promising new approach to influence the metabolism of lipids and to control lipoprotein levels. Its application to a wide variety of potential targets can be expected if these agents prove to be clinically safe and effective.

Effect of Vitamin D, Calcium and Multiple Micronutrients Supplementation on Lipid Profile in Pre-menopausal Bangladeshi Garment Factory Workers with Hypovitaminosis D

PubMed Central

Shamim, Abu Ahmed; Ahmed, Abu; Akhtaruzzaman, Mohammad; Kärkkäinen, Merja; Lamberg-Allardt, Christel

2014-01-01

ABSTRACT Elevated total cholesterol and low-density lipoprotein cholesterol in sera are both well-known risk factors of coronary heart disease. Adequate vitamin D status is important for optimal function of many organs and tissues of our body. There is continuing controversy about the effect of adequate vitamin D consumption on serum lipids and lipoproteins. The present study assessed the effect of vitamin D, calcium and multiple micronutrients supplementation on the lipid profile in Bangladeshi young female garment factory workers who have hypovitaminosis D. This placebo-controlled intervention trial conducted over a period of one year randomly assigned a total of 200 apparently healthy subjects aged 16-36 years to 4 groups. The subjects received daily supplements of 400 IU of vitamin D (VD group) or 400 IU of vitamin D+600 mg of calcium lactate (VD-Ca group), or multiple micronutrients with 400 IU of vitamin-D+600 mg of calcium lactate (MMN-VD-Ca group), or the group consuming placebo (PL group). Serum concentrations of lipid and lipoprotein, 25-hydroxyvitamin D (25OHD) and intact parathyroid hormone (iPTH) were measured at baseline and after one year of follow-up. No significant changes in the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio were observed in the supplemented groups compared to the placebo group. Supplementation had a positive effect (p<0.05) on very low-density lipoprotein cholesterol (VLDL-C) and triacylglycerol (TAG). A negative correlation between changes in serum iPTH and HDL-C was observed, which indicated that subjects with the greatest decline in S-iPTH had the greatest increase in HDL-C. The results suggest that consumption of adequate vitamin D with calcium or MMN for one-year may have no impact on serum lipid profile in the subjects studied. Longer-term clinical trials with different doses of supplemental vitamin D are warranted in evaluating the effect of intervention. PMID:25895202

Early-stage atherosclerosis in poloxamer 407-induced hyperlipidemic mice: pathological features and changes in the lipid composition of serum lipoprotein fractions and subfractions.

PubMed

Korolenko, Tatyana A; Johnston, Thomas P; Tuzikov, Fedor V; Tuzikova, Natalia A; Pupyshev, Alexandr B; Spiridonov, Victor K; Goncharova, Natalya V; Maiborodin, Igor V; Zhukova, Natalia A

2016-01-22

The aims of this study were to evaluate the effect of poloxamer 407 administration on atherogenic serum lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids, as well as the onset of early atherosclerosis, in mice. Mice were administered either sterile saline or poloxamer 407 (to induce a dose-controlled hyperlipidemia) for 1 month and then sacrificed at 1, 4 and 10 days after the last dose of poloxamer 407. Systolic and diastolic blood pressure, the activity of a cysteine protease (cathepsin B) in cardiac and liver tissue, and histological/morphological examination of heart and liver specimens was performed for each group of mice at each time point. Lastly, small angle X-ray scattering was utilized to analyze the lipoprotein fractions and subfractions associated with cholesterol, triglycerides and phospholipids for both groups of mice at each time point. Statistical analysis was performed using one-way, analysis-of-variance with post hoc analysis to determine significantly different mean values, while correlation analysis employed the Spearman test. Poloxamer 407-treated mice revealed significant hyperlipidemia, moderately elevated blood pressure, general lipidosis in liver cells, increased cysteine protease activity in heart tissue, and contractile-type changes in cardiomyocytes. Similar to humans, the onset of atherosclerosis in poloxamer 407-treated mice was characterized by a steady increase in serum low-density, intermediate-density and very-low-density lipoprotein fractions, as well as very-low-density lipoprotein subfractions. We would propose that the sustained elevation of serum atherogenic lipoprotein fractions and subfractions induced by the administration of poloxamer 407 to mice resulted in the morphological changes we observed in both heart and liver cells, which are suggested to precede atherosclerosis, since this is a well-established mouse model of atherosclerosis. Since most of the cellular, biochemical and physiological changes documented in the present study using poloxamer 407-treated mice are related to the symptoms of early atherosclerosis in humans, it is suggested that the poloxamer 407-induced mouse model of hyperlipidemia and atherosclerosis might prove beneficial as an experimental animal model with which to evaluate the pathological features observed in early-stage atherosclerosis.

Effects of raw red onion consumption on metabolic features in overweight or obese women with polycystic ovary syndrome: a randomized controlled clinical trial.

PubMed

Ebrahimi-Mamaghani, Mehranghiz; Saghafi-Asl, Maryam; Pirouzpanah, Saeed; Asghari-Jafarabadi, Mohammad

2014-04-01

We aimed to evaluate the effects of raw red onion consumption on metabolic features in overweight and obese women with polycystic ovary syndrome. In this randomized controlled clinical trial, the patients (n=54) were randomly allocated to the intervention group as 'high-onion' (raw red onions: 2 × 40-50 g/day if overweight and 2 × 50-60 g/day if obese) or to the control group as 'low-onion' (raw red onions: 2 × 10-15 g/day) along with limited liliaceous vegetables for 8 weeks. Body mass index, dietary record, and metabolic parameters (fasting blood sugar, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lipoprotein (a)) were evaluated in the follicular phase of the menstrual cycle at baseline and after 8 weeks. Hormonal variables (progesterone, prolactin, and 17-OH progesterone) were also measured at baseline. Onion significantly decreased the levels of total cholesterol within each group; however, these changes were stronger in the high-onion group (weighted mean differences [WMD]: -5.60 [95% confidence interval [CI]: -9.16, -2.03]; P=0.003) than in the low-onion group (WMD: -6.42 [95%CI: -11.97, -0.87]; P=0.025). Similarly, low-density lipoprotein cholesterol decreased significantly (WMD: -5.13 [95%CI: -9.46, -0.81); P=0.022) in the high-onion group, and (WMD: -2.90 [95%CI -5.57, -0.21]; P=0.035) in the low-onion group after treatment. The levels of fasting blood sugar, triglycerides, high-density lipoprotein cholesterol and lipoprotein (a) did not differ significantly after 8-week onion treatment. Adjustment for confounders did not make any significant changes in any of the parameters in post-treatment levels. Raw red onion consumption appears to be effective as a cholesterol-lowering food agent in women with polycystic ovary syndrome. However, further investigation is warranted. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50.

PubMed Central

Kristenson, M.; Ziedén, B.; Kucinskienë, Z.; Elinder, L. S.; Bergdahl, B.; Elwing, B.; Abaravicius, A.; Razinkovienë, L.; Calkauskas, H.; Olsson, A. G.

1997-01-01

OBJECTIVE: To investigate possible risk factors and mechanisms behind the four times higher and diverging mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men. DESIGN: Concomitant cross sectional comparison of randomly selected 50 year old men without serious acute or chronic disease. Methods and equipment were identical or highly standardised between the centres. SETTING: Linköping (Sweden) and Vilnius (Lithuania). SUBJECTS: 101 and 109 men aged 50 in Linköping and Vilnius respectively. MAIN OUTCOME MEASURES: Anthropometric data, blood pressure, smoking, plasma lipid and lipoprotein concentrations, susceptibility of low density lipoprotein to oxidation, and plasma concentrations of fat soluble antioxidant vitamins. RESULTS: Systolic blood pressure was higher (141 v 133 mm Hg, P < 0.01), smoking habits were similar, and plasma total cholesterol (5.10 v 5.49 mmol/l, P < 0.01) and low density lipoprotein cholesterol (3.30 v 3.68 mmol/l, P < 0.01) lower in men from Vilnius compared with those from Linköping. Triglyceride, high density lipoprotein cholesterol, and Lp(a) lipoprotein concentrations did not differ between the two groups. The resistance of low density lipoprotein to oxidation was lower in the men from Vilnius; lag phase was 67.6 v 79.5 minutes (P < 0.001). Also lower in the men from Vilnius were mean plasma concentrations of lipid soluble antioxidant vitamins (beta carotene 377 v 510 nmol/l, P < 0.01; lycopene 327 v 615 nmol/l, P < 0.001; and lipid adjusted gamma tocopherol 0.25 v 0.46 mumol/mmol, P < 0.001. alpha Tocopherol concentration did not differ). Regression analysis showed that the lag phase was still significantly shorter by 10 minutes in men from Vilnius when the influence of other known factors was taken into account. CONCLUSIONS: The high mortality from coronary heart disease in Lithuania is not caused by traditional risk factors alone. Mechanisms related to antioxidant state may be important. PMID:9066473

Effect of vitamin D, calcium and multiple micronutrients supplementation on lipid profile in pre-menopausal Bangladeshi garment factory workers with hypovitaminosis D.

PubMed

Islam, Md Zahirul; Shamim, Abu Ahmed; Akhtaruzzaman, Mohammad; Kärkkäinen, Merja; Lamberg-Allardt, Christel

2014-12-01

Elevated total cholesterol and low-density lipoprotein cholesterol in sera are both well-known risk factors of coronary heart disease. Adequate vitamin D status is important for optimal function of many organs and tissues of our body. There is continuing controversy about the effect of adequate vitamin D consumption on serum lipids and lipoproteins. The present study assessed the effect of vitamin D, calcium and multiple micronutrients supplementation on the lipid profile in Bangladeshi young female garment factory workers who have hypovitaminosis D. This placebo-controlled intervention trial conducted over a period of one year randomly assigned a total of 200 apparently healthy subjects aged 16-36 years to 4 groups. The subjects received daily supplements of 400 IU of vitamin D (VD group) or 400 IU of vitamin D+600 mg of calcium lactate (VD-Ca group), or multiple micronutrients with 400 IU of vitamin-D+600 mg of calcium lactate (MMN-VD-Ca group), or the group consuming placebo (PL group). Serum concentrations of lipid and lipoprotein, 25-hydroxyvitamin D (25OHD) and intact parathyroid hormone (iPTH) were measured at baseline and after one year of follow-up. No significant changes in the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio were observed in the supplemented groups compared to the placebo group. Supplementation had a positive effect (p<0.05) on very low-density-lipoprotein cholesterol (VLDL-C) and triacylglycerol (TAG). A negative correlation between changes in serum iPTH and HDL-C was observed, which indicated that subjects with the greatest decline in S-iPTH had the greatest increase in HDL-C. The results suggest that consumption of adequate vitamin D with calcium or MMN for one-year may have no impact on serum lipid profile in the subjects studied. Longer-term clinical trials with different doses of supplemental vitamin D are warranted in evaluating the effect of intervention.

Update on the molecular biology of dyslipidemias.

