... diet or exercise routine. References American Heart Association [Internet]. Dallas (TX): American Heart Association Inc.; c2017. About ... Cholesterol_UCM_001220_Article.jsp American Heart Association [Internet]. Dallas (TX): American Heart Association Inc.; c2017. Good ...
East, C.; Grundy, S.M.; Bilheimer, D.W.
Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia.
LV, Yue-Bin; YIN, Zhao-Xue; CHEI, Choy-Lye; Brasher, Melanie Sereny; ZHANG, Juan; Kraus, Virginia Byers; QIAN, Frank; SHI, Xiao-Ming; Matchar, David Bruce; ZENG, Yi
Objectives The association between cognitive function and cholesterol levels is poorly understood and inconsistent results exist among the elderly. The purpose of this study is to investigate the association of cholesterol level with cognitive performance among Chinese elderly. Design A cross-sectional study was implemented in 2012 and data were analyzed using generalized additive models, linear regression models and logistic regression models. Setting Community-based setting in eight longevity areas in China. Subjects A total of 2000 elderly aged 65 years and over (mean 85.8±12.0 years) participated in this study. Measurements Total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) concentration were determined and cognitive impairment was defined as Mini-Mental State Examination (MMSE) score≤23. Results There was a significant positive linear association between TC, TG, LDL-C, HDL-C and MMSE score in linear regression models. Each 1 mmol/L increase in TC, TG, LDL-C and HDL-C corresponded to a decreased risk of cognitive impairment in logistic regression models. Compared with the lowest tertile, the highest tertile of TC, LDL-C and HDL-C had a lower risk of cognitive impairment. The adjusted odds ratios and 95% CI were 0.73(0.62–0.84) for TC, 0.81(0.70–0.94) for LDL-C and 0.81(0.70–0.94) for HDL-C. There was no gender difference in the protective effects of high TC and LDL-C levels on cognitive impairment. However, for high HDL-C levels the effect was only observed in women. High TC, LDL-C and HDL-C levels were associated with lower risk of cognitive impairment in the oldest old (aged 80 and older), but not in the younger elderly (aged 65 to 79 years). Conclusions These findings suggest that cholesterol levels within the high normal range are associated with better cognitive performance in Chinese elderly, specifically in the oldest old. With further validation, low
... Disease Venous Thromboembolism Aortic Aneurysm More What Your Cholesterol Levels Mean Updated:Jul 5,2017 Keeping your ... stroke. This content was last reviewed April 2017. Cholesterol • Home • About Cholesterol Introduction Atherosclerosis What Your Cholesterol ...
Reimer, H.L.; Elford, R.W.; Shumak, S.
The Reflotron dry chemistry reflectance photometer was studied as a case-finding method in physicians' offices. A total of 713 adult patients had their risk factor profiles determined along with fingerprick blood cholesterol measurements. Blood cholesterol levels were classified into three categories, (<5.2 mmol/L), 51%; borderline high (5.2 to 6.1 mmol/L), 28%; and high (≥6.2 mmol/L), 21%. The physicians' predictions from clinical risk factor profiles of which patients had elevated serum cholesterol levels were inaccurate. PMID:21229051
Choudhry, Niteesh K; Patrick, Amanda R; Glynn, Robert J; Avorn, Jerry
We sought to evaluate the cost-effectiveness of applying the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial results into clinical practice. The JUPITER trial found that rosuvastatin reduces vascular events in apparently healthy subjects with elevated high-sensitivity C-reactive protein (hs-CRP) but normal low-density lipoprotein (LDL) cholesterol levels. The implications of expanding treatment recommendations based on these results have not been evaluated. We constructed a cost-effectiveness model of men ≥ 50 years and women ≥ 60 years with LDL cholesterol levels of <130 mg/dl and no known cardiovascular disease. We compared: 1) hs-CRP testing followed by rosuvastatin treatment for patients with hs-CRP levels ≥ 2.0 mg/l; and 2) usual care (i.e., no testing and no treatment). Estimates of treatment effectiveness were based on the JUPITER trial and were varied in sensitivity analyses. Among patients with LDL <130 mg/dl and hs-CRP levels ≥ 2.0 mg/l, rosuvastatin had an incremental cost-effectiveness of $25,198 per quality-adjusted life year (QALY) gained compared to usual care. If the effectiveness of rosuvastatin were 50% of that observed in JUPITER, the incremental cost-effectiveness ratio would increase to $50,871 per QALY. Implementing this strategy only in patients with a Framingham risk score ≥ 10% yielded an incremental cost-effectiveness of $14,205 per QALY. Among such intermediate-risk patients, a JUPITER-based strategy becomes cost-saving at a rosuvastatin price of < $0.86 per day. Rosuvastatin treatment for JUPITER-eligible patients appears to be cost-effective, particularly among those with a Framingham risk score ≥ 10%. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Reimer, H.L.; Elford, R.W.; Shumak, S.
To assess accuracy of blood cholesterol measurements in the office, fingerprick blood cholesterol assays by a dry reagent chemistry analyzer were compared in 151 patients with simultaneous venipuncture cholesterol assays by standard laboratory methods. Compared with the laboratory assay, seven of eight analyzers had total absolute biases less than 5%. Variability in results was comparable to that of community laboratories. PMID:21229050
Conwill, D E; Granger, D N; Cook, B H; Johnson, B B; Taylor, A E
Clinical data in neprtotic and nonnephrotic subjects were examined to help delineate the mechanism of hypercholesterolemia in nephrotic syndrome. Analyses of the relationship between total serum cholesterol and serum albumin levels and between total serum cholesterol and calculated serum oncotic pressure in 500 nonnephrotic individuals revealed strong positive correlations (r = 0.9714, p less than 0.001 and r = 0.9720, p less than 0.001, respectively). Serum beta-lipoprotein concentration was found to bear an inverse relationship to measured serum oncotic pressure in 13 nephrotic patients (r = -0.8192, p less than 0.01). Our results lend support to the thesis that serum oncotic pressure is the major governing factor in hypercholesterolemia in nephrotic syndrome.
Tao, Qing-Qing; Chen, Yan; Liu, Zhi-Jun; Sun, Yi-Min; Yang, Ping; Lu, Shen-Ji; Xu, Miao; Dong, Qin-Yun; Yang, Jia-Jun; Wu, Zhi-Ying
To determine the associations between apolipoprotein E (APOE) genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population. There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical parameters were tested. All the subjects were divided into three groups according to APOE genotypes: (1) E2/2 or E2/3 (APOE E2); (2) E3/3 (APOE E3); and (3) E2/4, E3/4, or E4/4 (APOE E4). Correlations of serum levels of glucose, total cholesterol, and triglycerides with APOE genotypes were assessed. E2, E3, and E4 allele frequencies were found to be 6.2%, 82.1%, and 11.7%, respectively. Serum levels of total cholesterol were higher in the APOE E4 group (P<0.05). A higher level of total cholesterol was associated with the E4 allele (adjusted odds ratio 1.689, 95% confidence interval 1.223-2.334, P<0.01). However, no association was found between APOE status and serum levels of glucose (adjusted odds ratio 0.981, 95% confidence interval 0.720-1.336, P=0.903) or total triglycerides (adjusted odds ratio 1.042, 95% confidence interval 0.759-1.429, P=0.800). A higher serum level of total cholesterol was significantly correlated with APOE E4 status in a cognitively normal, nondiabetic aging population. However, there was no correlation between APOE genotypes and serum levels of glucose or total triglycerides.
Tao, Qing-Qing; Chen, Yan; Liu, Zhi-Jun; Sun, Yi-Min; Yang, Ping; Lu, Shen-Ji; Xu, Miao; Dong, Qin-Yun; Yang, Jia-Jun; Wu, Zhi-Ying
Purpose To determine the associations between apolipoprotein E (APOE) genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population. Methods There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical parameters were tested. All the subjects were divided into three groups according to APOE genotypes: (1) E2/2 or E2/3 (APOE E2); (2) E3/3 (APOE E3); and (3) E2/4, E3/4, or E4/4 (APOE E4). Correlations of serum levels of glucose, total cholesterol, and triglycerides with APOE genotypes were assessed. Results E2, E3, and E4 allele frequencies were found to be 6.2%, 82.1%, and 11.7%, respectively. Serum levels of total cholesterol were higher in the APOE E4 group (P<0.05). A higher level of total cholesterol was associated with the E4 allele (adjusted odds ratio 1.689, 95% confidence interval 1.223–2.334, P<0.01). However, no association was found between APOE status and serum levels of glucose (adjusted odds ratio 0.981, 95% confidence interval 0.720–1.336, P=0.903) or total triglycerides (adjusted odds ratio 1.042, 95% confidence interval 0.759–1.429, P=0.800). Conclusion A higher serum level of total cholesterol was significantly correlated with APOE E4 status in a cognitively normal, nondiabetic aging population. However, there was no correlation between APOE genotypes and serum levels of glucose or total triglycerides. PMID:25031531
Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... A cholesterol test is done to diagnose a lipid disorder. Different experts recommend different starting ages. Recommended ...
Adu, Patrick; Ake, Edem; Agbodzakey, Hope; Adoba, Prince; Cudjoe, Obed; Agoni, Clement
Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8–28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8–38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) (p = 0.001) and high-density lipoprotein cholesterol (HDL-C) (p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6–0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05–2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP. PMID:28078142
... in 7 Obese People Has Normal Blood Pressure, Cholesterol But that doesn't mean the excess weight ... people studied, 14 percent had normal blood sugar, cholesterol and blood pressure readings, the study found. Doctors ...