PubMed

Ramasamy, I

2016-02-15

Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Monogenic hypertriglyceridemia is the result of mutations in genes that regulate the metabolism of triglyceride rich lipoproteins (eg LPL, APOC2, APOA5, LMF1, GPIHBP1). Conversely familial hypobetalipoproteinemia is caused by inactivation of the PCSK9 gene which increases the number of LDL receptors and decreases plasma cholesterol. Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can further cause low levels of apoB containing lipoproteins. Abetalipoproteinemia and chylomicron retention disease are due to mutations in the microsomal transfer protein and Sar1b-GTPase genes, which affect the secretion of apoB containing lipoproteins. Dysbetalipoproteinemia stems from dysfunctional apoE and is characterized by the accumulation of remnants of chylomicrons and very low density lipoproteins. ApoE deficiency can cause a similar phenotype or rarely mutations in apoE can be associated with lipoprotein glomerulopathy. Low HDL can result from mutations in a number of genes regulating HDL production or catabolism; apoAI, lecithin: cholesterol acyltransferase and the ATP-binding cassette transporter ABCA1. Patients with cholesteryl ester transfer protein deficiency have markedly increased HDL cholesterol. Both common and rare genetic variants contribute to susceptibility to dyslipidemias. In contrast to rare familial syndromes, in most patients, dyslipidemias have a complex genetic etiology consisting of multiple genetic variants as established by genome wide association studies. Secondary factors, obesity, metabolic syndrome, diabetes, renal disease, estrogen and antipsychotics can increase the likelihood of clinical presentation of an individual with predisposed genetic susceptibility to hyperlipoproteinemia. The genetic profiles studied are far from complete and there is room for further characterization of genes influencing lipid levels. Genetic assessment can help identify patients at risk for developing dyslipidemias and for treatment decisions based on 'risk allele' profiles. This review will present the current information on the genetics and pathophysiology of disorders that cause dyslipidemias. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of avocado-enriched diets on plasma lipoproteins: A meta-analysis.

PubMed

Peou, Sokunthea; Milliard-Hasting, Brittany; Shah, Sachin A

2016-01-01

Optimizing plasma lipoproteins is the primary goal of pharmacotherapy and diet interventions in people at risk for cardiovascular diseases. Avocados offer a rich source of monounsaturated fat and may pose beneficial effects on the lipid profile. We aimed to perform a meta-analysis of randomized clinical trials assessing the impact of avocados on TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and/or triglycerides (TG). We searched PUBMED, Cumulative Index to Nursing and Allied Health Literature, Index to Nursing and Allied Health Literature, and the Cochrane Database of Systemic Reviews from their inception to February 2015. The weighted mean difference from baseline was calculated for all endpoints. Subgroup analyses were performed to assess heterogeneity, and funnel plots inspected to assess publication bias. Ten unique studies (n = 229) were included. Avocado consumption significantly reduced TC, LDL-C, and TG by -18.80 mg/dL (95% confidence interval [CI], -24.56 to -13.05; I(2), 46.9%), -16.50 mg/dL (95% CI, -22.91 to -10.10; I(2), 72.5%), -27.20 mg/dL (95% CI, -44.41 to -9.99; I(2), 91.1%) respectively. High-density lipoprotein cholesterol decreased nonsignificantly by -0.18 mg/dL (95% CI, -3.23 to 2.88; I(2), 84.8%). Avocado-substituted diets significantly decrease TC, LDL-C, and TG levels. Substituting dietary fats with avocados versus adding to the free diet should be the primary recommendation strategy. Larger trials looking at the impact of avocados on major adverse cardiovascular events are warranted. Copyright © 2016 National Lipid Association. All rights reserved.

Serum high-density lipoprotein is associated with better cognitive function in a cross-sectional study of aging women.

PubMed

Bates, Kristyn A; Sohrabi, Hamid R; Rainey-Smith, Stephanie R; Weinborn, Michael; Bucks, Romola S; Rodrigues, Mark; Beilby, John; Howard, Matthew; Taddei, Kevin; Martins, Georgia; Paton, Athena; Shah, Tejal; Dhaliwal, Satvinder S; Foster, Jonathan K; Martins, Ian J; Lautenschlager, Nicola T; Mastaglia, Frank L; Gandy, Samuel E; Martins, Ralph N

2017-03-01

Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062; p < .05 and F = 3.2670; p < .05, respectively). Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.

Optimal Serum Cholesterol Concentrations are Associated with Accelerated Bone Loss in African Ancestry Men

PubMed Central

Kuipers, Allison L.; Miljkovic, Iva; Evans, Rhobert; Bunker, Clareann H.; Patrick, Alan L.; Zmuda, Joseph M.

2016-01-01

Purpose Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change, Methods We determined the association of serum triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up: 6.1 years) measures of BMD in a cohort of 1289 in African ancestry men (mean age: 56.4 years). Fasting serum triglycerides, HDL and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline or high-risk for triglyceride, HDL and LDL concentrations based on adult treatment panel III guidelines. Results Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p<0.05). Similarly, men classified as having optimal levels of LDL, HDL or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p<0.05), independent of potential confounding factors. Conclusions We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings. PMID:26602914

Butyrylcholinesterase (BChE) activity is associated with the risk of preeclampsia: influence on lipid and lipoprotein metabolism and oxidative stress.

PubMed

Rahimi, Zohreh; Ahmadi, Reza; Vaisi-Raygani, Asad; Rahimi, Ziba; Bahrehmand, Fariborz; Parsian, Abbas

2013-11-01

To determine the butyrylcholinesterase (BChE) activity and phenotypes in preeclampsia and its possible association with lipid and lipoprotein metabolism and oxidative stress in preeclamptic women. In a case-control study, 101 pregnant women with normal pregnancy and 198 women with preeclampsia from Western Iran were studied. The serum BChE activity and phenotypes were measured using spectrophotometric method. The apolipoprotein E (APOE) genotypes were identified using PCR-RFLP. The serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined by HPLC and commercial kits, respectively. The BChE activity and the frequency of non-usual BChE phenotype in preeclamptic women were significantly lower and higher, respectively compared to controls. There was a higher BChE activity in the presence of APOE ε3ε4 compared to ε3ε3 genotype in preeclamptic women. In addition, there were significant positive correlations between BChE activity and the levels of low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol (TC) and TAC. However, there was a negative but significant correlation between BChE activity and MDA level. Our study for the first time indicated that BChE activity might be involved in the pathogenesis of preeclampsia through influence on lipid and lipoprotein metabolism and oxidative stress.

Impact of micronized starfruit (Averrhoa carambola L.) fiber concentrate on lipid metabolism in mice.

PubMed

Herman-Lara, Erasmo; Elvira-Torales, Laura I; Rodriguez-Miranda, Jesús; Torruco-Uco, Juan G; Carmona-García, Roselis; Mendoza-García, Patricia G; García, Hugo S; Soto-Rodríguez, Ida; Sánchez-Valdivieso, Enrique; Martínez-Sánchez, Cecilia E

2014-11-01

The objective of this study was to evaluate the effect of micronized insoluble fiber from starfruit bagasse as an ingredient of a functional food (FF) or as micronized insoluble fiber-rich fraction (IFRF) and its effects in vivo on lipids metabolism in a murine model. Experimental animals were divided in four isoproteic (15.8%) treatments differing on the fiber and cholesterol level used. The micronized IFRF particle size ranged from 37.5 to 149 μm. Treatments with added IFRF and those including the FF lowered serum triacylglycerols, total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL) concentrations (IFRF: 14.2, 25.4, 55.06, and 12.18%, respectively; FF: 30.18, 39.47, 35.11, and 43.18%, respectively). IFRF produced the overall highest serum hypolipidemic effect and prevented the development of non-alcoholic fatty liver. Both the IFRF and the FF exhibited hypolipidemic effects that suggest a potential role of starfruit insoluble fiber as a component of FFs aimed against cardiovascular diseases.

Horizontal semi-dry electroblotting for the detection of the low density lipoprotein receptor in solubilized liver membranes.

PubMed

Himber, J

1993-08-01

A high efficiency transfer of the low density lipoprotein (LDL) receptor proteins from polyacrylamide slab gel onto immobilizing nitrocellulose membranes using the horizontal semi-dry electrophoretic system is described. The transfer of the LDL receptors from solubilized rat liver microsomes was performed between two graphite plate electrodes in a continuous buffer system containing methanol and sodium dodecyl sulfate. The protein transfer was achieved in only 150 min at a constant current of 0.8 mA/cm2 at room temperature with very low Joule heat development. The homogeneous electric field yield between the two electrode plates produced a satisfactory transfer of the LDL-receptor protein band in spite of its high molecular weight, and only few protein traces remained in the polyacrylamide gel after blotting. This improved method allows a rapid and quantitative transfer of the LDL receptors without protein denaturation, since the specific binding activity of the blotted receptor is retained as demonstrated by ligand-blotting and immunoblotting.

Diagnosis and treatment of high density lipoprotein deficiency.

PubMed

Schaefer, Ernst J; Anthanont, Pimjai; Diffenderfer, Margaret R; Polisecki, Eliana; Asztalos, Bela F

Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Transcriptional regulation of human Paraoxonase 1 by nuclear receptors.

PubMed

Ponce-Ruiz, N; Murillo-González, F E; Rojas-García, A E; Mackness, Mike; Bernal-Hernández, Y Y; Barrón-Vivanco, B S; González-Arias, C A; Medina-Díaz, I M

2017-04-25

Paraoxonase 1 (PON1) is a calcium-dependent lactonase synthesized primarily in the liver and secreted into the plasma, where it is associates with high density lipoproteins (HDL). PON1 acts as antioxidant preventing low-density lipoprotein (LDL) oxidation, a process considered critical in the initiation and progression of atherosclerosis. Additionally, PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs). Thus, PON1 activity and expression levels are important for determining susceptibility to OPs intoxication and risk of developing diseases related to inflammation and oxidative stress. Increasing evidence has demonstrated the modulation of PON1 expression by many factors is due to interaction with nuclear receptors (NRs). Here, we briefly review the studies in this area and discuss the role of nuclear receptors in the regulation of PON1 expression, as well as how understanding these mechanisms may allow us to manipulate PON1 levels to improve drug efficacy and treat disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Separation and characterization of high-density lipoprotein subpopulations by gel permeation chromatography.

PubMed

Clifton, P M; MacKinnon, A M; Barter, P J

1987-02-20

High-density lipoproteins (HDL) contain at least five distinct subpopulations when analyzed by gradient gel electrophoresis. This report represents the first description of a simple technique for isolating these subpopulations of HDL in quantities sufficient to enable characterization in terms of particle size, apolipoprotein AI and apolipoprotein AII content and chemical composition. Lipoproteins were separated and subfractionated on a column of Superose 6B using a fast protein liquid chromatography system. Five normal subjects were studied: HDL2b and HDL3a were isolated as essentially single subpopulations from all subjects, while HDL2a could be isolated from only three of the subjects. HDL3b was isolated in a relatively impure form (70%) from all subjects. Identical subpopulations were identified in each subject by gradient gel electrophoresis of unseparated HDL.

Impact of iron overload on interleukin-10 levels, biochemical parameters and oxidative stress in patients with sickle cell anemia

PubMed Central

Barbosa, Maritza Cavalcante; dos Santos, Talyta Ellen Jesus; de Souza, Geane Félix; de Assis, Lívia Coêlho; Freitas, Max Victor Carioca; Gonçalves, Romélia Pinheiro

2013-01-01

Objective The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. Methods A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. Results Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. Conclusion The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia. PMID:23580881

In Vitro Antioxidant and In Vivo Hypolipidemic Effects of the King Oyster Culinary-Medicinal Mushroom, Pleurotus eryngii var. ferulae DDL01 (Agaricomycetes), in Rats with High-Fat Diet-Induced Fatty Liver and Hyperlipidemia.

PubMed

Choi, Jun-Hui; Kim, Dae-Won; Kim, Seung; Kim, Sung-Jun

2017-01-01

We investigated the effect of the culinary-medicinal mushroom Pleurotus eryngii var. ferulae DDL01 on oxidative damage in the liver and brain and a high-fat/high-cholesterol-induced hyperlipidemic model. In in vitro studies, the water extracts of the fruiting bodies showed strong scavenging activities of DPPH (139.46 ± 3.2 μg) and hydroxyl (139.46 ± 3.2 μg) radicals. Moreover, the extracts showed Fe2+ chelating and reducing abilities, as well as a large amount of polyphenols and an inhibitory effect on lipid peroxidation in the liver and brain tissues. The rats were fed a pellet diet (7.5 g/rat/day) containing P. eryngii var. ferulae DDL01 (PD) for 3 weeks. In the high-fat/high-cholesterol-induced hyperlipidemic rat model, administration of PD caused a significant decrease (P < 0.05) in the levels of serum triacylglycerols, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, aspartate aminotransferase, and alanine aminotransferase and a significant increase (P < 0.05) in the level of high-density lipoprotein cholesterol. PD administration significantly decreased high-fat/high-cholesterol-induced hepatic lipid accumulation. Treatment with the extracts (up to 500 μg/mL) did not significantly affect the viability of HepG2 and 3T3-L1 cells. Our findings suggest that this mushroom has potential as an antiatherogenic dietary source in the development of therapeutic agents and functional foods.

Lecithin has no effect on serum lipoprotein, plasma fibrinogen and macro molecular protein complex levels in hyperlipidaemic men in a double-blind controlled study.

PubMed

Oosthuizen, W; Vorster, H H; Vermaak, W J; Smuts, C M; Jerling, J C; Veldman, F J; Burger, H M

1998-06-01

To examine the effects of lecithin on serum lipoprotein, plasma fibrinogen and macro molecular protein complex (MPC) levels. Twenty free living hyperlipidaemic men participated in this double-blind study which controlled for possible indirect effects. The subjects were randomly assigned to one of three treatments: frozen yoghurt or frozen yoghurt with 20 g soya bean lecithin or frozen yoghurt with 17 g sunflower oil. Sunflower oil was used to control for the increased energy and linoleic acid intake from lecithin. Yoghurt served as the 'vehicle' for the lecithin and sunflower oil and yoghurt alone was given to one group to control for possible effects due to the yoghurt 'vehicle', as well as other environmental influences. Variables were measured with standard methods twice at baseline and after 2 and 4 weeks of treatment. Plasma linoleic acid levels increased significantly with lecithin and sunflower oil treatments indicating that compliance to the treatments were obtained. Lecithin treatment did not have significant effects on serum total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A, apolipoprotein B or lipoprotein (a) levels. Plasma fibrinogen and MPC levels were also not affected by lecithin therapy. Sunflower oil treatment resulted in significant increased body weight, serum TC and decreased MPC levels. Lecithin treatment had no independent effects on serum lipoprotein, plasma fibrinogen or MPC levels in hyperlipidaemic men.

The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine.

PubMed

Stucchi, A F; Terpstra, A H; Foxall, T L; Nicolosi, R J; Smith, S C

1991-05-01

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.

In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL.

PubMed

Gan, Chaoye; Wang, Zhexuan; Chen, Yong

2017-04-01

The major apolipoproteins of plasma lipoproteins play vital roles in the structural integrity and physiological functions of lipoproteins. More than ten structural models of apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoprotein (HDL), have been developed successively. In these models, apoA-I was supposed to organize in a ring-shaped form. To date, however, there is no direct evidence under physiological condition. Here, atomic force microscopy (AFM) was used to in situ visualize the organization of apoA-I, which was exposed via depletion of the lipid component of plasma HDL pre-immobilized on functionalized mica sheets. For the first time, the ring-shaped coarse structure and three detailed structures (crescent-shaped, gapped "O"-shaped, and parentheses-shaped structures, respectively) of apoA-I in plasma HDL, which have the ability of binding scavenger receptors, were directly observed and quantitatively measured by AFM. The three detailed structures probably represent the different extents to which the lipid component of HDL was depleted. Data on lipid depletion of HDL may provide clues to understand lipid insertion of HDL. These data provide important information for the understanding of the structure/maturation of plasma HDL. Moreover, they suggest a powerful method for directly visualizing the major apolipoproteins of plasma lipoproteins or the protein component of lipoprotein-like lipid-protein complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolfe, Adam R.; Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas; Atkinson, Rachel L.

Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL),more » or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients and IBC patient-derived cell lines. A more expansive study is needed to verify these observations.« less

Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides.

PubMed

Graham, Mark J; Lee, Richard G; Brandt, Teresa A; Tai, Li-Jung; Fu, Wuxia; Peralta, Raechel; Yu, Rosie; Hurh, Eunju; Paz, Erika; McEvoy, Bradley W; Baker, Brenda F; Pham, Nguyen C; Digenio, Andres; Hughes, Steven G; Geary, Richard S; Witztum, Joseph L; Crooke, Rosanne M; Tsimikas, Sotirios

2017-07-20

Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins. We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1.0 to 1.7 mmol per liter] or >150 mg per deciliter, depending on the dose group) were randomly assigned to receive subcutaneous injections of placebo or an antisense oligonucleotide targeting ANGPTL3 mRNA in a single dose (20, 40, or 80 mg) or multiple doses (10, 20, 40, or 60 mg per week for 6 weeks). The main end points were safety, side-effect profile, pharmacokinetic and pharmacodynamic measures, and changes in levels of lipids and lipoproteins. The treated mice had dose-dependent reductions in levels of hepatic Angptl3 mRNA, Angptl3 protein, triglycerides, and low-density lipoprotein (LDL) cholesterol, as well as reductions in liver triglyceride content and atherosclerosis progression and increases in insulin sensitivity. After 6 weeks of treatment, persons in the multiple-dose groups had reductions in levels of ANGPTL3 protein (reductions of 46.6 to 84.5% from baseline, P<0.01 for all doses vs. placebo) and in levels of triglycerides (reductions of 33.2 to 63.1%), LDL cholesterol (1.3 to 32.9%), very-low-density lipoprotein cholesterol (27.9 to 60.0%), non-high-density lipoprotein cholesterol (10.0 to 36.6%), apolipoprotein B (3.4 to 25.7%), and apolipoprotein C-III (18.9 to 58.8%). Three participants who received the antisense oligonucleotide and three who received placebo reported dizziness or headache. There were no serious adverse events. Oligonucleotides targeting mouse Angptl3 retarded the progression of atherosclerosis and reduced levels of atherogenic lipoproteins in mice. Use of the same strategy to target human ANGPTL3 reduced levels of atherogenic lipoproteins in humans. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov number, NCT02709850 .).

[Association between venous thrombosis and dyslipidemia].

PubMed

García Raso, Aránzazu; Ene, Gabriela; Miranda, Carolina; Vidal, Rosa; Mata, Raquel; Llamas Sillero, M Pilar

2014-07-07

Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P<.0001). Of a total of 313 patients included in the study, 31% (n=97) had a recurrent thrombotic event and 23% (n=72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P=.008) and OR 2.35 (95% CI 1.24-4.45; P=.008), respectively, and post-thrombotic syndrome, OR 3.44 (95% CI 1.43-8.83; P=.005) and OR 2.35 (95% CI 1.24-4.45; P=.008). Our study confirmed the association between dyslipidemia and VTE and showed a risk of thrombosis nearly 4 times higher in individuals with this disease. In addition, alterations in the lipid profile were also related to a higher prevalence of thrombotic complications, recurrence and post-thrombotic syndrome. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Vitamin D Improves Selected Metabolic Parameters but Not Neuropsychological or Quality of Life Indices in OSA: A Pilot Study.

PubMed

Kerley, Conor P; Hutchinson, Katrina; Bramham, Jessica; McGowan, Aisling; Faul, John; Cormican, Liam

2017-01-15

Our group and others have reported a high rate of vitamin D deficiency in obstructive sleep apnea (OSA), where vitamin D levels (25(OH) D) correlate negatively with OSA severity and some of its associated metabolic alterations. Data regarding vitamin D supplementation in OSA are lacking. We wanted to evaluate the effect of vitamin D 3 supplementation on OSA symptoms and metabolic parameters. We conducted a pilot, double-blind, randomized, placebo-controlled trial of daily supplementation with 4,000 IU vitamin D 3 (D3) or placebo (PL). We studied 19 Caucasian adults (14 male, mean age 55 y, mean body mass index [BMI] 30.4 kg/m 2 ) with OSA. Fifteen patients were stable on continuous positive airways pressure (CPAP) therapy, whereas four were CPAP naïve. Assessments were completed at baseline and after 15 weeks of supplementation. Outcomes included sleepiness (Epworth Sleepiness Scale), quality of life (Sleep Apnea Quality of Life Inventory), fatigue (fatigue severity scale) and neuropsychological function (trail making test and Connor's Continuous Performance Test II). In addition, we assessed biochemical indices of vitamin D status (25(OH)D, calcium), inflammation (high sensitivity C-reactive protein, and lipoprotein-associated phospholipase A2), lipids (total cholesterol [low-density and high-density lipoprotein]) and glycemic indices (fasting glucose, oral glucose tolerance test). There was no change in BMI, medication, or CPAP usage. Although there was no change in neuropsychological or quality of life indices, we observed a significant increase in 25(OH)D (p = 0.00001) and significant decreases in both low-density lipoprotein (p = 0.04) and lipoprotein-associated phospholipase A2 (p = 0.037) as well as trends toward decreased fasting glucose (p = 0.09) and increased high-density lipoprotein (p = 0.07) in the D 3 group compared to PL. Vitamin D 3 supplementation increased vitamin D levels and decreased metabolic markers compared to placebo. Larger trials are required. © 2017 American Academy of Sleep Medicine

Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease

PubMed Central

2010-01-01

Background The search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis. Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis. PMID:20799970

The effect of an apolipoprotein A-I-containing high-density lipoprotein-mimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study.

PubMed

Hovingh, G Kees; Smits, Loek P; Stefanutti, Claudia; Soran, Handrean; Kwok, See; de Graaf, Jacqueline; Gaudet, Daniel; Keyserling, Constance H; Klepp, Heather; Frick, Jennifer; Paolini, John F; Dasseux, Jean-Louis; Kastelein, John J P; Stroes, Erik S

2015-05-01

Patients with homozygous familial hypercholesterolemia (HoFH) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth. Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention, but the residual risk in HoFH remains high, emphasizing the need for additional therapies. In the present study, we evaluated the effect of serial infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle, on carotid artery wall dimensions in patients with HoFH. Twenty-three patients (mean age 39.4 ± 13.5 years, mean LDL-C 214.2 ± 81.5 mg/dL) with genetically confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before and 1 hour after the first infusion, lipid values were measured. Magnetic resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions. After CER-001 infusion, apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point) decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up, P = .0835). In HoFH, 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle resulted in a significant reduction in carotid mean vessel wall area, implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy. This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH. Copyright © 2015 Mosby, Inc. All rights reserved.

Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits.