Winreich, J; Pedersen, O; Dinesen, K
After the intake of approximately 24 g wheat bran daily for 5 weeks, 25 trainee nurses showed no changes in the serum levels of cholesterol, triglyceride, calcium or total 3 alpha-hydroxycholanic acid. On the other hand, the study revealed a reduced intestinal transit time with good correlation to an increased frequency of bowel movements. Average body weight fell significantly, by 0.4 kg. The daily caloric intake remained constant throughout the study period, whereas the calcium intake was significantly increased. Among the serum parameters and the dietary constituents, good correlation was found only between serum cholesterol and the dietary cholesterol content. In addition, an inverse relationship was demonstrated between the serum levels of cholesterol and total 3 alpha-hydroxycholanic acid. The significance of this observation is as yet unknown.
cardiovascular disease . All sera dissolved additional cholesterol. Sera from the hospitalized group dissolved at least as much additional cholesterol as did sera from the normal group. This finding suggests that in atherosclerosis the reserve cholesterol transport capacity is not diminished. This statement, however, must be accepted within the limitations of the method and the unknown effects of therapeutic regimens. The amount of additional cholesterol dissolved by a sample of serum is not correlated with the original concentration of cholesterol in the serum.
Martin, Mauricio; Dotti, Carlos G; Ledesma, Maria Dolores
Correct lipid homeostasis at the plasma membrane is essential for cell survival and performance. These are critically challenged in the aging brain. Changes in the levels of cholesterol, a major membrane component especially enriched in neurons, accompany the brain aging process. They also occur in neurodegenerative diseases. Understanding the causes and consequences of these changes is a crucial step when trying to delay the cognitive decline, which comes with age, or to design strategies to fight neurodegenerative disorders such as Alzheimer's disease. We here review work that has contributed to this understanding. Copyright 2010 Elsevier B.V. All rights reserved.
... Selected Audiences Contact The Health Information Center Do You Know Your Cholesterol Levels? Print-friendly Version (PDF, ... Your Heart: Get Moving and Eat Smart Did you know that high blood cholesterol is a serious ...
Zineh, Issam; Welder, Gregory J; DeBella, Amy E; Arant, Christopher B; Wessel, Timothy R; Schofield, Richard S
To investigate whether atorvastatin decreases serum or leukocyte-produced CD40 ligand (CD40L) levels and whether these effects are dependent on reduction in low-density lipoprotein cholesterol (LDL) levels in people without overt dyslipidemia. Prospective pilot study. University research center. Twenty-five normocholesterolemic volunteers (mean age 32 +/- 11 yrs; 15 women, 10 men) without cardiovascular disease. After a 2-week drug-free run-in period, subjects received atorvastatin 80 mg/day orally for 16 weeks. All lipoprotein level measurements were performed with the subject in the fasting state. The CD40L concentrations were measured by immunofluorescence detection in serum and leukocyte culture supernates after 24-hour incubation, and treatment effect was analyzed. Baseline mean +/- SD total cholesterol, LDL, high-density lipoprotein cholesterol, and triglyceride levels were 179 +/- 33, 97 +/- 29, 62 +/- 20, and 102 +/- 69 mg/dl, respectively. Mean changes in each of these levels, respectively, after 16 weeks of atorvastatin were -34%, -59%, +3%, and -23%. The median serum CD40L level was lower at 16 weeks (2.3 ng/ml, interquartile range [IQR] 1.2-5.0 ng/ml) than at baseline (3.0 ng/ml, IQR 2.1-3.7 ng/ml), but the change was not significant (p=0.24). However, atorvastatin significantly lowered CD40L produced from leukocytes by 57% (21 pg/mg of protein [IQR 10-38 pg/mg] vs 49 pg/mg [IQR 21-149 pg/mg], p=0.045). Effects were independent of reduction in cholesterol levels. Although atorvastatin did not significantly lower serum CD40L levels, significant reduction in leukocyte production was seen independent of degree of LDL reduction. These pilot data suggest a potential benefit in normocholesterolemic individuals that should be further investigated, and that leukocyte CD40L concentrations should be considered in the drug response.
... and 2013-2014, the CDC reported. Dr. David Friedman is chief of heart failure services at Long ... for cholesterol treatment, all seem to be working," Friedman said. The study was published online Nov. 30 ...
Janeesh, P A; Abraham, Annie
Cardiovascular diseases, especially atherosclerosis, have found to be the dreadful diseases worldwide and therapeutic interventions using plant sources have wide therapeutic value. Vigna unguiculata (VU) leaves have been used as food and therapeutics. Hence, our study was designed to evaluate the hypolipidemic as well as anti-atherogenic potential of VU leaves in normalizing atherogenic gene expression, cholesterol profile, generation of reactive oxygen species (ROS) and antioxidant enzyme system on cholesterol fed rabbit model. For the study New Zealand white rabbits were randomly divided into four groups of six animals each and experimental period was three months; group -i - ND [normal diet (40 g feed)], group-ii- ND (normal diet) +EAVU [ethyl acetate fraction of Vigna unguiculata (150 mg/kg body weight)], group -iii- ND [normal diet ]+ CFD [cholesterol fed diet (cholesterol 1 % of 40 g feed and cholic acid 0.5 % of 40 g feed)] and group-iv - ND [normal diet] +CFD [cholesterol fed diet ]+EAVU [ethyl acetate fraction of Vigna unguiculata (150 mg/kg body weight)]. Atherosclerosis was induced by feeding the rabbit with cholesterol (1 % of 40 g feed) and cholic acid (0.5 % of 40 g feed). Supplementation of EAVU normalized cholesterol profile, generation of reactive oxygen species (ROS), lipid peroxidation products like thiobarbituric acid reactive substance (TBARS), antioxidant system and important genes of cardiovascular diseases like interleukin-10 (IL 10), paraoxanase-1 (PON I), interleukin-6 (IL 6), and cyclooxygenase-2 (Cox 2) to near normal level as compared with normal diet. The result obtained showed the antioxidant as well as anti-atherogenic potential of Vigna unguiculata leaves in ameliorating cholesterol induced atherosclerosis, and thus it is good task to include VU leaves in daily diet for the prevention of cardiovascular diseases especially atherosclerosis.
Martínez-Carpio, P A; Barba, J; Bedoya-Del Campillo, A
A recent survey raised doubts about most of the associations between hypocholesterolemia and neuropsychiatric diseases. Nevertheless, there is scientific evidence (some very recent) that demonstrates a link between possible brain disorders and reduced levels of cholesterol. To conduct a systematic study of the literature that addresses the relation between low cholesterol levels in serum and neuropsychiatric disorders. Relevant papers were identified by means of a systematic search and selection of the literature on Medline (August 2008). The selected papers were reviewed using statistical analysis and critical-deductive reasoning. It is shown that low cholesterol levels in serum are associated and related to different neuropsychiatric disorders. Lowered cholesterol levels seem likely to be linked to higher rates of early death, suicide, aggressive and violent behaviour, personality disorders, and possibly depression, dementia and penal confinement among young males. Further studies are needed to confirm the evidence currently available and to relate more accurate diagnoses with hypocholesterolemia.
Hashimoto, Naoto; Shinomiya, Noriyuki; Saito, Katsuichi; Noda, Takahiro; Han, Kyu-Ho; Fukushima, Michihiro
We investigated the cholesterol-lowering effect of a potato ethanol residue (PER). The plasma cholesterol levels excluding high-density lipoprotein cholesterol were lower in the rats given a PER-containing diet for 6 weeks than in the control group, whereas the fecal cholesterol levels were higher. These results suggest that PER partially reduced plasma cholesterol levels via excretion of cholesterol into the feces.
Loh, K C; Tan, M H
To review the reverse cholesterol transport (RCT) model and its contribution to cholesterol catabolism in normal and disease states. Pertinent articles were identified through a MEDLINE search of the English language literature from 1983 to 1995, followed by a manual search of the bibliographies of pertinent articles. Review articles, laboratory and clinical studies and case reports. The physiology of the RCT pathway as well as alterations observed in individuals with diseases or lifestyle changes were reviewed. Data were derived mainly from laboratory studies and clinical observations. The RCT model is proposed to explain the removal of excess cholesterol from extrahepatic tissues and its delivery to liver for catabolism. This involves several regulated steps mediated by the plasma apolipoproteins and two key enzymes, lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). In essence free cholesterol in peripheral tissues is taken up by nascent high density lipoprotein (HDL) particles, converted to cholesteryl esters (by LCAT), and then transferred to apo B-containing lipoproteins (by CETP) for hepatic removal. Altered cholesterol catabolism may occur in individuals with disorders of a genetic or acquired nature as well as lifestyle changes, as a result of alterations in one of several of the putative steps or enzymes involved in RCT. The proposed antiatherogenic role of RCT remains to be validated as a review of the possible alterations noted in various disorders showed conflicting results in atherogenic propensity.