PubMed

Narita, Hiroshi; Chen, Sen; Komori, Kimihiro; Kadomatsu, Kenji

2008-06-01

Neointimal hyperplasia is strikingly suppressed in an endothelium injury model in mice deficient in the growth factor midkine. Knockdown of midkine expression by means of antisense oligonucleotide or small interfering RNA has been shown to lead to suppression of neointimal hyperplasia in a balloon injury model and a rabbit vein graft model; therefore, midkine is an essential factor for neointimal hyperplasia. These findings, however, do not necessarily apply to the function of midkine in vascular stenoses such as in-stent restenosis, because human vascular stenosis is often accompanied by atherosclerosis. We investigated midkine expression in the neointima induced by implantation of a bare metal stent in the atheromatous lesions of hypercholesterolemic rabbits. We analyzed midkine expression during a THP-1 cell differentiation and in peritoneal macrophages exposed to low-density lipoprotein or oxidized low-density lipoprotein. Midkine expression reached the maximum level within 7 days after stenting and was detected in infiltrating macrophages. Differentiation of THP-1 cells to macrophage-like cells did not trigger midkine expression. Neither low-density lipoprotein nor oxidized low-density lipoprotein enhanced midkine expression in peritoneal macrophages that had been activated by thioglycollate, although these cells expressed a significant amount of midkine. The results indicate that macrophages are the major source of midkine in the atherosclerotic neointima. The amount of midkine expressed in macrophages may be sufficient (ie, further enhancement of the expression is not necessary) for the pathogenesis, because oxidized low-density lipoprotein stimulation did not induce the midkine expression. The growth factor midkine is induced during vascular stenosis in mouse and rat models with normal diet. Knockdown of midkine expression suppresses neointimal hyperplasia. The vascular response after stenting differs from that after balloon injury in that the inflammation is more prolonged and the accumulation of macrophages is more abundant in stent-injured vessel. We found here that macrophages are the major source of midkine in the atherosclerotic neointima of in-stent restenosis in hypercholesterolemic rabbits. Our data suggest that midkine has an important role in in-stent restenosis of atherosclerotic vessels and is a candidate molecular target to prevent in-stent restenosis.

The effect of omega-3 carboxylic acids on apolipoprotein CIII-containing lipoproteins in severe hypertriglyceridemia.

PubMed

Morton, Allyson M; Furtado, Jeremy D; Lee, Jane; Amerine, William; Davidson, Michael H; Sacks, Frank M

Lipoprotein subspecies containing apoCIII adversely affect cardiovascular disease (CVD) risk; for example, low density lipoprotein (LDL) with apoCIII is a stronger CVD predictor than LDL without apoCIII. The Epanova for Lowering Very High Triglycerides (EVOLVE) trial showed that Epanova (omega-3 carboxylic acids [OM3-CA]) significantly lowered TG and apoCIII but raised LDL-C. However, it is unknown what subspecies of LDL were affected by treatment. To determine how lipoprotein subspecies are affected by omega-3 fatty acid treatment, we studied the effect of OM3-CA on apoCIII concentrations in high density lipoprotein (HDL), LDL, and very low density lipoprotein (VLDL) and on the concentrations of subspecies of HDL, LDL, and VLDL that contain or do not contain apoCIII. We analyzed plasma from a subset of subjects from the EVOLVE trial, a 12-week double-blind study of 399 subjects with fasting TG of 500 to 2000 mg/dL who were randomized to OM3-CA 2, 3, or 4 g/d or olive oil (placebo). OM3-CA significantly reduced plasma apoCIII relative to placebo, as well as apoCIII in HDL, and apoCIII in LDL. Treatment did not significantly affect the concentration of LDL with apoCIII, a subspecies highly associated with CVD risk. OM3-CA increased selectively the concentration of LDL that does not contain apoCIII, a subspecies with a weak relation to coronary heart disease. The reduction in apoCIII was associated with plasma increases in eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid and decreases in linoleic, palmitic, and oleic acids. Reduction in apoCIII may be a mechanism for the TG-lowering effects of OM3-CA. The increase in LDL-C seen in the EVOLVE trial may not be associated with increased risk of CVD. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

PubMed Central

Toth, Peter P

2016-01-01

Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant’s effect on TG levels correlating with the magnitude of the variant’s effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the available epidemiological, clinical, and genetic evidence relating to the atherogenicity of TRLs and their role in the progression of CVD. PMID:27226718

Influence of liver cancer on lipid and lipoprotein metabolism

PubMed Central

Jiang, Jingting; Nilsson-Ehle, Peter; Xu, Ning

2006-01-01

Liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma (HCC) is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. This has been attributed to the high incidence of hepatitis B infection. Hepatitis B proteins, such as the hepatitis B X protein (HBx) that is large hepatitis B surface protein could regulate transcription of many candidate genes for liver carcinogenesis. It has known that patients who suffered from acute hepatitis B could have lipid disorders such as decreased plasma level of high-density lipoproteins (HDL). Furthermore, aberrations of lipid metabolism are often seen in the chronic hepatitis B infection. Plasma lipid profiles could be changed under HCC. In majority of the reports in HCC, plasma levels of triglycerides (TG), cholesterol, free fatty acids (FFA), HDL, low-density lipoproteins (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (apoAI) and apoB were slight to significantly decreased, however, in some cases plasma levels of TG and Lp(a) might be increased. It has been suggested that analysis of plasma levels of lipids, lipoproteins and apolipoproteins in the patients suffered from HCC reflects on the hepatic cellular impairment status. Studies revealed that alterations seen in the plasma levels of lipids, lipoproteins and apolipoproteins reflecting patients' pathologic conditions. Decreased serum levels of cholesterol and apoAI may indicate a poor prognosis. Human leukaemic cells and certain tumor tissues have a higher receptor-mediated uptake of HDL and LDL than the corresponding normal cells or tissues. LDL and HDL have therefore been proposed as a carrier for the water-insoluble anti-cancer agents. PMID:16515689

Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women.

PubMed

Shidfar, Farzad; Ehramphosh, Elham; Heydari, Iraj; Haghighi, Ladan; Hosseini, Sharieh; Shidfar, Shahrzad

2009-05-01

Because of an unfavorable serum lipoprotein profile, postmenopausal women are at risk of cardiovascular disease. Soy protein may help protect against these risk factors, although its effect on paraoxonase 1 (PON1) is not clear. The aim of the present study was to determine the effects of soy protein on serum concentration of lipoproteins and PON1 activity in hypercholesterolemic postmenopausal women. In a double-blind randomized clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal women were randomly assigned to 50 g/day soy protein containing 164 mg isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were measured at baseline and at the 10th week. There was significant increase in PON1 activity (P=0.029) and a significant decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and P=0.029, respectively) at the end of the study. Similarly, PON1 activity was significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL-C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016 and P=0.001) at the end of the study compared with the beginning value in soy group. Soy protein reduces the cardiovascular disease risk in postmenopausal women because of both modest reductions in serum lipoproteins and an increase in PON1 activity.

One precursor, three apolipoproteins: the relationship between two crustacean lipoproteins, the large discoidal lipoprotein and the high density lipoprotein/β-glucan binding protein.

PubMed

Stieb, Stefanie; Roth, Ziv; Dal Magro, Christina; Fischer, Sabine; Butz, Eric; Sagi, Amir; Khalaila, Isam; Lieb, Bernhard; Schenk, Sven; Hoeger, Ulrich

2014-12-01

The novel discoidal lipoprotein (dLp) recently detected in the crayfish, differs from other crustacean lipoproteins in its large size, apoprotein composition and high lipid binding capacity, We identified the dLp sequence by transcriptome analyses of the hepatopancreas and mass spectrometry. Further de novo assembly of the NGS data followed by BLAST searches using the sequence of the high density lipoprotein/1-glucan binding protein (HDL-BGBP) of Astacus leptodactylus as query revealed a putative precursor molecule with an open reading frame of 14.7 kb and a deduced primary structure of 4889 amino acids. The presence of an N-terminal lipid bind- ing domain and a DUF 1943 domain suggests the relationship with the large lipid transfer proteins. Two-putative dibasic furin cleavage sites were identified bordering the sequence of the HDL-BGBP. When subjected to mass spectroscopic analyses, tryptic peptides of the large apoprotein of dLp matched the N-terminal part of the precursor, while the peptides obtained for its small apoprotein matched the C-terminal part. Repeating the analysis in the prawn Macrobrachium rosenbergii revealed a similar protein with identical domain architecture suggesting that our findings do not represent an isolated instance. Our results indicate that the above three apolipoproteins (i.e HDL-BGBP and both the large and the small subunit of dLp) are translated as a large precursor. Cleavage at the furin type sites releases two subunits forming a heterodimeric dLP particle, while the remaining part forms an HDL-BGBP whose relationship with other lipoproteins as well as specific functions are yet to be elucidated.

Low Impact of Traditional Risk Factors on Carotid Intima-Media Thickness: The ELSA-Brasil Cohort.

PubMed

Santos, Itamar S; Alencar, Airlane P; Rundek, Tatjana; Goulart, Alessandra C; Barreto, Sandhi M; Pereira, Alexandre C; Benseñor, Isabela M; Lotufo, Paulo A

2015-09-01

There is little information about how much traditional cardiovascular risk factors explain common carotid artery intima-media thickness (CCA-IMT) variance. We aimed to study to which extent CCA-IMT values are determined by traditional risk factors and which commonly used measurements of blood pressure, glucose metabolism, lipid profile, and adiposity contribute the most to this determination in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort baseline. We analyzed 9792 individuals with complete data and CCA-IMT measurements. We built multiple linear regression models using mean left and right CCA-IMT as the dependent variable. All models were stratified by sex. We also analyzed individuals stratified by 10-year coronary heart disease risk and, in separate, those with no traditional risk factors. Main models' R(2) varied between 0.141 and 0.373. The major part of the explained variance in CCA-IMT was because of age and race. Indicators of blood pressure, lipid profile, and adiposity that most frequently composed the best models were pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference. The association between neck circumference and CCA-IMT persisted significant even after further adjustment for vessel sizes and body mass index. Indicators of glucose metabolism had smaller contribution. We found that >60% of CCA-IMT were not explained by demographic and traditional cardiovascular risk factors, which highlights the need to study novel risk factors. Pulse pressure, low-density lipoprotein/high-density lipoprotein ratio, and neck circumference were the most consistent contributors. © 2015 American Heart Association, Inc.

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study.

PubMed

Chen, Yimin; Zhao, Ying; Feng, Linmin; Zhang, Jie; Zhang, Juanwen; Feng, Guofang

2016-04-27

Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population. A cross-sectional study was performed with 7,755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome. Participants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides. These results suggest a significant association between alpha-fetoprotein and metabolic syndrome.

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Liu, Liping; Gao, Xiang; Zhou, Yong; Wang, Chunxue; Zhang, Qian; Wang, Anxin; Hussain, Mohammed; Sun, Baoying; Wu, Shouling; Zhao, Xingquan

2013-06-01

To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population. We performed a four-year cohort study of 95 778 men and women, aged 18-98 years, selected from the Kailuan study (2006-2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared. During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01-1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24-1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference). Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

PubMed Central

St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH

2002-01-01

Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent. PMID:11825344

Effects of Apple Consumption on Lipid Profile of Hyperlipidemic and Overweight Men

PubMed Central

Vafa, Mohammad Reza; Haghighatjoo, Elham; Shidfar, Farzad; Afshari, Shirin; Gohari, Mahmood Reza; Ziaee, Amir

2011-01-01

Objectives: Fruits and vegetables may be beneficial on lipid profile of hyperlipidemic subjects. The present study was aimed to verify the effect of golden delicious apple on Lipid Profile in hyperlipidemic and overweight men. Methods: Forty six hyperlipidemic and overweight men were randomly divided into two groups. Intervention group received 300g golden delicious apple per day for 8 weeks. Control group had the regular dietary regimen for the same period of time. Blood samples were analyzed for serum triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), very low density lipoprotein-cholesterol (VLDL), apolipoprotein B (Apo B), lipoprotein a (Lp a) and LDL/HDL ratio at baseline and after intervention. Results: Total polyphenols and fibers were 485 mg/kg and 4.03 g/100g in fresh apple respectively. After 8 weeks, significant statistical differences were observed considering the TG and VLDL levels between two groups, but no significant differences were observed regarding TC, LDL-C, HDL-C, Apo (B), Lp (a) and LDL/HDL ratio. Conclusions: Consumption of Golden delicious apple may be increased serum TG and VLDL in hyperlipidemic and overweight men. We need more studies to assay the effect of apple consumption on serum TC, LDL-C, HDL-C, Apo (B), Lp (a) and LDL/HDL ratio. PMID:21603015

Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.

PubMed

Brianza-Padilla, Malinalli; Bonilla-Jaime, Herlinda; Almanza-Pérez, Julio César; López-López, Ana Laura; Sánchez-Muñoz, Fausto; Vázquez-Palacios, Gonzalo

2016-03-01

Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.

Low density lipoproteins develop resistance to oxidative modification due to inhibition of cholesteryl ester transfer protein by a monoclonal antibody.

PubMed

Sugano, M; Sawada, S; Tsuchida, K; Makino, N; Kamada, M

2000-01-01

Although numerous studies have investigated the relationship between cholesteryl ester transfer protein (CETP) and high density lipoprotein (HDL) remodeling, the relationship between CETP and low density lipoproteins (LDL) is still not fully understood. In the present study, we examined the effect of the inhibition of CETP on both LDL oxidation and the uptake of the oxidized LDL, which were made from LDL under condition of CETP inhibition, by macrophages using a monoclonal antibody (mAb) to CETP in incubated plasma. The 6-h incubation of plasma derived from healthy, fasting human subjects led to the transfer of cholesteryl ester (CE) from HDL to VLDL and LDL, and of triglycerides (TG) from VLDL to HDL and LDL. These net mass transfers of neutral lipids among the lipoproteins were eliminated by the mAb. The incubation of plasma either with or without the mAb did not affect the phospholipid compositions in any lipoproteins. As a result, the LDL fractionated from the plasma incubated with the mAb contained significantly less CE and TG in comparison to the LDL fractionated from the plasma incubated without the mAb. The percentage of fatty acid composition of LDL did not differ among the unincubated plasma, the plasma incubated with the mAb, and that incubated without the mAb. When LDL were oxidized with CuSO4, the LDL fractionated from the plasma incubated with the mAb were significantly resistant to the oxidative modification determined by measuring the amount of TBARS and by continuously monitoring the formation of the conjugated dienes, in comparison to the LDL fractionated from the plasma incubated without the mAb. The accumulation of cholesteryl ester of oxidized LDL, which had been oxidized for 2 h with CuSO4, in J774.1 cells also decreased significantly in the LDL fractionated from the plasma incubated with mAb in comparison to the LDL fractionated from the plasma incubated without the mAb. These results indicate that CETP inhibition reduces the composition of CE and TG in LDL and makes the LDL resistant to oxidation. In addition, the uptake of the oxidized LDL, which was made from the LDL under condition of CETP inhibition, by macrophages also decreased.

PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia

PubMed Central

Santos, Raul D.

2016-01-01

Abstract Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid‐modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low‐density lipoprotein cholesterol, as well as reductions in non‐high‐density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long‐term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid‐modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia. PMID:27195910

Management of Dyslipidemia in Women in the Post–hormone Therapy Era

PubMed Central

Mosca, Lori

2005-01-01

OBJECTIVE Cardiovascular disease (CVD) is the leading cause of death for women in the United States and is largely preventable. The American Heart Association has recently released evidence-based guidelines for the prevention of CVD in women; these include gender-specific recommendations for the management of dyslipidemia. This article reviews these recommendations and the evidence supporting them. DESIGN This was a qualitative review of a systematic literature search related to lipid guidelines for women and discussion of rationale and evidence for new clinical recommendations. MAIN RESULTS Lifestyle modifications are the cornerstone of lipid management. Substantial evidence from randomized clinical trials supports the use of low-density lipoprotein cholesterol–lowering therapy (primarily statins) in all high-risk women and the use of niacin or fibrates when high-density lipoprotein cholesterol is low or non-high-density lipoprotein cholesterol is elevated. Fewer data are available for women at lower or intermediate risk. CONCLUSIONS Encouragement of lifestyle modification and appropriate use of lipid-altering therapy will have a substantial impact on reducing the burden of cardiovascular disease in women. PMID:15836536

Oxidized low-density lipoprotein and upregulated expression of osteonectin and bone sialoprotein in vascular smooth muscle cells.

PubMed

Farrokhi, Effat; Samani, Keihan Ghatreh; Chaleshtori, Morteza Hashemzadeh

2014-01-01

Oxidative stress has been associated with the progression of atherosclerosis and activation of genes that lead to increased deposition of proteins in the extracellular matrix. Bone sialoprotein (BSP) and osteonectin are proteins involved in the initiation and progression of vascular calcification. To investigate the effect of oxidized low-density lipoprotein on osteonectin and BSP expression in human aorta vascular smooth muscle cells (HA/VSMCs). We treated HA/VSMCs with oxidized low-density lipoprotein (oxLDL) and measured the relative expression of osteonectin and BSP genes using the real-time polymerase chain reaction (PCR) method. We investigated the protein levels produced by each gene using the western blotting technique. oxLDL increased osteonectin and BSP levels (mean [SD], 9.1 [2.1]-fold and 4.2 [0.75]-fold, respectively) after 48 hours. The western blotting results also confirmed the increased levels of osteonectin and BSP. oxLDL may enhance vascular calcification by promoting the expression of osteonectin and BSP. Copyright© by the American Society for Clinical Pathology (ASCP).

The Short-Term Effect of Ketogenic Diet on Carotid Intima-Media Thickness and Elastic Properties of the Carotid Artery and the Aorta in Epileptic Children.

PubMed

Doksöz, Önder; Güzel, Orkide; Yılmaz, Ünsal; İşgüder, Rana; Çeleğen, Kübra; Meşe, Timur; Uysal, Utku

2015-10-01

The aim of this prospective study is to investigate the effect of a 6-month-long ketogenic diet on carotid intima-media thickness, carotid artery, and aortic vascular functions. Thirty-eight drug-resistant epileptic patients who were being treated with ketogenic diet were enrolled. Fasting total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and glucose concentrations were measured and echocardiography was performed in all patients before the beginning of ketogenic diet and at the sixth month of treatment. The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P < .05). Carotid intima-media thickness, elastic properties of the aorta, and carotid artery did not change at the sixth month of therapy compared to baseline values. A 6-month-long ketogenic diet has no effect on carotid intima-media thickness and elastic properties of the carotid artery and the aorta. © The Author(s) 2015.

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies.

PubMed

van der Lee, Sven J; Teunissen, Charlotte E; Pool, René; Shipley, Martin J; Teumer, Alexander; Chouraki, Vincent; Melo van Lent, Debora; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Haller, Toomas; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francisca A; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; Willems van Dijk, Ko; Weinhold, Leonie; Ikram, M Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P Eline; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharina E M; Vasan, Ramachandran S; Maier, Wolfgang; Peeters, Carel F W; Jörgen Grabe, Hans; Ramirez, Alfredo; Seshadri, Sudha; Metspalu, Andres; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayşe; Boomsma, Dorret I; van der Flier, Wiesje M; Amin, Najaf; van Duijn, Cornelia M

2018-06-01

Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Modulation of beta-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family.

PubMed

Cam, Judy A; Bu, Guojun

2006-08-18

Amyloid-beta peptide (Abeta) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Abeta is produced by proteolytic processing of a transmembrane protein, beta-amyloid precursor protein (APP), by beta- and gamma-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to Abeta. Recent studies have shown that members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apolipoprotein E (apoE) receptor 2, interact with APP and regulate its endocytic trafficking. Another common feature of these receptors is their ability to bind apoE, which exists in three isoforms in humans and the presence of the epsilon4 allele represents a genetic risk factor for AD. In this review, we summarize the current understanding of the function of these apoE receptors with a focus on their role in APP trafficking and processing. Knowledge of the interactions between these distinct low-density lipoprotein receptor family members and APP may ultimately influence future therapies for AD.

Vascular compliance in women with polycystic ovary syndrome and healthy women.

PubMed

Muneyyirci-Delale, Ozgul; Winer, Nathaniel; Oklander, Vita; Joulak, Ibrahim; Dalloul, Nezar; Nacharaju, Vijaya; Dham, Shefali; von Gizycki, Hans

2007-01-01

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in women of reproductive age, has been associated with the cardiometabolic syndrome and increased risk for cardiovascular diseases. Large (C1) and small (C2) vessel compliance and fasting lipids were measured in 45 healthy women and 36 women with PCOS. There were no differences in vacular compliance (C1, C2) between the 2 groups. Systolic blood pressure (116.8 vs 124.3 mm Hg; P=.01), mean arterial pressure (82.5 vs 87 mm Hg; P=.03), and low-density lipoprotein cholesterol (98.1 vs 119 mg/dL; P=.001) were significantly higher in the PCOS group. This difference was not significant after adjusting for age and body mass index. High-density lipoprotein levels in subjects with PCOS were significantly lower than in healthy women (60.2 vs 48.9 mg/dL, P=.02) even after adjusting for age and body mass index. The study indicates that obesity and low high-density lipoprotein are the major contributing factors to cardiovascular changes in PCOS.

High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis.

PubMed

Sugano, M; Tsuchida, K; Makino, N

2000-06-16

High-density lipoproteins (HDL) levels have been shown to be inversely correlated with coronary heart disease, but the mechanisms of the direct protective effect of HDL on endothelial cells are not fully understood. The apoptosis of endothelial cells induced by cytokines and/or oxidized low-density lipoproteins, etc. may provide a mechanistic clue to the "response-to-injury" hypothesis of atherogenesis. Here we report that HDL prevent the apoptosis of human umbilical venous endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha) via an inhibition of CPP32-like protease activity. The incubation of HUVECs with TNF-alpha significantly increased the CPP32-like protease activity, and induced apoptosis. Preincubation of HUVECs with HDL before incubation with TNF-alpha significantly suppressed the increase in the CPP32-like protease activity, preventing apoptosis in a concentration-dependent manner. These results suggest that HDL prevent the suicide pathway leading to apoptosis of endothelial cells by decreasing the CPP32-like protease activity and that HDL thus play a protective role against the "response-to-injury" hypothesis of atherogenesis. Copyright 2000 Academic Press.

Cholesterol treatment guidelines update.

PubMed

Safeer, Richard S; Ugalat, Prabha S

2002-03-01

Hypercholesterolemia is one of the major contributors to atherosclerosis and coronary heart disease in our society. The National Cholesterol Education Program of the National Institutes of Health has created a set of guidelines that standardize the clinical assessment and management of hypercholesterolemia for practicing physicians and other professionals in the medical community. In May 2001, the National Cholesterol Education Program released its third set of guidelines, reflecting changes in cholesterol management since their previous report in 1993. In addition to modifying current strategies of risk assessment, the new guidelines stress the importance of an aggressive therapeutic approach in the management of hypercholesterolemia. The major risk factors that modify low-density lipoprotein goals include age, smoking status, hypertension, high-density lipoprotein levels, and family history. The concept of "CHD equivalent" is introduced-conditions requiring the same vigilance used in patients with coronary heart disease. Patients with diabetes and those with a 10-year cardiac event risk of 20 percent or greater are considered CHD equivalents. Once low-density lipoprotein cholesterol is at an accepted level, physicians are advised to address the metabolic syndrome and hypertriglyceridemia.

Human absorption of a supplement containing purified hydroxytyrosol, a natural antioxidant from olive oil, and evidence for its transient association with low-density lipoproteins.