Abu-Fanne, Rami; Maraga, Emad; Abd-Elrahman, Ihab; Hankin, Aviel; Blum, Galia; Abdeen, Suhair; Hijazi, Nuha; Cines, Douglas B; Higazi, Abd Al-Roof
Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil α-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human α-defensins in their polymorphonuclear leukocytes (Def(+/+)). Accelerated Def(+/+) mice developed α-defensin·LDL complexes that accelerate the clearance of LDL from the circulation accompanied by enhanced vascular deposition and retention of LDL, induction of endothelial cathepsins, increased endothelial permeability to LDL, and the development of lipid streaks in the aortic roots when fed a regular diet and at normal plasma levels of LDL. Transplantation of bone marrow from Def(+/+) to WT mice increased LDL clearance, increased vascular permeability, and increased vascular deposition of LDL, whereas transplantation of WT bone marrow to Def(+/+) mice prevented these outcomes. The same outcome was obtained by treating Def(+/+) mice with colchicine to inhibit the release of α-defensins. These studies identify a potential new link between inflammation and the development of atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Biswas, Arundhati; Dhar, Pubali; Ghosh, Santinath
The dietary influence of sesame protein isolate (protein content 91.5%), produced from dehulled, defatted sesame meal, on blood and tissue lipid profile and lipid peroxidation has been assessed in normal and hypercholesterolemic rats. To evaluate their hypocholesterolemic and antioxidative activity in vivo, we fed 18% sesame protein isolate with or without 2% cholesterol in comparison with casein to rats for 28 d. We determined plasma total protein, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triacylglycerol as well as susceptibility of plasma and erythrocyte membrane lipid to oxidation ex vivo. Liver tissue lipid, cholesterol, phospholipids, and lipid peroxidations were also determined. The total cholesterol, LDL-cholesterol and triacylglycerol levels were significantly reduced in the sesame protein isolate and isolate containing cholesterol group than the corresponding control casein groups. HDL-cholesterol level was also increased in sesame protein isolate (41%) and protein isolate containing cholesterol group (38%) than the corresponding control casein and casein containing cholesterol groups. There was 49% and 64% lowering of plasma lipid peroxidation as well as 36% and 56% lowering of lipoprotein oxidation susceptibility (LOS) in the 2 experimental groups (sesame protein isolate and isolate containing cholesterol group) than the corresponding control (casein and casein containing cholesterol) groups. There was significant lowering of erythrocyte membrane lipid peroxidation (68% and 63% lowering in sesame protein isolate and isolate containing cholesterol groups) and liver lipid peroxidation (61% and 76% lowering in the 2 experimental groups than the corresponding control casein groups). Therefore, our results indicate that sesame protein isolate decreases cholesterol concentration in plasma, increases HDL-cholesterol, and also decreases plasma and erythrocyte membrane lipid peroxidation with or
Chan, Jeannie; Kushwaha, Rampratap S.; VandeBerg, Jane F.; VandeBerg, John L.
Partially inbred lines of laboratory opossums differ in plasma LDL cholesterol concentration and cholesterol absorption on a high cholesterol diet. The aim of the present studies was to determine whether ezetimibe inhibits cholesterol absorption and eliminates the differences in plasma cholesterol and hepatic cholesterol metabolism between high and low responders on a high cholesterol diet. Initially, we determined that the optimum dose of ezetimibe was 5 mg/kg/day, and treated six high and six low responding opossums with this dose (with equal numbers of controls) for 3 weeks while opossums consumed a high cholesterol and low fat (HCLF) diet. Plasma and LDL cholesterol concentrations decreased significantly (P<0.05) in treated but not in untreated high responding opossums. Plasma cholesterol concentrations of untreated low responders increased slightly (P<0.05) but not in treated low responders. Percent cholesterol absorption was significantly higher in untreated high responders than in other groups. Livers from high responders with or without treatment were significantly (P <0.01) heavier than livers from low responders with or without treatment. Hepatic cholesterol concentrations in untreated high responders were significantly (P<0.05) higher than in low responders with or without treatment (P<0.001). The gall bladder bile cholesterol concentrations in untreated high responders were significantly (P<0.05) lower than in other groups. A decrease in biliary cholesterol in low responders treated with ezetimibe was associated with a decrease in hepatic expression of ABCG5 and ABCG8. These studies suggest that ezetimibe decreases plasma cholesterol levels in high responders mainly by decreasing cholesterol absorption and increasing biliary cholesterol concentrations. Since ezetimibe’s target is NPC1L1 and NPC1L1 is expressed in the intestine of opossums, its effect on cholesterol absorption may be mediated by inhibiting NPC1L1 function in the intestine. PMID
Chan, Jeannie; Kushwaha, Rampratap S; Vandeberg, Jane F; Vandeberg, John L
Partially inbred lines of laboratory opossums differ in plasma low-density lipoprotein cholesterol concentration and cholesterol absorption on a high-cholesterol diet. The aim of the present studies was to determine whether ezetimibe inhibits cholesterol absorption and eliminates the differences in plasma cholesterol and hepatic cholesterol metabolism between high and low responders on a high-cholesterol diet. Initially, we determined that the optimum dose of ezetimibe was 5 mg/(kg d) and treated 6 high- and 6 low-responding opossums with this dose (with equal numbers of controls) for 3 weeks while the opossums consumed a high-cholesterol and low-fat diet. Plasma and low-density lipoprotein cholesterol concentrations decreased significantly (P < .05) in treated but not in untreated high-responding opossums. Plasma cholesterol concentrations increased slightly (P < .05) in untreated low responders but not in treated low responders. The percentage of cholesterol absorption was significantly higher in untreated high responders than in other groups. Livers from high responders with or without treatment were significantly (P < .01) heavier than livers from low responders with or without treatment. Hepatic cholesterol concentrations in untreated high responders were significantly (P < .05) higher than those in low responders with or without treatment (P < .001). The gall bladder bile cholesterol concentrations in untreated high responders were significantly (P < .05) lower than those in other groups. A decrease in biliary cholesterol in low responders treated with ezetimibe was associated with a decrease in hepatic expression of ABCG5 and ABCG8. These studies suggest that ezetimibe decreases plasma cholesterol levels in high responders mainly by decreasing cholesterol absorption and increasing biliary cholesterol concentrations. Because ezetimibe's target is NPC1L1 and NPC1L1 is expressed in the intestine of opossums, its effect on cholesterol absorption may be mediated
Myant, N B
This review includes a brief account of the routes of entry of cholesterol into the plasma by (a) secretion of lipoproteins and (b) uptake of tissue free cholesterol by lipoproteins in the interstitial fluid, the metabolic transformation undergone by cholesterol within the plasma, with particular reference to the esterification of plasma free cholesterol by lecithin:cholesteryl acyltransferase and the redistribution of esterified cholesterol from high-density to low-density and very-low-density lipoprotein, and the routes by which cholesterol is removed from the plasma by bulk transport. The review end with a balance sheet showing the approximate amounts of cholesterol entering and leaving the plasma by different routes.
De Biase, Simone Grigoletto; Fernandes, Sabrina Francine Carrocha; Gianini, Reinaldo José; Duarte, João Luiz Garcia
Compare levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) among vegetarians and omnivores. Blood samples were collected from 76 individuals--both males and females--separated in four different diet groups: omnivores, lacto-ovo vegetarians, lacto vegetarians, and restricted vegetarians (or vegans). Dosing was done for: TC, LDL, HDL and TG. Significant difference was reported for TC, LDL and TG levels among the samples. Higher levels were reported by omnivores, with decreased levels for vegetarians as animal products were restricted, with lowest levels having been reported by vegans. Mean and standard deviation for TC were 208.09 +/- 49.09 mg/dl in the group of omnivores, and 141.06 +/- 30.56 mg/dl in the group of vegans (p < 0.001). LDL values for omnivores and vegans were respectively: 123.43 +/- 42.67 mg/dl and 69.28 +/- 29.53 mg/dl (p < 0.001). As for TG, those values were 155.68 +/- 119.84 mg/dl and 81.67 +/- 81.90 mg/dl (p < 0.01). As for HDL level no difference was reported between the samples, but HDL/TC ratio was significantly higher in vegans (p = 0.01). Vegetarian diet was associated to lower levels of TG, TC and LDL as compared to the diet of omnivores.
Pereira, Miria Gomes; Visbal, Gonzalo; Salgado, Leonardo T.; Vidal, Juliana Cunha; Godinho, Joseane L. P.; De Cicco, Nuccia N. T.; Atella, Geórgia C.; de Souza, Wanderley; Cunha-e-Silva, Narcisa
Trypanosoma cruzi epimastigotes store high amounts of cholesterol and cholesteryl esters in reservosomes. These unique organelles are responsible for cellular digestion by providing substrates for homeostasis and parasite differentiation. Here we demonstrate that under nutritional lipid stress, epimastigotes preferentially mobilized reservosome lipid stocks, instead of lipid bodies, leading to the consumption of parasite cholesterol reservoirs and production of ergosterol. Starved epimastigotes acquired more LDL-NBD-cholesterol by endocytosis and distributed the exogenous cholesterol to their membranes faster than control parasites. Moreover, the parasites were able to manage internal cholesterol levels, alternating between consumption and accumulation. With normal lipid availability, parasites esterified cholesterol exhibiting an ACAT-like activity that was sensitive to Avasimibe in a dose-dependent manner. This result also implies that exogenous cholesterol has a role in lipid reservoirs in epimastigotes. PMID:26068009
Pereira, Miria Gomes; Visbal, Gonzalo; Salgado, Leonardo T; Vidal, Juliana Cunha; Godinho, Joseane L P; De Cicco, Nuccia N T; Atella, Geórgia C; de Souza, Wanderley; Cunha-e-Silva, Narcisa
Trypanosoma cruzi epimastigotes store high amounts of cholesterol and cholesteryl esters in reservosomes. These unique organelles are responsible for cellular digestion by providing substrates for homeostasis and parasite differentiation. Here we demonstrate that under nutritional lipid stress, epimastigotes preferentially mobilized reservosome lipid stocks, instead of lipid bodies, leading to the consumption of parasite cholesterol reservoirs and production of ergosterol. Starved epimastigotes acquired more LDL-NBD-cholesterol by endocytosis and distributed the exogenous cholesterol to their membranes faster than control parasites. Moreover, the parasites were able to manage internal cholesterol levels, alternating between consumption and accumulation. With normal lipid availability, parasites esterified cholesterol exhibiting an ACAT-like activity that was sensitive to Avasimibe in a dose-dependent manner. This result also implies that exogenous cholesterol has a role in lipid reservoirs in epimastigotes.
... to write your own questions for the next time you see your healthcare provider. For example: How can I reduce my cholesterol? How often should I have my cholesterol checked? ©2015, American Heart Association Multi-language Fact Sheet Topics Heart-related Conditions What is ...
Mitschelen, J.J.; St. Clair, R.W.; Hester, S.H.