PubMed

González-Santiago, Maria; Fonollá, Juristo; Lopez-Huertas, Eduardo

2010-04-01

There is growing interest in the health effects of olive oil polyphenols, particularly hydroxytyrosol (HT), for their potential application in the treatment of inflammatory conditions such as cardiovascular disease (CVD). As oxidative modification of low-density lipoproteins (LDL) plays a central role in the development of CVD, natural antioxidants are a main target for the nutraceutical industry. In this study we firstly investigated the absorption of pure hydroxytyrosol (99.5%) administered as a supplement in an aqueous solution (2.5mg/kg BW) in the plasma and urine of healthy volunteers (n=10). Plasma C(max) for HT and homovanillic alcohol (HvOH) were detected at 13.0+/-1.5 and 16.7+/-2.4min, respectively. The HT and HvOH levels were undetectable 2-h after the administration. HT, HvOH, homovanillic acid and 3,4-dihydroxyphenylacetic acid were found as free forms (44%) or as glucuronide (34.4%) or sulphate (21.2%) conjugates in the 24-h urine samples of the subjects. In a second phase of the study, the same amounts of HT were administered to the subjects and the presence of HT in purified plasma lipoproteins was investigated in LDL fractions freshly isolated. 10min after the ingestion of the HT supplement, more than 50% of the total amount detected was present in the LDL-purified fractions and its concentration declined in accordance with its presence in plasma but no changes were found in total antioxidant capacity, malondialdehyde or LDL lag time. These results indicate that pure HT transiently associates with LDL lipoproteins in vivo. Copyright 2009 Elsevier Ltd. All rights reserved.

Structural Insights into High Density Lipoprotein: Old Models and New Facts

PubMed Central

Gogonea, Valentin

2016-01-01

The physiological link between circulating high density lipoprotein (HDL) levels and cardiovascular disease is well-documented, albeit its intricacies are not well-understood. An improved appreciation of HDL function and overall role in vascular health and disease requires at its foundation a better understanding of the lipoprotein's molecular structure, its formation, and its process of maturation through interactions with various plasma enzymes and cell receptors that intervene along the pathway of reverse cholesterol transport. This review focuses on summarizing recent developments in the field of lipid free apoA-I and HDL structure, with emphasis on new insights revealed by newly published nascent and spherical HDL models constructed by combining low resolution structures obtained from small angle neutron scattering (SANS) with contrast variation and geometrical constraints derived from hydrogen–deuterium exchange (HDX), crosslinking mass spectrometry, electron microscopy, Förster resonance energy transfer, and electron spin resonance. Recently published low resolution structures of nascent and spherical HDL obtained from SANS with contrast variation and isotopic labeling of apolipoprotein A-I (apoA-I) will be critically reviewed and discussed in terms of how they accommodate existing biophysical structural data from alternative approaches. The new low resolution structures revealed and also provided some answers to long standing questions concerning lipid organization and particle maturation of lipoproteins. The review will discuss the merits of newly proposed SANS based all atom models for nascent and spherical HDL, and compare them with accepted models. Finally, naturally occurring and bioengineered mutations in apoA-I, and their impact on HDL phenotype, are reviewed and discuss together with new therapeutics employed for restoring HDL function. PMID:26793109

Role of dietary supplements in lowering low-density lipoprotein cholesterol: a review.

PubMed

Nijjar, Prabhjot S; Burke, Frances M; Bloesch, Annette; Rader, Daniel J

2010-01-01

Coronary heart disease (CHD) remains a major source of morbidity and mortality. As the epidemic of obesity, diabetes, and hypertension continues to grow among young adults, the population at risk for atherosclerotic CHD is ever increasing. More than a century of laboratory and human findings link cholesterol levels with a propensity to develop atherosclerosis. Low-density lipoprotein (LDL) is the major atherogenic lipoprotein, and numerous clinical trials have shown the efficacy of lowering LDL-cholesterol (LDL-C) for reducing CHD risk. New trial data have resulted in LDL-C goals being lowered over time and expansion of the population of patients that are candidates for LDL-lowering therapy to decrease their lifetime risk of CHD. Although statins are relatively safe and well tolerated, there are still significant numbers of patients who cannot tolerate them and many others who only require mild LDL-C reduction and prefer nonprescription alternatives to statin therapy. A number of dietary supplements and functional foods have been suggested to reduce LDL-C levels, but only a few have withstood the rigors of randomized controlled trials. Here we review the evidence in support of dietary supplements and their LDL-C-lowering effects. We also review supplements that, after initial excitement about their purported effect, were not found to lower LDL-C significantly. Copyright © 2010 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Application of Fourier-transform infrared (FT-IR) spectroscopy for simple and easy determination of chylomicron-triglyceride and very low density lipoprotein-triglyceride.

PubMed

Sato, Kenichi; Seimiya, Masanori; Kodera, Yoshio; Kitamura, Akihide; Nomura, Fumio

2010-02-01

Fourier-transform infrared (FT-IR) spectroscopy is a simple and reagent-free physicochemical analysis method, and is a potential alternative to more time-consuming and labor-intensive procedures. In this study, we aimed to use FT-IR spectroscopy to determine serum concentrations of chylomicron-triglyceride (TG) and very low density lipoprotein (VLDL)-TG. We analyzed a chylomicron fraction and VLDL fraction, which had been obtained by ultracentrifugation, to search for wavelengths to designate to each fraction. Then, partial least square (PLS) calibrations were developed using a training set of samples, for which TG concentrations had been determined by conventional procedures. Validation was conducted with another set of samples using the PLS model to predict serum TG concentrations on the basis of the samples' IR spectra. We analyzed a total of 150 samples. Serum concentrations of chylomicron-TG and VLDL-TG estimated by FT-IR spectroscopy agreed well with those obtained by the reference method (r=0.97 for both lipoprotein fractions). FT-IR spectrometric analysis required 15mul of serum and was completed within 1min. Serum chylomicron-TG and VLDL-TG concentrations can be determined with FT-IR spectroscopy. This rapid and simple test may have a great impact on the management of patients with dyslipidemia. Copyright 2009. Published by Elsevier B.V.

Pharmacogenomics of high-density lipoprotein-cholesterol-raising therapies

PubMed Central

Aslibekyan, Stella; Straka, Robert J.; Irvin, Marguerite R.; Claas, Steven A.; Arnett, Donna K.

2017-01-01

High levels of HDL cholesterol (HDL-C) have traditionally been linked to lower incidence of cardiovascular disease, prompting the search for effective and safe HDL-C raising pharmaceutical agents. Although drugs such as niacin and fibrates represent established therapeutic approaches, HDL-C response to such therapies is variable and heritable, suggesting a role for pharmacogenomic determinants. Multiple genetic polymorphisms, located primarily in genes encoding lipoproteins, cholesteryl ester transfer protein, transporters and CYP450 genes have been shown to associate with HDL-C drug response in vitro and in epidemiologic studies. However, few of the pharmacogenomic findings have been independently validated, precluding the development of clinical tools that can be used to predict HDL-C response and leaving the goal of personalized medicine to future efforts. PMID:23469915

Association of low-frequency and rare coding-sequence variants with blood lipids and Coronary Heart Disease in 56,000 whites and blacks

USDA-ARS?s Scientific Manuscript database

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncerta...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lei, Dongsheng; Rames, Matthew; Zhang, Xing

Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester (CE) transfer from the atheroprotective high density lipoprotein (HDL) cholesterol to the atherogenic low density lipoprotein cholesterol. In the past decade, this property has driven the development of CETP inhibitors, which have been evaluated in large scale clinical trials for treating cardiovascular diseases. Despite the pharmacological interest, little is known about the fundamental mechanism of CETP in CE transfer. Recent electron microscopy (EM) experiments have suggested a tunnel mechanism, and molecular dynamics simulations have shown that the flexible N-terminal distal end of CETP penetrates into the HDL surface and takes up amore » CE molecule through an open pore. However, it is not known whether a CE molecule can completely transfer through an entire CETP molecule. Here, we used all-atom molecular dynamics simulations to evaluate this possibility. The results showed that a hydrophobic tunnel inside CETP is sufficient to allow a CE molecule to completely transfer through the entire CETP within a predicted transfer time and at a rate comparable with those obtained through physiological measurements. Analyses of the detailed interactions revealed several residues that might be critical for CETP function, which may provide important clues for the effective development of CETP inhibitors and treatment of cardiovascular diseases.« less

Genetic alterations affecting cholesterol metabolism and human fertility.

PubMed

DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

2014-11-01

Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

Body mass index and glycemic control influence lipoproteins in children with type 1 diabetes.

PubMed

Vaid, Shalini; Hanks, Lynae; Griffin, Russell; Ashraf, Ambika P

2016-01-01

Patients with type 1 diabetes mellitus (T1DM) have an extremely high risk of cardiovascular disease (CVD) morbidity and mortality. It is well known that dyslipidemia is a subclinical manifestation of atherosclerosis. To analyze presence and predicting factors of lipoprotein abnormalities prevalent in children with T1DM and whether race-specific differences exist between non-Hispanic white (NHW) and non-Hispanic black (NHB) in the lipoprotein characteristics. A retrospective electronic chart review including 600 (123 NHB and 477 NHW) T1DM patients aged 7.85 ± 3.75 years who underwent lipoprotein analysis. Relative to NHW counterparts, NHB T1DM subjects had a higher HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), apoB 100, lipoprotein (a), and high-density lipoprotein cholesterol (HDL-c), HDL-2, and HDL-3. Body mass index (BMI) was positively associated with TC, LDL-c, apoB 100, and non-HDL-c and inversely associated with HDL, HDL-2, and HDL-3. HbA1c was positively associated with TC, LDL-c, apoB 100, non-HDL-c, and HDL-3. Multilinear regression analysis demonstrated that HbA1c was positively associated with apoB 100 in both NHB and NHW, and BMI was a positive determinant of apoB 100 in NHW only. Poor glycemic control and high BMI may contribute to abnormal lipoprotein profiles. Glycemic control (in NHB and NHW) and weight management (in NHW) may have significant implications in T1DM. ApoB 100 concentrations in subjects with T1DM were determined by modifiable risk factors, BMI, HbA1C, and blood pressure, indicating the importance of adequate weight, glycemic, and blood pressure control for better diabetes care and likely lower CVD risk. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

PubMed Central

Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F.

2011-01-01

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743

Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians.

PubMed

Kim, Catherine; Kong, Shengchun; Krauss, Ronald M; Stanczyk, Frank Z; Reddy, Srinivasa T; Needham, Belinda L; Kanaya, Alka M

2015-12-01

Estradiol, testosterone (T), and sex hormone binding globulin (SHBG) levels are associated with lipid subfractions in men and women. Our objective was to determine if associations are independent from adipose tissue area among Asian Indians. We used data from 42 women and 57 Asian Indian men who did not use exogenous steroids or lipid-lowering medications. Lipoprotein subfractions including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed tomography. Multivariable regression models estimated the association between sex hormones with lipoprotein subfractions before and after adjustment for adiposity. Among women, lower logSHBG levels were associated with smaller logLDL particle size and higher logtriglycerides, logVLDL, and logIDL, although these associations were attenuated with adjustment for visceral adiposity in particular. Among women, lower logSHBG levels was significantly associated with lower logmedium LDL and logsmall LDL concentrations even after consideration of visceral and hepatic adiposity and insulin resistance as represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower logSHBG was also associated with smaller logLDL peak diameter size and higher logtriglycerides and logVLDL, even after adjustment for HOMA-IR and adiposity. Relationships between sex steroids and lipid subfractions were not significant among women. Among men, higher total testosterone was associated with higher logHDL and logLDL particle size, and lower logtriglycerides and logVLDL, but these associations were partially attenuated with adjustment for adiposity and HOMA-IR. Among Asian Indians, SHBG is associated with more favorable lipid subfraction concentrations, independent of hepatic and visceral fat.