The purpose of this study was to determine whether the free cholesterol of hypercholesterolemic low density lipoprotein from cholesterol-fed nonhuman primates has a greater potential for surface transfer to cell membranes than does the free cholesterol of normal low density lipoprotein. The low density lipoproteins were isolated from normal and hypercholesterolemic rhesus and cynomolgus monkeys, incubated with membranes from Acholeplasma laidlawii, a mycoplasma species devoid of cholesterol in its membranes, and the mass transfer of free cholesterol determined by measuring membrane cholesterol content. Since these membranes neither synthesize nor esterify cholesterol, nor degrade the protein or cholesterol ester moieties of low density lipoprotein, they are an ideal model with which to study differences in the cholesterol transfer potential of low density lipoprotein independent of the uptake of the intact low density lipoprotein particle. These studies indicate that, even though there are marked differences in the cholesterol composition of normal and hypercholesterolemic low density lipoproteins, this does not result in a greater chemical potential for surface transfer of free cholesterol. Consequently, if a difference in the surface transfer of free cholesterol is responsible for the enhanced ability of hypercholesterolemic low density lipoprotein to promote cellular cholesterol accumulation and, perhaps, also atherosclerosis, it must be the result of differences in the interaction to the hypercholesterolemic low density lipoprotein with the more complicated mammalian cell membranes, rather than differences in the chemical potential for cholesterol transfer.
Darwish, Deya S.; Wang, Desheng; Konat, Gregory W.; Schreurs, Bernard G.
Cholesterol and sulfatides play many important roles in learning and memory. To date, our observations about the effects of cholesterol on learning have been assessed during response acquisition i.e., the learning of a new memory. Here we report for the first time on the effect of a cholesterol diet on a previously formed memory. Rabbits were given trace conditioning of the nictitating membrane response for ten days, then fed a 2% cholesterol diet for eight weeks, and then assessed for memory recall of the initially learned task. We show that dietary cholesterol had an adverse effect on memory recall. Second, we investigated whether dietary cholesterol caused an increase in brain cholesterol and sulfatide levels in four major brain structures (hippocampus, frontal lobe, brainstem, and cerebellum) using a technique for analyzing myelin and myelin-free fractions separately. Although our data confirm previous findings that dietary cholesterol does not directly affect cholesterol and establish that it does not affect sulfatide levels in the brain, these levels did increase rather significantly in the hippocampus and frontal lobe as a function of learning and memory. PMID:20141286
Xie, Jiang; Guan, Fei; Wang, Jia-Hong; Hu, Da-Yi
The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects. Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire, some of which were about basic knowledge of lipids. About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P < 0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P < 0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P < 0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels. Management of hypercholesterolemia should be an important component of health strategy in Beijing. Education is imperative for residents as well as for physicians.
Iser, D J; Avera, K
This study was performed to see if there was any difference in cholesterol levels between three socioeconomic groups of Bougainvillian males, each with different levels of exposure to western influences. Serum cholesterol levels were measured in 50 subjects from each of 1) village people leading a traditional lifestyle, 2) town dwellers exposed to western influences, and 3) mine workers who regularly dined in the company mess. Mean cholesterol levels were significantly higher in the mine workers (5.3 +/- SD 0.9 mmol/l) and the town dwellers (4.8 +/- SD 0.8 mmol/l) than in the village people (3.7 +/- SD 1.0 mmol/l). There was a positive correlation between serum cholesterol level and age in two groups, the town dwellers and the village people, even though the latter group had a low mean cholesterol level. There was a significant correlation between body mass index (BMI) and serum cholesterol level for the entire group as well as the town dwellers and mine workers. The higher mean cholesterol levels in the mine workers and town dwellers than in the village people may reflect a difference in lifestyle, particularly in diet, between these groups, and may represent an increased risk for ischaemic heart disease.
Bitzur, Rafael; Cohen, Hofit; Kamari, Yehuda; Harats, Dror
Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.
Vanstone, C A.; Raeini-Sarjaz, M; Jones, P J.H.
Although plant sterols are known to suppress intestinal cholesterol absorption, whether plasma and hepatic lipid levels are influenced through non-gut related internal mechanisms has not been established. To examine this question 50 male hamsters were divided into 5 groups and fed semi-purified diets containing 20% energy as fat and 0.25% (w/w) cholesterol ad libitum for 60 days. The control group (i) received diet alone, while four additional groups consumed the diet plus one of four equivalent phytosterol mixtures (5 mg/kg/day) given either as (ii) tall oil phytosterols/stanols mixed with diet (oralSA), (iii) tall oil phytosterols/stanols subcutaneously injected (subSA), (iv) soybean oil phytosterols alone mixed with diet (oralSE), or (v) soybean oil subcutaneous injected phytosterols alone (subSE). The control group and both orally supplemented groups also received placebo subcutaneous sham injections. Neither food consumption, body weight, nor liver weight differed across treatment groups. Subcutaneous administration of SA and SE decreased plasma total cholesterol levels by 21% and 23% (p < 0.0001) and non-apolipoprotein-A cholesterol concentrations by 22% and 15% (p < 0.0002), respectively, compared to control. HDL cholesterol and TG concentrations remained unchanged across all groups, except for a decline of 25% (p < 0.0001) in HDL concentration in the subSE group versus control. Plasma campesterol levels were lower (p < 0.05) in the subSA group relative to all other groups. Plasma campesterol:cholesterol and campesterol:sitosterol ratios were, however, higher (p < 0.0001) for both the oral and subSE groups. Hepatic cholesterol levels were higher (p < 0.0001) in the oral and subSE phytosterol groups by 30% and 31%, respectively, relative to control. We conclude that low doses of subcutaneously administered plant sterols reduce circulating cholesterol levels through mechanisms other than inhibiting intestinal cholesterol absorption.
Song, M; Park, S; Lee, H; Min, B; Jung, S; Park, S; Kim, E; Oh, S
We investigated the probiotic properties of Lactobacillus acidophilus NS1, such as acid resistance, bile tolerance, adherence to HT-29 cells, and cholesterol assimilation activity. In an animal study, 7-wk-old male C57BL/6 mice were fed a normal diet, a high-fat diet (HFD), or an HFD with L. acidophilus NS1 (ca. 1.0×10(8) cfu/mL) for 10 wk. Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly lower in mice fed an HFD with L. acidophilus NS1 than in those fed an HFD only, whereas high-density lipoprotein cholesterol levels were similar between these 2 groups. To understand the mechanism of the cholesterol-lowering effect of L. acidophilus NS1 on the HFD-mediated increase in plasma cholesterol levels, we determined mRNA levels of genes involved in cholesterol homeostasis in the liver. Expression of sterol regulatory element-binding protein 2 (Srebp2) and LDL receptor (Ldlr) in the liver was dramatically reduced in mice fed a HFD compared with those fed a normal diet. When L. acidophilus NS1 was administered orally to HFD-fed mice, an HFD-induced suppression of Srebp2 and Ldlr expression in the liver was abolished. These results suggest that the oral administration of L. acidophilus NS1 to mice fed an HFD increased the expression of Srebp2 and Ldlr in the liver, which was inhibited by high fat intake, thus leading to a decrease in plasma cholesterol levels. Lactobacillus acidophilus NS1 could be a useful probiotic microorganism for cholesterol-lowering dairy products and the improvement of hyperlipidemia and hepatic lipid metabolism. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Frank, E; Winkleby, M; Fortmann, S P; Rockhill, B; Farquhar, J W
This article examines cholesterol-related knowledge, cholesterol-related behaviors, and plasma cholesterol levels in 12-24-year-olds, using data collected from four community-based cross-sectional surveys conducted 1979-1980, 1981-1982, 1985-1986, and 1989-1990. Participants included 1,552 individuals from randomly sampled households in two control cities (San Luis Obispo and Modesto, California) of the Stanford Five-City Project. Over the eleven-year study period, cholesterol-related knowledge improved in both control cities (P < .0002). Cholesterol-related behavior (P < .0003) and plasma cholesterol levels (P < .002) significantly improved only in San Luis Obispo (a college city with more 19-24-year-olds and a better-educated population than Modesto). In general, knowledge and behavior scores and plasma cholesterol levels were lower in these 12-24-year-olds than in 25-74-year-olds, although trends at all ages were similar over time and by demographic variables. Although the cholesterol-related interventions that began in the mid-1980s primarily targeted adults, these 12-24-year-olds' cholesterol-related knowledge improved (as did, to a lesser extent, their cholesterol-related behavior and plasma cholesterol levels). These findings have implications for upcoming youth-related cholesterol interventions.
Gibaldi, M; Kradjan, W
The purpose of this review is to provide perspective on the developments leading to the recognition of high cholesterol levels as a risk factor for coronary heart disease (CHD). Another objective is to consider the unfolding controversies regarding the relative value of cholesterol-lowering drug therapy in primary and secondary prevention. Should physicians use lipid-lowering drugs to treat patients with elevated cholesterol levels but no clinical evidence of coronary disease, or limit intervention to patients with a previous history of angina, coronary angioplasty, coronary artery bypass surgery, or myocardial infarction? This review finds inadequate data to support a recommendation for screening large populations for the presence of elevated cholesterol levels or for primary prevention in those known to have high cholesterol. On the other hand, there is mounting evidence to support vigorous intervention in those with known coronary disease. Further study is needed to determine whether a subset of patients with one or more well-defined risk factors would benefit from primary prevention.
Cho, Kyung Hoon; Jeong, Myung Ho; Ahn, Youngkeun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Seung, Ki Bae; Park, Seung Jung
The relation between low-density lipoprotein (LDL) cholesterol levels and clinical outcomes after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has not been described. A total of 9,571 eligible patients (mean age 62.6 ± 12.5 years, 6,967 men) who underwent PCI with a final diagnosis of AMI from the Korea Acute Myocardial Infarction Registry (KAMIR) were divided into 5 groups according to LDL cholesterol level: < 70, 70 to 99, 100 to 129, 130 to 159, and ≥ 160 mg/dl. Clinical outcomes in hospital and 1 and 12 months after PCI in patients with AMI were examined. Age and co-morbidities decreased as LDL cholesterol increased. Patients with higher LDL cholesterol levels had favorable hemodynamic status and laboratory findings. Lifesaving medications, including lipid-lowering drugs, were underused in patients with lower LDL cholesterol levels. Clinical outcomes in hospital and 1 and 12 months after PCI showed better results as LDL cholesterol increased, except for patients with LDL cholesterol levels ≥ 160 mg/dl. In a Cox proportional-hazards model, LDL cholesterol level was not an independent predictor of mortality at 12 months, after adjusting for clinical characteristics including demographics and biologic data. In conclusion, the cholesterol paradox in patients with AMI is related to confounding by baseline characteristics associated with survival. More intensive treatment including lipid-lowering therapy for AMI in patients with lower LDL cholesterol level may result in better clinical outcomes.
Lemhadri, A; Hajji, L; Michel, J-B; Eddouks, M
The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Carum carvi L. fruits at a dose of (20mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats (STZ). After a single oral administration, Carum carvi extract produced a significant decrease on triglycerides levels in normal rats (p<0.05). In STZ diabetic rats, cholesterol levels were decreased significantly 6h after Carum carvi treatment (p<0.05). On the other hand, repeated oral administration of Carum carvi extract exhibited a significant hypotriglyceridemic and hypocholesterolemic activities in both normal (p<0.01 and <0.001 respectively) and STZ diabetic rats (p<0.001) 15 days after Carum carvi treatment. We conclude that the aqueous extract of Carum carvi (20mg/kg) exhibits a potent lipid lowering activity in both normal and severe hyperglycemic rats after repeated oral administration of Carum carvi aqueous extract.
Revis, N W; McCauley, P; Bull, R; Holdsworth, G
The effects of drinking water containing 2 or 15 ppm chlorine (pH 6.5 and 8.5), chlorine dioxide, and monochloramine on thyroid function and plasma cholesterol were studied because previous investigators have reported cardiovascular abnormalities in experimental animals exposed to chlorinated water. Plasma thyroxine (T4) levels, as compared to controls, were significantly decreased in pigeons fed a normal or high-cholesterol diet and drinking water containing these drinking water disinfectants at a concentration of 15 ppm (the exception was chlorine at pH 6.5) for 3 months. In most of the treatment groups, T4 levels were significantly lower following the exposure to drinking water containing the 2 ppm dose. Increases in plasma cholesterol were frequently observed in the groups with lower T4 levels. This association was most evident in pigeons fed the high-cholesterol diet and exposed to these disinfectants at a dose of 15 ppm. For example, after 3 months of exposure to deionized water or water containing 15 ppm monochloramine, plasma cholesterol was 1266 +/- 172 and 2049 +/- 212 mg/dl, respectively, a difference of 783 mg/dl. The factor(s) associated with the effect of these disinfectants on plasma T4 and cholesterol is not known. We suggest however that these effects are probably mediated by products formed when these disinfectants react with organic matter in the upper gastrointestinal tract. PMID:3456597
... from the food you eat (such as eggs, meats, and dairy products). Too much cholesterol can have ... fewer foods with saturated fats (such as red meat and most dairy products). Opt for healthier fats, ...
Dubland, Joshua A.; Francis, Gordon A.
Unregulated cellular uptake of apolipoprotein B-containing lipoproteins in the arterial intima leads to the formation of foam cells in atherosclerosis. Lysosomal acid lipase (LAL) plays a crucial role in both lipoprotein lipid catabolism and excess lipid accumulation as it is the primary enzyme that hydrolyzes cholesteryl esters derived from both low density lipoprotein (LDL) and modified forms of LDL. Evidence suggests that as atherosclerosis progresses, accumulation of excess free cholesterol in lysosomes leads to impairment of LAL activity, resulting in accumulation of cholesteryl esters in the lysosome as well as the cytosol in foam cells. Impaired metabolism and release of cholesterol from lysosomes can lead to downstream defects in ATP-binding cassette transporter A1 regulation, needed to offload excess cholesterol from plaque foam cells. This review focuses on the role LAL plays in normal cholesterol metabolism and how the associated changes in its enzymatic activity may ultimately contribute to atherosclerosis progression. PMID:25699256
Revis, N.W.; McCauley, P.; Bull, R.; Holdsworth, G.
The effects of drinking water containing 2 or 15 ppm chlorine (pH 6.5 and 8.5), chlorine dioxide, and monochloramine on thyroid function and plasma cholesterol were studied because previous investigators have reported cardiovascular abnormalities in experimental animals exposed to chlorinated water. Plasma thyroxine (T4) levels, as compared to controls, were significantly decreased in pigeons fed a normal or high-cholesterol diet and drinking water containing these drinking water disinfectants at a concentration of 15 ppm (the exception was chlorine at pH 6.5) for 3 months. In most of the treatment groups, T4 levels were significantly lower following the exposure to drinking water containing the 2 ppm dose. Increase in plasma cholesterol were frequently observed in the groups with lower T4 levels. This association was most evident in pigeons fed the high-cholesterol diet and exposed to these disinfectants at a dose of 15 ppm. The factor(s) associated with the effect of these disinfectants on plasma T4 and cholesterol is not known. The authors suggest however that these effects are probably mediated by products formed when these disinfectants react with organic matter in the upper gastrointestinal tract.
Berryman, Claire E; Fleming, Jennifer A; Kris-Etherton, Penny M
Background: Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function.Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes.Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants (n = 48) and in normal-weight (body mass index: <25; n = 14) and overweight or obese (≥25; n = 34) participants by using linear mixed models.Results: The almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-β-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL (P < 0.05). No diet effects were observed in the overweight or obese group.Conclusions: Substituting almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable
Denimal, Damien; Pais de Barros, Jean-Paul; Petit, Jean-Michel; Bouillet, Benjamin; Vergès, Bruno; Duvillard, Laurence
Phospholipids and sphingolipids are major components of HDL. They play a critical role in HDL functionality and protective effects against atherosclerosis. As HDL are dysfunctional in type 1 diabetic patients, we ascertained whether they presented abnormalities in their phospholipid and sphingolipid profile, despite normal HDL cholesterol concentration. Using liquid chromatography-tandem mass spectrometry, we quantified the main species of phosphatidylcholines, sphingomyelins, lysophophatidylcholines, phosphatidylethanolamines, phosphatidylinositols, ceramides, plasmalogens and sphingosines 1-phosphate in the HDL2 and HDL3 from 54 type 1 diabetic patients and 50 controls. Serum HDL cholesterol was similar in the 2 groups of subjects. When data were expressed relative to the total amount of phospholipids and sphingolipids, sphingosines-1-phosphate (S1P) were 11.7% (NS) and 14.4% (p = 0.0062) lower in HDL2 and HDL3, respectively, from type 1 diabetic patients than from controls. Ceramides were 23% (p = 0.005) and 24% (borderline significance) lower in HDL2 and HDL3, respectively. The concentration of apolipoprotein M, the carrier of S1P, was similar in patients and controls. In type 1 diabetic patients compared to controls, the concentration of d18:1-S1P, the main S1P species, was decreased in total plasma (-17.0%, p < 0.0001), HDL fraction (-21.9%, p < 0.0001) and non-HDL fraction (-13.7%, p = 0.012). The concentration of ceramides was decreased in total plasma (-24.4%, p < 0.0001), HDL fraction (-27.9%, p = 0.0006) and non-HDL fraction (-22.0%, p = 0.0087). Despite normal HDL cholesterol level, the phospholipid + sphingolipid profile is impaired in HDL from type 1 diabetic patients. These abnormalities, especially the decrease in S1P, could contribute to the impaired HDL functionality observed in these patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Ríos-Lugo, María J; Cano, Pilar; Jiménez-Ortega, Vanesa; Fernández-Mateos, María P; Scacchi, Pablo A; Cardinali, Daniel P; Esquifino, Ana I
Melatonin effect on body weight progression, mean levels and 24-hr pattern of circulating adiponectin, leptin, insulin, glucose, triglycerides and cholesterol were examined in rats fed a normal or a high-fat diet. In experiment 1, rats fed a normal diet were divided into two groups: receiving melatonin (25 μg/mL drinking water) or vehicle for 9 wk. In experiment 2, animals were divided into three groups: two fed with a high-fat diet (35% fat) and melatonin (25 μg/mL) or vehicle in drinking water for 11 wk, while a third group was given a normal diet (4% fat). At the end of experiments, groups of eight rats were killed at six different time intervals throughout a 24-hr period. Melatonin administration for 9 wk decreased body weight gain from the 3rd wk on without affecting food intake. A significant reduction in circulating insulin, glucose and triglyceride mean levels and disrupted daily patterns of plasma adiponectin, leptin and insulin were observed after melatonin. In high fat-fed rats, melatonin attenuated body weight increase, hyperglycemia and hyperinsulinemia, as well as the increase in mean plasma adiponectin, leptin, triglycerides and cholesterol levels. The high-fat diet disrupted normal 24-hr patterns of circulating adiponectin, insulin and cholesterol, the effects on insulin and cholesterol being counteracted by melatonin. Nocturnal plasma melatonin concentration in control and obese rats receiving melatonin for 11 wk attained values 21-24-fold greater than controls. The results indicate that melatonin counteracts some of the disrupting effects of diet-induced obesity in rats. © 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.