A comparative clinical study of Asanadi Ghanavati and Gomutra Haritaki in Kapha Medo Margavarana (dyslipidemia)

PubMed Central

Joshi, Shivam G.; Chandola, Hari Mohan; Dave, Alankruta R.

2014-01-01

Background: Dyslipidemia is a disorder of lipoprotein metabolism, including lipoprotein overproduction or deficiency and it can be understood in the parlance of the closest conditions in Ayurveda, viz. Kapha Medo Margavarana (dyslipidemia), Atisthaulya (obesity) or Meda Roga and Prameha. Asanadi Ghanavati (AG) is a modified presentation of Asanadi Gana drugs referred in Ashtanga Hridaya and Gomutra Haritaki (GH) is described in Charaka Samhita under Shotha Chikitsa and Ashtanga Hridaya in Arsha Chikitsa. Aim: To evaluate and compare the clinical effect of AG and GH in Kapha Medo Margavarana. Materials and Methods: Patients with the high lipid profile were selected and randomly divided into two groups. In Group A (n = 30), patients were administered with tablet of AG 1 g (500 mg each) thrice a day for 8 weeks and in Group B (n = 30), tablet of GH in similar dose and duration. Effect of therapy was assessed by body circumference, Body Mass Index (BMI), cardinal symptoms like Anga-Gaurava, Bharavriddhi, etc., and lipid profile parameters. Result: AG decreased the serum cholesterol by 7.12%, Serum Triglyceride (S. TG) by 7.72%, Serum Low Density Lipoprotein (S. LDL) by 11.68%, Serum Very Low Density Lipoprotein (S. VLDL) by 7.73%, and had increased Serum High Density Lipoprotein (S. HDL) by 9.52%, with moderate improvement in 14.81% and mild improvement in 70.37% of patients. The GH decreased the serum cholesterol by 6.31%, S. TG by 9.61%, S. LDL by 12.55%, serum VLDL by 8.99%, and increased S. HDL by 10.52% with moderate improvement in 3.70%, and mild improvement in 74.07% patients. Conclusion: AG and GH are suggested to be used in Kleda Bahul Samprapti Janya Vyadhi and Ama Bahul Samprapti Janya Vyadhi respectively. PMID:25558160

Opening a New Lipid “Apo-thecary”: Incorporating Apolipoproteins as Potential Risk Factors and Treatment Targets to Reduce Cardiovascular Risk

PubMed Central

Jacobson, Terry A.

2011-01-01

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) represent the cornerstone of drug therapy to reduce low-density lipoprotein (LDL) cholesterol and cardiovascular risk. However, even optimal statin management of LDL cholesterol leaves many patients with residual cardiovascular risk, in part because statins are more effective in reducing LDL cholesterol than apolipoprotein B (Apo B). Apo B may be a better marker of atherogenic risk than LDL cholesterol because Apo B measures the total number of all atherogenic particles (total atherosclerotic burden), including LDL, very low-density lipoprotein, intermediate-density lipoprotein, remnant lipoproteins, and lipoprotein(a). To determine whether Apo B is a better indicator of baseline cardiovascular risk and residual risk after lipid therapy compared with LDL cholesterol, a MEDLINE search of the literature published in English from January 1, 1975, through December 1, 2010, was conducted. On the basis of data from most population studies, elevated Apo B was more strongly associated with incident coronary heart disease than similarly elevated LDL cholesterol. Apo B was also a superior benchmark (vs LDL cholesterol) of statins' cardioprotective efficacy in both primary-prevention and secondary-prevention trials. To minimize cardiovascular risk among persons with hypercholesterolemia or dyslipidemia, the best available evidence suggests that intensive therapy with statins should be initiated to achieve the lowest possible Apo B level (with adequate drug toleration) and then other therapies (eg, niacin, bile acid resins, ezetimibe) added to potentiate these Apo B–lowering effects. In future consensus lipid-lowering treatment guidelines, Apo B should be considered as an index of residual risk, a potential parameter of treatment efficacy, and a treatment target to minimize risk of coronary heart disease. PMID:21803958

Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans.

PubMed

Reyes-Soffer, Gissette; Moon, Byoung; Hernandez-Ono, Antonio; Dionizovik-Dimanovski, Marija; Dionizovick-Dimanovski, Marija; Jimenez, Jhonsua; Obunike, Joseph; Thomas, Tiffany; Ngai, Colleen; Fontanez, Nelson; Donovan, Daniel S; Karmally, Wahida; Holleran, Stephen; Ramakrishnan, Rajasekhar; Mittleman, Robert S; Ginsberg, Henry N

2016-01-27

Mipomersen is a 20mer antisense oligonucleotide (ASO) that inhibits apolipoprotein B (apoB) synthesis; its low-density lipoprotein (LDL)-lowering effects should therefore result from reduced secretion of very-low-density lipoprotein (VLDL). We enrolled 17 healthy volunteers who received placebo injections weekly for 3 weeks followed by mipomersen weekly for 7 to 9 weeks. Stable isotopes were used after each treatment to determine fractional catabolic rates and production rates of apoB in VLDL, IDL (intermediate-density lipoprotein), and LDL, and of triglycerides in VLDL. Mipomersen significantly reduced apoB in VLDL, IDL, and LDL, which was associated with increases in fractional catabolic rates of VLDL and LDL apoB and reductions in production rates of IDL and LDL apoB. Unexpectedly, the production rates of VLDL apoB and VLDL triglycerides were unaffected. Small interfering RNA-mediated knockdown of apoB expression in human liver cells demonstrated preservation of apoB secretion across a range of apoB synthesis. Titrated ASO knockdown of apoB mRNA in chow-fed mice preserved both apoB and triglyceride secretion. In contrast, titrated ASO knockdown of apoB mRNA in high-fat-fed mice resulted in stepwise reductions in both apoB and triglyceride secretion. Mipomersen lowered all apoB lipoproteins without reducing the production rate of either VLDL apoB or triglyceride. Our human data are consistent with long-standing models of posttranscriptional and posttranslational regulation of apoB secretion and are supported by in vitro and in vivo experiments. Targeting apoB synthesis may lower levels of apoB lipoproteins without necessarily reducing VLDL secretion, thereby lowering the risk of steatosis associated with this therapeutic strategy. Copyright © 2016, American Association for the Advancement of Science.

Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans

PubMed Central

Reyes-Soffer, Gissette; Moon, Byoung; Hernandez-Ono, Antonio; Dionizovik-Dimanovski, Marija; Jimenez, Jhonsua; Obunike, Joseph; Thomas, Tiffany; Ngai, Colleen; Fontanez, Nelson; Donovan, Daniel S.; Karmally, Wahida; Holleran, Stephen; Ramakrishnan, Rajasekhar; Mittleman, Robert S.; Ginsberg, Henry N.

2016-01-01

Mipomersen is a 20mer antisense oligonucleotide (ASO) that inhibits apolipoprotein B (apoB) synthesis; its low-density lipoprotein (LDL)–lowering effects should therefore result from reduced secretion of very-low-density lipoprotein (VLDL). We enrolled 17 healthy volunteers who received placebo injections weekly for 3 weeks followed by mipomersen weekly for 7 to 9 weeks. Stable isotopes were used after each treatment to determine fractional catabolic rates and production rates of apoB in VLDL, IDL (intermediate-density lipoprotein), and LDL, and of triglycerides in VLDL. Mipomersen significantly reduced apoB in VLDL, IDL, and LDL, which was associated with increases in fractional catabolic rates of VLDL and LDL apoB and reductions in production rates of IDL and LDL apoB. Unexpectedly, the production rates of VLDL apoB and VLDL triglycerides were unaffected. Small interfering RNA–mediated knockdown of apoB expression in human liver cells demonstrated preservation of apoB secretion across a range of apoB synthesis. Titrated ASO knockdown of apoB mRNA in chow-fed mice preserved both apoB and triglyceride secretion. In contrast, titrated ASO knockdown of apoB mRNA in high-fat–fed mice resulted in stepwise reductions in both apoB and triglyceride secretion. Mipomersen lowered all apoB lipoproteins without reducing the production rate of either VLDL apoB or triglyceride. Our human data are consistent with longstanding models of posttranscriptional and posttranslational regulation of apoB secretion and are supported by in vitro and in vivo experiments. Targeting apoB synthesis may lower levels of apoB lipoproteins without necessarily reducing VLDL secretion, thereby lowering the risk of steatosis associated with this therapeutic strategy. PMID:26819195

Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension.

PubMed

Santos, Raul D; Duell, P Barton; East, Cara; Guyton, John R; Moriarty, Patrick M; Chin, Wai; Mittleman, Robert S

2015-03-01

To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. CLINICALTRIALS.GOV: NCT00694109. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension

PubMed Central

Santos, Raul D.; Duell, P. Barton; East, Cara; Guyton, John R.; Moriarty, Patrick M.; Chin, Wai; Mittleman, Robert S.

2015-01-01

Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were −28, −27, −27, and −28%; and in apolipoprotein B −29, −28, −30, and −31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6–12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. Clinicaltrials.gov NCT00694109. PMID:24366918

Development and integration of pharmacist clinical services into the patient-centered medical home.

PubMed

Berdine, Hildegarde J; Skomo, Monica L

2012-01-01

To describe the development of pharmacist clinical services within a primary care physician practice using a standardized business plan, the extent of clinical pharmacy service integration into the patient-centered medical home (PCMH), and the clinical changes in the pharmacist's patient cohort. A two-physician primary care/occupational care practice in Pittsburgh, PA, from May 2007 to December 2011. Pharmacist-led clinic receives physician referrals for medication management, adherence, and disease management services. Pharmacist practice in a primary care setting with emphasis on integration of clinical services into the medical home model designed by the American Academy of Family Physicians. Characterization of the patient's pharmacist and services provided by the pharmacist. Glycosylated hemoglobin (A1C), body mass index (BMI), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, and blood pressure. The top five primary referral reasons were diabetes self-management, weight management, medication adherence, hypertension, and dyslipidemia management. Improvements in clinical parameters were demonstrated for lipids and A1C at 1 and 2 years after baseline. Statistically significant improvements in BMI also were observed. The pharmacist developed and integrated clinical services into a primary care practice, became an integral member of the clinical team in the two-physician PCMH, and improved patient outcomes.

Controlling for high-density lipoprotein cholesterol does not affect the magnitude of the relationship between alcohol and coronary heart disease.

PubMed

Magnus, Per; Bakke, Eirin; Hoff, Dominic A; Høiseth, Gudrun; Graff-Iversen, Sidsel; Knudsen, Gun Peggy; Myhre, Ronny; Normann, Per Trygve; Næss, Øyvind; Tambs, Kristian; Thelle, Dag S; Mørland, Jørg

2011-11-22

This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high-density lipoprotein cholesterol. In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39-0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41-0.73), after the regression model included the serum level of high-density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32-1.23) and 0.68 (0.34-1.34), respectively. Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease.

Testosterone is an independent determinant of bone mineral density in men with type 2 diabetes mellitus.