Bangalore, Sripal; Fayyad, Rana; Kastelein, John J; Laskey, Rachel; Amarenco, Pierre; DeMicco, David A; Waters, David D
The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether percent low-density lipoprotein cholesterol (LDL-C) reduction or attained LDL-C levels add incremental prognostic value to statin dose is not known. Patients in the Treating to New Targets (TNT), Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL), and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials (patient-level data) randomized to a statin arm (atorvastatin 80 mg/10 mg or simvastatin 20 mg) were chosen. Patients were divided into groups based on attained LDL-C levels (≤70 vs >70 mg/dL) and percent LDL-C reduction (≥50% vs <50%). Primary outcome was major cardiovascular event defined as death due to coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. Incremental prognostic value was assessed by using a forward conditional Cox proportional hazards model. Two models were tested: Model 1: Step 1 statin dose; Step 2 add attained LDL-C levels (continuous variable); Step 3 add percent LDL-C reduction (continuous variable). Model 2: Steps 2 and 3 were reversed. Among 13,937 patients included in this study, percent LDL-C reduction added incremental prognostic value over both statin dose and attained LDL-C levels (global chi-square increased from 3.64 to 26.1 to 47.5; P <.0001). However, attained LDL-C level did not provide incremental prognostic value over statin dose and percent LDL-C reduction (global chi-square increased from 3.64 to 47.5 to 47.5; P <.0001 and .94, respectively). Among patients with attained LDL-C ≤70 mg/dL, those with percent LDL-C reduction of <50% had a significantly higher risk of primary outcome (hazard ratio [HR], 1.51; 95% confidence interval [CI
Elias, P M; Williams, M L; Maloney, M E; Bonifas, J A; Brown, B E; Grayson, S; Epstein, E H
The pathological scaling in recessive x-linked ichthyosis is associated with accumulation of abnormal quantities of cholesterol sulfate in stratum corneum (J. Clin. Invest. 68:1404-1410, 1981). To determine whether or not cholesterol sulfate accumulates in recessive x-linked ichthyosis as a direct result of the missing enzyme, steroid sulfatase, we quantitated both steroid sulfatase and its substrate, we quantitated both steroid sulfatase and its substrate, cholesterol sulfate, in different epidermal strata, as well as within stratum corneum subcellular fractions obtained from normal human and neonatal mouse epidermis and from patients with recessive x-linked ichthyosis. In normal human and mouse epidermis, steroid sulfatase activity peaked in the stratum granulosum and stratum corneum, and negligible activity was detectable in lower epidermal layers. In contrast, in recessive x-linked ichthyosis epidermis, enzyme levels were virtually undetectable at all levels. In normal human stratum corneum, up to 10 times more steroid sulfatase activity was present in purified peripheral membrane preparations than in the whole tissue. Whereas in normal human epidermis cholesterol sulfate levels were lowest in the basal/spinous layer, and highest in the stratum granulosum, in recessive x-linked ichthyosis the levels were only slightly higher in the lower epidermis, but continued to climb in the stratum corneum. In both normal and in recessive x-linked ichthyosis stratum corneum, cholesterol sulfate appeared primarily within membrane domains, paralleling the pattern of steroid sulfatase localization. Finally, the role of excess cholesterol sulfate in the pathogenesis of recessive x-linked ichthyosis was directly tested by topical applications of this substance, which produced visible scaling in hairless mice in parallel to an increased cholesterol sulfate content of the stratum corneum. These results demonstrate an intimate relationship between steroid sulfatase and cholesterol
Banu, Shaheena; Jabir, Nasimudeen R; Manjunath, Nanjappa C; Firoz, C K; Kamal, Mohammad A; Khan, Mohammad S; Tabrez, Shams
The present study compares the role and significance of non-high density lipoproteins (non-HDL) cholesterol level in pre-diabetic and diabetic patients. This study also compares non-HDL cholesterol level between males and females and with different age groups as well. An observational study was conducted among 3830 randomly selected individuals to envisage the association of non-HDL cholesterol and other lipid parameters with age, gender, and diabetic status. On the basis of health status, the subjects were classified as diabetic, pre-diabetic and normal. Fasting blood samples were collected and analyzed on Roche p-800 modular system. Total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL) and fasting triglycerides were also measured. From the above mentioned parameters, the level of non-HDL cholesterol level was also calculated. Significant association was observed with non-HDL cholesterol level and all other studied lipid parameters (total cholesterol, HDL, LDL and triglycerides) compared with age and gender of the subjects studied. Moreover, the calculated non-HDL level, total cholesterol and triglycerides were found to be significantly co-related with diabetic status of the patients involved in the study. However, HDL and LDL values did not show any significant association with diabetic status of the patients. In this study, we found that age and gender of the studied subjects are associated with non-HDL cholesterol. Moreover, our data clearly indicates the positive association of non-HDL cholesterol level with pre-diabetic and diabetic status of the patients. Based on our study, we recommend estimation of non-HDL level in routine clinical practice to differentiate pre-diabetic and diabetic patients.
National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.
Studies have shown that high blood cholesterol levels play a role in the development of coronary heart disease in adults, and that the process leading to atherosclerosis begins in childhood. To address the problem of high cholesterol levels in children, the Panel on Blood Cholesterol Levels recommends complementary approaches for individuals and…
National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.
Studies have shown that high blood cholesterol levels play a role in the development of coronary heart disease in adults, and that the process leading to atherosclerosis begins in childhood. To address the problem of high cholesterol levels in children, the Panel on Blood Cholesterol Levels recommends complementary approaches for individuals and…
Valensia, Rosy; Masulili, Sri Lelyati C.; Lessang, Robert; Radi, Basuni
Coronary heart disease (CHD) is an abnormal narrowing of heart arteries associated with local accumulation of lipids, in the form of cholesterol and triglycerides. Periodontal disease is a chronic inflammatory that suggests link to the development of CHD. In periodontitis have been reported changes in lipid profile, include increased of cholesterol levels of blood. Objective: to analyse correlation between blood cholesterol level with periodontal status of CHD and non CHD subjects. Methods: Periodontal status and blood cholesterol level of 60 CHD and 40 non CHD subjects was measured. Result: Blood cholesterol level in CHD subjects differs from non CHD subjects (p=0.032). Blood cholesterol level correlates with pocket depth (p=0.003) and clinical attachment loss (CAL) (p=0.000) in CHD subjects. Blood cholesterol level correlates with pocket depth (p=0.010) in non CHD subjects. There is no significant correlation between blood cholesterol level and bleeding on probing (BOP) in CHD subjects. There is no significant correlation between blood cholesterol level with BOP and CAL in non CHD subjects. Conclusion: Blood cholesterol level in control group is higher than CHD patients. Blood cholesterol level positively associated with pocket depth (r=0.375) and CAL (r=0.450) in CHD patients. Blood cholesterol level is positively associated with pocket depth (r=0.404) in control group.
Ramírez-Expósito, María Jesús; Arrazola, Marcelina; Carrera-González, María Pilar; Arias de Saavedra, José Manuel; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, José Manuel
The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension. Also, AVP has vasoconstrictor, mitogenic, hyperplasic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Furthermore, cholesterol blood levels are also associated with hypertension, although the underlying mechanism is not known. Here we analyze the relationship between blood total cholesterol levels and serum vasopressin- degrading cystyl-aminopeptidase activity (AVP-DA) in healthy humans, and the differences between men and women. Linear correlation coefficients were calculated to test relationships between AVP-DA and blood total cholesterol levels. Sex differences were observed for AVP-DA, being this activity higher in men than in women. According to the linear model of the regression analysis, AVP-DA showed a significant negative correlation with blood total cholesterol levels in men, whereas no correlation was observed in women. Several studies in humans demonstrate the existence of greater plasma AVP concentrations in normal men compared to normal women, which could explain the gender-differences observed in the present work in relation with AVP-DA. However, AVP-DA is related to blood cholesterol levels only in men, although in our hands, women showed higher blood cholesterol levels than men. This could indicate that the risk of high cholesterol-related hypertension is more probable in men than in women. Although AVP-DA misregulation could be involved in the pathogenesis of hypertension, its relation with cholesterol levels appears only in men, but not in women.
Hahm, Sahng-Wook; Park, Jieun; Son, Yong-Suk
The Opuntia humifusa stem (OHSt) contains high levels of antioxidants including vitamin C, flavonoids, and polyphenols that may prove beneficial in treating diabetes mellitus. The objective of this study was to examine the hypothesis that intake of the OHSt regulates blood glucose levels and hypolipidemic responses in rats with diabetes mellitus induced by injection of streptozotocin. Forty Sprague-Dawley rats (6 weeks of age) were assigned to 5 groups: normal control, rats with streptozotocin-induced diabetes mellitus (DM), DM treated with OHSt 150 mg/kg per day, DM treated with OHSt 250 mg/kg per day, and DM treated with OHSt 500 mg/kg per day. Powdered OHSt was suspended in distilled water and administered orally through the sonde once daily. After 7 weeks of treatment, the fasting blood glucose and triglyceride levels of the OHSt groups were significantly lower when compared with the DM group (P < .05). Treatment with the OHSt also resulted in a significant decrease in serum total cholesterol and low-density lipoprotein cholesterol (P < .05). Decreases in both total cholesterol and low-density lipoprotein cholesterol were accompanied by a significant increase in serum high-density lipoprotein cholesterol (P < .05). Furthermore, levels of alanine aminotransferase and aspartate aminotransferase were significantly lower in the OHSt groups than in the DM group (P < .05). In addition, a significant increase in relative beta cell volume of pancreas was observed in rats treated with 500 mg/kg of OHSt when compared with the untreated DM rats (P < .05). The overall results suggest that the OHSt possesses potential hypoglycemic and hypolipidemic activity in streptozotocin-induced diabetic rats. Copyright © 2011 Elsevier Inc. All rights reserved.
Jian, Zhi-Hong; Chiang, Yi-Chen; Lung, Chia-Chi; Ho, Chien-Chang; Ko, Pei-Chieh; Ndi Nfor, Oswald; Chang, Hui-Chin; Liaw, Yi-Ching; Liang, Yu-Chiu; Liaw, Yung-Po
The present study assessed the effects of vegetarian and omnivorous diets on HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), TAG and the ratio of HDL-C to total cholesterol (TC) by gender. HDL-C, LDL-C, TAG and HDL-C:TC were compared among three diet groups (vegan, ovo-lacto vegetarian and omnivorous). Multivariate linear regression analysis was performed to examine factors significantly and independently associated with vegetarian status and to estimate the β value of lipid profiles for the diet groups. Settings A cross-sectional study. Data were obtained from the Taiwanese Survey on the Prevalence of Hyperglycemia, Hyperlipidemia and Hypertension (TwSHHH). The study comprised included 3257 men and 3551 women. After adjusting for confounders, vegan and ovo-lacto vegetarian diets lowered LDL-C levels (β=-10.98, P=0.005 and β=-7.12, P=0.025, respectively) in men compared with omnivorous diet. There was a significant association between HDL-C and vegan diet (β=-6.53, P=0.004). In females, the β values of HDL-C, TAG and HDL-C:TC were -5.72 (P<0.0001), 16.51 (P=0.011) and -0.02 (P=0.012) for vegan diet, and -4.86 (P=0.002), 15.09 (P=0.008) and -0.01 (P=0.026) for ovo-lacto vegetarian diet, when compared with omnivorous diet. Vegan diet was associated with lower HDL-C concentrations in both males and females. Because the ovo-lacto vegetarian diet was effective in lowering LDL-C, it may be more appropriate for males.
de Bem, Andreza Fabro; Portella, Rafael de Lima; Colpo, Elisângela; Duarte, Marta Maria Medeiros Frescura; Frediane, Andressa; Taube, Paulo Sergio; Nogueira, Cristina Wayne; Farina, Marcelo; da Silva, Edson Luiz; Teixeira Rocha, João Batista
Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group--regular chow; Cholesterol group--1% cholesterol-enriched diet; diphenyl diselenide group--regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group--the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral delta-aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.
Aptekmann, Nancy P; Cesar, Thais B
This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. The sample consisted of 103 men (18-66 y) and 26 women (18-65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet.
Background This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. Methods The sample consisted of 103 men (18–66 y) and 26 women (18–65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Results Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (−11%, p <0.001), LDL-cholesterol (−18%, p < 0.001), apolipoprotein B (apo B) (−12%, p < 0.01) and LDL/HDL ratio (−12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (−5%, p <0.02), LDL-cholesterol (−12%, p <0.03), apolipoprotein B (−12%, p <0.01) and LDL/HDL ratio (−16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Conclusion Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet. PMID:23919812
Sparling, Phillip B.; Snow, Teresa K.; Beavers, Bill D.
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…
Sparling, Phillip B.; Snow, Teresa K.; Beavers, Bill D.
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…
Aubin, M.; Godin, G.; Vézina, L.; Maziade, J.; Desharnais, R.
OBJECTIVE: To assess whether knowing blood cholesterol test results influences people's intention to lower their dietary fat intake and to assess changes in diet after 3 months. DESIGN: Randomized clinical study. SETTING: Two hospital-based family medicine centres. PARTICIPANTS: A total of 526 patients aged 18 to 65, without prior knowledge of their blood cholesterol levels, were recruited. Seventy did not appear for their appointments, and 37 did not meet study criteria, leaving 419 participants. From that group, 391 completed the study. INTERVENTIONS: Patients submitted to cholesterol screening were randomly assigned to one of two groups, completing the study questionnaires either before (control group) or after (experimental group) being informed of their screening test results. All participants were called 3 months after transmission of test results to assess their dietary fat intake at that time. MAIN OUTCOME MEASURES: Differences in intention to adopt a low-fat diet reported between the experimental and control groups and differences in dietary fat intake modification after 3 months between patients with normal and abnormal blood cholesterol test results. RESULTS: Knowledge of test results influenced patients' intentions to adopt low-fat diets (F1,417 = 5.4, P = .02). Patients reported lower mean dietary fat intake after 3 months than at baseline (P < .0001). The reduction was greater in patients with abnormal screening results (F2,388 = 3.6, P = .03). CONCLUSIONS: Being informed of personal blood cholesterol levels effects an immediate change in eating habits that translates into reduced dietary fat intake. PMID:9640523
Slowing, K; Ganado, P; Sanz, M; Ruiz, E; Tejerina, T
Garlic is known for its pharmacologic and nutritional properties. In previous studies, garlic elicited a reduction in plasma levels of lipids by inhibiting hepatic cholesterol synthesis. The aim of this study was to investigate in an in vivo model the effects of garlic extract and some fractions on cholesterol levels and vascular reactivity in cholesterol-fed rats. Rats were fed a cholesterol-enriched diet for 16 wk and were divided into 10 groups as follows: control and hypercholesterolemic diet groups, 4 groups fed frozen garlic fractions and 4 groups fed raw garlic fractions with different doses. Blood samples were obtained to analyze HDL and LDL cholesterol levels. After treatment, rats were killed. The heart, liver and kidneys were weighed; the aorta was isolated, mounted in organ chambers and vascular reactivity was tested. Plasma concentration of cholesterol was 58 mg/dL (100%) at the beginning of the study and increased to 102 mg/dL (153%; hypercholesterolemic group) at the end of the treatment. Plasma total cholesterol decreased in all groups treated with garlic; moreover, this effect was higher in rats fed raw garlic fractions and extracts. LDL decreased significantly with respect to the hypercholesterolemic group in all groups treated with garlic fractions and extracts (P: < 0.01); however, an increase in HDL was found in those treated with frozen fractions and extracts. The liver:body weight ratio decreased in all treated groups. The relaxing effect of acetylcholine (ACh) was enhanced in arteries contracted with noradrenaline (NE). These data suggest that garlic fractions could prevent diet-induced hypercholesterolemia and vascular alterations in the endothelium-dependent relaxation associated with atherosclerosis.
Huang, Zhenhua; Liang, Lining; Li, Lingyu; Xu, Miao; Li, Xiang; Sun, Hao; He, Songwei; Lin, Lilong; Zhang, Yixin; Song, Yancheng; Yang, Man; Luo, Yuling; Loh, Horace H; Law, Ping-Yee; Zheng, Dayong; Zheng, Hui
Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.
Zalesskaya, G. A.; Laskina, O. V.; Mitkovskaya, N. P.; Kirkovsky, V. V.
We have studied the effect of extracorporeal ultraviolet blood irradiation on cholesterol metabolism in patients with cardiovascular diseases. We have carried out a comprehensive analysis of the spectral characteristics of blood and plasma, gas-exchange and oximetry parameters, and the results of a complete blood count and chemistry panel before and after UV blood irradiation. We have assessed the changes in concentrations of cholesterols (total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides) in the blood of the patients in response to a five-day course of UV blood irradiation. The changes in the spectral characteristics of blood and plasma, the chemistry panel, the gas composition, and the fractional hemoglobin composition initiated by absorption of UV radiation are used to discuss the molecular mechanisms for the effect of therapeutic doses of UV radiation on blood cholesterols.
LEMKE, Michael K.; APOSTOLOPOULOS, Yorghos; HEGE, Adam; WIDEMAN, Laurie; SÖNMEZ, Sevil
Long-haul truck drivers in the United States experience elevated cardiovascular health risks, possibly due to hypercholesterolemia. The current study has two objectives: 1) to generate a cholesterol profile for U.S. long-haul truck drivers; and 2) to determine the influence of work organization characteristics and sleep quality and duration on cholesterol levels of long-haul truck drivers. Survey and biometric data were collected from 262 long-haul truck drivers. Descriptive analyses were performed for demographic, work organization, sleep, and cholesterol measures. Linear regression and ordinal logistic regression analyses were conducted to examine for possible predictive relationships between demographic, work organization, and sleep variables, and cholesterol outcomes. The majority (66.4%) of drivers had a low HDL (<40 mg/dL), and nearly 42% of drivers had a high-risk total cholesterol to HDL cholesterol ratio. Sleep quality was associated with HDL, LDL, and total cholesterol, and daily work hours were associated with LDL cholesterol. Workday sleep duration was associated with non-HDL cholesterol, and driving experience and sleep quality were associated with cholesterol ratio. Long-haul truck drivers have a high risk cholesterol profile, and sleep quality and work organization factors may induce these cholesterol outcomes. Targeted worksite health promotion programs are needed to curb these atherosclerotic risks. PMID:28049935
Lemke, Michael K; Apostolopoulos, Yorghos; Hege, Adam; Wideman, Laurie; Sönmez, Sevil
Long-haul truck drivers in the United States experience elevated cardiovascular health risks, possibly due to hypercholesterolemia. The current study has two objectives: 1) to generate a cholesterol profile for U.S. long-haul truck drivers; and 2) to determine the influence of work organization characteristics and sleep quality and duration on cholesterol levels of long-haul truck drivers. Survey and biometric data were collected from 262 long-haul truck drivers. Descriptive analyses were performed for demographic, work organization, sleep, and cholesterol measures. Linear regression and ordinal logistic regression analyses were conducted to examine for possible predictive relationships between demographic, work organization, and sleep variables, and cholesterol outcomes. The majority (66.4%) of drivers had a low HDL (<40 mg/dL), and nearly 42% of drivers had a high-risk total cholesterol to HDL cholesterol ratio. Sleep quality was associated with HDL, LDL, and total cholesterol, and daily work hours were associated with LDL cholesterol. Workday sleep duration was associated with non-HDL cholesterol, and driving experience and sleep quality were associated with cholesterol ratio. Long-haul truck drivers have a high risk cholesterol profile, and sleep quality and work organization factors may induce these cholesterol outcomes. Targeted worksite health promotion programs are needed to curb these atherosclerotic risks.