PubMed

Vasilkova, Olga; Mokhort, Tatiana; Sanec, Igor; Sharshakova, Tamara; Hayashida, Naomi; Takamura, Noboru

2011-01-01

Although many reports have elucidated pathophysiological characteristics of abnormal bone metabolism in patients with type 2 diabetes mellitus (DT2), determinants of bone mineral density (BMD) in patients with DT2 are still controversial. We examined 168 Belarussian men 45-60 years of age. Plasma total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, hemoglobin A(1c) (HbA(1c)), immunoreactive insulin, and C-reactive protein concentrations were assessed. BMD was measured using dual energy X-ray densitometry of the lumbar spine (L(1)-L(4)). Total testosterone (TT) and sex hormone-binding globulin were measured, and free testosterone (FT) was calculated. Using univariate linear regression analysis, BMD of the lumbar spine was significantly correlated with FT (r=0.32, p<0.01) and TT (r=0.36, p<0.01). Using multiple linear regression analysis adjusted for confounding factors, BMD was significantly correlated with TT (β=0.23, p<0.001) and TC (β=-0.029, p=0.005). Age (β=0.005, p=0.071), body mass index (β=0.005, p=0.053), HbA(1c) (β=-0.002, p=0.72) and duration of diabetes (β=0.001, p=0.62) were not significantly correlated with BMD. Our data indicate that androgens are independent determinants of BMD in male patients with DT2.

Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overweight and obesity more than a dietary program including low-fiber control foods.

PubMed

Maki, Kevin C; Beiseigel, Jeannemarie M; Jonnalagadda, Satya S; Gugger, Carolyn K; Reeves, Matthew S; Farmer, Mildred V; Kaden, Valerie N; Rains, Tia M

2010-02-01

Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone. Randomized, parallel-arm, controlled trial. Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations. Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy ( approximately 500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12. LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (-8.7+/-1.0 vs -4.3+/-1.1%, P=0.005). Total cholesterol (-5.4+/-0.8 vs -2.9+/-0.9%, P=0.038) and non-high-density lipoprotein-cholesterol (-6.3+/-1.0 vs -3.3+/-1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (-2.2+/-0.3 vs -1.7+/-0.3 kg, P=0.325), but waist circumference decreased more (-3.3+/-0.4 vs -1.9+/-0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group. Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference. Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

Predicting symptomatic intracerebral hemorrhage versus lacunar disease in patients with longstanding hypertension.

PubMed

Marsh, Elisabeth B; Gottesman, Rebecca F; Hillis, Argye E; Maygers, Joyce; Lawrence, Erin; Llinas, Rafael H

2014-06-01

Hypertension results in a spectrum of subcortical cerebrovascular disease. It is unclear why some individuals develop ischemia and others develop hemorrhage. Risk factors may differ for each population. We identify factors that predispose an individual to subcortical symptomatic intracerebral hemorrhage (sICH) compared with ischemia. Demographic and laboratory data were prospectively collected for hypertensive patients presenting with ischemic stroke or sICH during an 8.5-year period. Neuroimaging was retrospectively reviewed for acute (subcortical lacunes [<2.0 cm] versus subcortical sICH) and chronic (periventricular white matter disease and cerebral microbleeds) findings. We evaluated the impact of age, race, sex, serum creatinine, erythrocyte sedimentation rate, low-density lipoprotein, presence of periventricular white matter disease or cerebral microbleeds, and other factors on the risk of sICH versus acute lacune using multivariate logistic regression. Five hundred seventy-one patients had subcortical pathology. The presence of cerebral microbleeds (adjusted odds ratio [OR], 3.39; confidence interval [CI], 2.09-5.50) was a strong predictor of sICH, whereas severe periventricular white matter disease predicted ischemia (OR, 0.56 risk of sICH; CI, 0.32-0.98). This association was strengthened when the number of microbleeds was evaluated; subjects with >5 microbleeds had an increased risk of sICH (OR, 4.11; CI, 1.96-8.59). It remained significant when individuals with only cortical microbleeds were removed (OR, 1.77, CI, 1.13-2.76). An elevated erythrocyte sedimentation rate (OR, 1.19 per 10 mm/h increase; CI, 1.06-1.34) was significantly associated with sICH, whereas low-density lipoprotein was associated with ischemic infarct (OR, 0.93 risk of sICH per 10 mg/dL increase; CI, 0.86-0.99). Subclinical pathology is the strongest predictor of the nature of subsequent symptomatic event. Low-density lipoprotein and erythrocyte sedimentation rate may also have a role in risk stratification. © 2014 American Heart Association, Inc.

Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol.

PubMed

Sharma, Vineeta; Forte, Trudy M; Ryan, Robert O

2013-04-01

Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion.ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (∼150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein1's other ligand, lipoprotein lipase.

Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol

PubMed Central

Sharma, Vineeta; Forte, Trudy M.; Ryan, Robert O.

2013-01-01

Purpose of review Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Recent findings Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion. ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. Summary ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (~150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1’s other ligand, lipoprotein lipase. PMID:23241513

Cigarette smoking and its association with serum lipid/lipoprotein among Chinese nonagenarians/centenarians

PubMed Central

2012-01-01

Objective Cigarette smoking had been confirmed as an increased risk for dyslipidemia, but none of the evidence was from long-lived population. In present study, we detected relationship between cigarette smoking habits and serum lipid/lipoprotein (serum Triglyceride (TG), Total cholesterol (TC), Low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) among Chinese Nonagenarians/Centenarian. Methods The present study analyzed data from the survey that was conducted on all residents aged 90 years or more in a district, there were 2,311,709 inhabitants in 2005. Unpaired Student’s t test, χ2 test, and multiple logistic regression were used to analyze datas. Results The individuals included in the statistical analysis were 216 men and 445 women. Current smokers had lower level of TC (4.05 ± 0.81 vs. 4.21 ± 0.87, t = 2.403, P = 0.017) and lower prevalence of hypercholesteremia (9.62% vs. 15.13%, χ2 = 3.018,P = 0.049) than nonsmokers. Unadjusted and adjusted multiple logistic regressions showed that cigarette smoking was not associated with risk for abnormal serum lipid/lipoprotein. Conclusions In summary, we found that among Chinese nonagenarians/centenarians, cigarette smoking habits were not associated with increased risk for dyslipidemia, which was different from the association of smoking habits with dyslipidemia in general population. PMID:22828289

Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts.

PubMed

Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J; Hernesniemi, Jussi; Yang, Qiong; Li, Shuo; Beiser, Alexa; Larson, Martin G; Sääksjärvi, Katri; Shipley, Martin J; Singh-Manoux, Archana; Gerszten, Robert E; Wang, Thomas J; Havulinna, Aki S; Würtz, Peter; Fischer, Krista; Demirkan, Ayse; Ikram, M Arfan; Amin, Najaf; Lehtimäki, Terho; Kähönen, Mika; Perola, Markus; Metspalu, Andres; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Vasan, Ramachandran S; Kivimäki, Mika; van Duijn, Cornelia M; Seshadri, Sudha; Salomaa, Veikko

2018-06-01

Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of Ginger on Serum Lipids and Lipoproteins in Peritoneal Dialysis Patients: A Randomized Controlled Trial.

PubMed

Tabibi, Hadi; Imani, Hossein; Atabak, Shahnaz; Najafi, Iraj; Hedayati, Mehdi; Rahmani, Leila

2016-01-01

♦ In peritoneal dialysis (PD) patients, one of the major risk factors for cardiovascular disease is lipid abnormalities. This study was designed to investigate the effects of ginger supplementation on serum lipids and lipoproteins in PD patients. ♦ In this randomized, double-blind, placebo-controlled trial, 36 PD patients were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1,000 mg ginger daily for 10 weeks, while the placebo group received corresponding placebos. At baseline and at the end of week 10, 7 mL of blood were obtained from each patient after a 12- to 14-hour fast, and serum concentrations of triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and lipoprotein (a) [Lp (a)] were measured. ♦ Serum triglyceride concentration decreased significantly up to 15% in the ginger group at the end of week 10 compared with baseline (p < 0.01), and the reduction was significant in comparison with the placebo group (p < 0.05). There were no significant differences between the 2 groups in mean changes of serum total cholesterol, LDL-C, HDL-C, and Lp (a). ♦ This study indicates that daily administration of 1,000 mg ginger reduces serum triglyceride concentration, which is a risk factor for cardiovascular disease, in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

Correlation of structural stability with functional remodeling of high-density lipoproteins: the importance of being disordered.

PubMed

Guha, Madhumita; Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

2008-11-04

High-density lipoproteins (HDLs) are protein-lipid assemblies that remove excess cell cholesterol and prevent atherosclerosis. HDLs are stabilized by kinetic barriers that decelerate protein dissociation and lipoprotein fusion. We propose that similar barriers modulate metabolic remodeling of plasma HDLs; hence, changes in particle composition that destabilize HDLs and accelerate their denaturation may accelerate their metabolic remodeling. To test this notion, we correlate existing reports on HDL-mediated cell cholesterol efflux and esterification, which are obligatory early steps in cholesterol removal, with our kinetic studies of HDL stability. The results support our hypothesis and show that factors accelerating cholesterol efflux and esterification in model discoidal lipoproteins (including reduced protein size, reduced fatty acyl chain length, and/or increased level of cis unsaturation) destabilize lipoproteins and accelerate their fusion and apolipoprotein dissociation. Oxidation studies of plasma spherical HDLs show a similar trend: mild oxidation by Cu(2+) or OCl(-) accelerates cell cholesterol efflux, protein dissociation, and HDL fusion, while extensive oxidation inhibits these reactions. Consequently, moderate destabilization may be beneficial for HDL functions by facilitating insertion of cholesterol and lipophilic enzymes, promoting dissociation of lipid-poor apolipoproteins, which are primary acceptors of cell cholesterol, and thereby accelerating HDL metabolism. Therefore, HDL stability must be delicately balanced to maintain the structural integrity of the lipoprotein assembly and ensure structural specificity necessary for interactions of HDL with its metabolic partners, while facilitating rapid HDL remodeling and turnover at key junctures of cholesterol transport. The inverse correlation between HDL stability and remodeling illustrates the functional importance of structural disorder in macromolecular assemblies stabilized by kinetic barriers.

Sex differences in lipid profiles and treatment utilization among young adults with acute myocardial infarction: Results from the VIRGO study.

PubMed

Lu, Yuan; Zhou, Shengfan; Dreyer, Rachel P; Caulfield, Michael; Spatz, Erica S; Geda, Mary; Lorenze, Nancy P; Herbert, Peter; D'Onofrio, Gail; Jackson, Elizabeth A; Lichtman, Judith H; Bueno, Héctor; Spertus, John A; Krumholz, Harlan M

2017-01-01

Young women with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. An adverse lipid profile is an important risk factor for cardiovascular outcomes after AMI, but little is known about whether young women with AMI have a higher-risk lipid pattern than men. We characterized sex differences in lipid profiles and treatment utilization among young adults with AMI. A total of 2,219 adults with AMI (1,494 women) aged 18-55 years were enrolled from 103 hospitals in the United States (2008-2012). Serum lipids and lipoprotein subclasses were measured 1 month after discharge. More than 90% of adults were discharged on a statin, but less than half received a high-intensity dose and 12% stopped taking treatments by 1 month. For both men and women, the median of low-density lipoprotein (LDL) cholesterol was reduced to <100 mg/dL 1 month after discharge for AMI, but high-density lipoprotein (HDL) cholesterol remained <40 mg/dL. Multivariate regression analyses showed that young women had favorable lipoprotein profiles compared with men: women had higher HDL cholesterol and HDL large particle, but lower total cholesterol-to-HDL cholesterol ratio and LDL small particle. Young women with AMI had slightly favorable lipid and lipoprotein profiles compared with men, suggesting that difference in lipid and lipoprotein may not be a major contributor to sex differences in outcomes after AMI. In both men and women, statin remained inadequately used, and low HDL cholesterol level was a major lipid abnormality. Copyright © 2016 Elsevier Inc. All rights reserved.