Hecht, Harvey S
The emergence of atherosclerosis imaging, using coronary calcium scanning (CAC) and carotid intima media thickness (CIMT) and plaque as stronger predictors of cardiovascular events than risk factors of atherosclerosis, has created a paradigm shift in the primary prevention of cardiovascular disease. Rather than population-derived indices to define normal or abnormal low-density lipoprotein (or other lipid values) in the untreated individual patient, it is more appropriate to define "normal" as "cholesterol values at which level there is no subclinical atherosclerosis" and "abnormal" as "cholesterol values at which level there is subclinical atherosclerosis," with the severity of "abnormal" depending on the degree of subclinical atherosclerosis. Similarly, the low-density lipoprotein treatment goal is the level at which atherosclerosis progression is halted. Extension of the subclinical atherosclerosis risk-based paradigms to primary prevention trials dramatically changes the manner in which trials should be conducted in the future, as well as the results of trials already performed. For example, asymptomatic patients with a CAC score of 0 have an extraordinarily low event rate but have been included in primary prevention statin trials even though their risk without treatment is very small. Reanalysis of the statin primary prevention trials after excluding the percentage (40%) of patients who would be expected to have a CAC score of 0 yields an absolute risk increase of 60% in both the placebo group (from 5.4% to 8.5%), and the statin group (from 3.0% to 4.8%). Absolute risk reduction increased by 58% (from 2.4% to 3.8%). Relative risk reduction of 44% was unchanged. In conclusion, 1) the presence or absence of atherosclerosis as measured by CAC redefines normal or abnormal lipid levels in an individual patient; 2) statin absolute risk reduction is significantly greater than previously appreciated; and 3) patients with a CAC score of 0 should be excluded from
Rosa-Bray, M; Wisdom, C; Wada, S; Johnson, BR; Grifols-Roura, V; Grifols-Lucas, V
Background and Objectives LDL apheresis is used to treat patients with familial hypercholesterolaemia, and low-volume plasmapheresis for plasma donation may similarly lower cholesterol levels in some donors. This study was designed to assess the effect of plasmapheresis on total, LDL and HDL cholesterol levels in a plasma donor population. Materials and Methods This was a prospective, unblinded longitudinal cohort study in which a blood sample was obtained for analysis before each donation. Data from 663 donors were analysed using a multivariable repeated measures regression model with a general estimating equations approach with changes in cholesterol as the primary outcome measure. Results The model predicted a significant decrease in total and LDL cholesterol for both genders and all baseline cholesterol levels (P < 0·01). The greatest total cholesterol decreases (women, −46·8 mg/dL; men, −32·2 mg/dL) were associated with high baseline levels and 2–4 days between donations. Small but statistically significant increases (P ≤ 0·01) in HDL cholesterol were predicted for donors with low baseline levels. Conclusions These results suggest that, in donors with elevated baseline cholesterol levels, total and LDL cholesterol levels may decrease during routine voluntary plasmapheresis. PMID:23517282
Raju, K; Vijayan, E
Circulating plasma cholesterol levels were measured in conscious ovariectomized rats, bearing an indwelling silastic catheter in the external jugular vein, after intravenous (i.v.) pulse injection of 100 microliter 0.9% NaCl containing varying doses of neurotensin and/or substance P. Control injections of saline or decapeptide LH-RH or phosphate buffer did not modify plasma cholesterol levels. 10 or 20 micrograms doses of neurotensin produced a significant and dose-related increase in plasma cholesterol levels while similar doses of substance P had an opposite effect and induced a significant decline in plasma cholesterol levels in ovariectomized rats. 4-APP, a drug which selectively inhibits hepatic secretion of lipoproteins, significantly lowers plasma cholesterol to levels comparable to those produced by substance P. 4-APP and substance P induced hypocholesterolemia was readily reversed by a single dose of neurotensin. These findings indicate that neurotensin acts to increase circulating cholesterol levels and substance P antagonizes this hypercholesterolemic effect of neurotensin presumably by acting at some step in cholesterol transport. Reversal of the inhibitory effects of 4-APP and substance P on blood cholesterol by neurotensin may be through its action on hepatic secretion of lipoproteins, since 4-APP is known to lower circulating cholesterol by its specific action on hepatic secretion of lipoproteins.
Kuwabara, Tomoko; Han, Kyu-Ho; Hashimoto, Naoto; Yamauchi, Hiroaki; Shimada, Ken-Ichiro; Sekikawa, Mitsuo; Fukushima, Michihiro
We examined the effects of different types of buckwheat sprouts on the plasma cholesterol concentration, fecal steroid excretion and hepatic mRNA expression related to cholesterol metabolism in rats. Rats were fed a cholesterol-free diet with 5 g of Kitawasesoba common buckwheat sprout powder (KS)/100 g, 5 g of Hokkai T no. 8 tartary buckwheat sprout powder (HS-8)/100 g or 5 g of Hokkai T no. 9 tartary buckwheat sprout powder (HS-9)/100 g of diet for 4 wk. Control rats were fed a diet with alpha-cornstarch instead of sprout powder for 4 wk. There were no significant differences in food intake, body weight, liver weight or cecal contents among the groups. Plasma total cholesterol concentrations in the HS-8 and HS-9 groups were significantly lower than in the control group, whereas there was no significant difference between the KS and control groups. Fecal bile acid excretion and cecal short-chain fatty acid concentrations in the KS, HS-8 and HS-9 groups were significantly greater than in the control group. Furthermore, fecal matter excretion in the KS, HS-8 and HS-9 groups tended to be increased compared to the control group, with that in the HS-8 group being significantly higher than in the control group. Hepatic cholesterol 7alpha-hydroxylase mRNA expression in the KS, HS-8 and HS-9 groups and hepatic HMG-CoA reductase mRNA expression in the HS-9 group were significantly higher than in the control group. The results suggest that tartary buckwheat sprout powder has a serum cholesterol-lowering function by enhancing fecal bile acid excretion through increased fecal matter excretion or the upregulation of hepatic cholesterol 7alpha-hydroxylase mRNA expression in rats.
Croft, J B; Cresanta, J L; Webber, L S; Srinivasan, S R; Freedman, D S; Burke, G L; Berenson, G S
Fasting serum lipids, lipoprotein cholesterol, and other cardiovascular disease risk factors were examined in 321 natural parents of children with low and/or high levels of beta- and pre-beta-lipoprotein cholesterol. Parents of children from low pre-beta-lipoprotein groups had elevated alpha- and lower pre-beta-lipoprotein cholesterol levels. Parents whose children had high beta-lipoprotein cholesterol levels also had high serum total and beta-lipoprotein cholesterol levels. Parents of children with high levels of both beta- and pre-beta-lipoprotein cholesterol had a high prevalence of both abnormal risk factor levels, as well as clinical evidence of early coronary artery disease (before age 50 years). These observations show that parents of children with high beta- and/or pre-beta-lipoprotein cholesterol levels have greatly enhanced risk for cardiovascular disease, and children mirror their parents' lipoprotein cholesterol levels. These observations emphasize the need for cardiovascular risk evaluation early in life, especially in high-risk families.
Coleman, Chris A.; Friedman, Alice G.; Burright, Richard G.
Investigates the relationship between daily life events and total cholesterol levels among high school students (N=104) and examines contributions of health-related behaviors. Analyses showed that scores on a scale of daily life events explained a significant portion of variance in cholesterol levels. Females reported a greater degree of negative…
Sim, J S; Bragg, D B
Effects of dietary lipid factors (saturated and unsaturated oil, cholesterol and plant sterols) on the serum and egg yolk cholesterol levels of the laying hen were investigated. Single Comb White Leghorn laying hens, at thirty weeks of age, were used in two trials by feeding two basal diets containing 8.0% hydrogenated coconut oil or safflower oil, with or without supplemental cholesterol (1.0%), soysterols (2.0%) or combinations of both. Safflower oil, per se, had a superior property to hydrogenated coconut oil in suppressing cholesterol levels, in both serum and egg yolk. Cholesterol supplementation to the safflower oil basal diet resulted in a significant (P less than 0.01) elevation of serum and egg yolk cholesterol levels, whereas cholesterol in combination with hydrogenated coconut oil did not change the serum level. Cholesterol lowering effect of soysterols was clearly demonstrated in both serum and egg yolk by feeding soysterols alone as well as by feeding soysterols in combination with cholesterol.
Gunasegaram, Saranya; Jayathilake, Chathuni; Weththasinghe, Pabodha; Jayawardana, Barana Chaminda; Vidanarachchi, Janak Kamil
Hypocholesterolaemic and hypoglycaemic effect of banana blossom were studied in high-cholesterol fed rats. Experimental groups were fed for 4 weeks, with casein as the basal diet (CN), in comparison with two diets containing 0.5% cholesterol (CD) and 0.5% cholesterol + 21% banana blossom powder (CDB). Serum total cholesterol, non-HDL-cholesterol level, and serum glucose concentrations were lower in CDB fed group compared with CD fed group. Lower serum cholesterol and glucose level (P < 0.05) in CDB fed group were followed by higher faecal weight, caecal weight, caecal Lactobacilli, and Bifidobacteria population in CDB fed group compared to CD diet fed group. Lower serum AST level in banana blossom fed rats showed the reduction in oxidative stress induced by high cholesterol diet. Based on these data, it could be speculated that banana blossom incorporated experimental diets may modulate the hypocholesterolaemic and hypoglycaemic responses in Wistar rats. PMID:28042480
Hall, Danika V
Earlier this year, two industry-sponsored advertising campaigns for cholesterol awareness that target the general public were launched in Australia. These campaigns aimed to alert the public to the risks associated with having high cholesterol and encouraged cholesterol testing for wider groups than those specified by the National Heart Foundation. General practitioners should be aware of the potential for the two campaigns to confuse the general public as to who should be tested, and where. The campaign sponsors (Unilever Australasia and Pfizer) each have the potential to benefit by increased market share for their products, and increased profits. These disease awareness campaigns are examples of what is increasingly being termed "condition branding" by pharmaceutical marketing experts.
Serum cholesterol fasting concentrations were measured in 280 male homicidal offenders. Those with an antisocial personality or an intermittent explosive disorder with a habitually violent tendency in both when under the influence of alcohol showed a lower mean level of serum cholesterol than did other offenders. The results were also compatible with the hypotheses that antisocial personality consists of two groups. The exact reason for the finding is not clear but it could be connected with an enhanced insulin secretion.
Steiner, R D; Linck, L M; Flavell, D P; Lin, D S; Connor, W E
The Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by a deficiency of the enzyme 7-dehydrocholesterol Delta(7)-reductase. This enzyme converts 7-dehydrocholesterol (7-DHC) to cholesterol in the last step in cholesterol biosynthesis. The pathology of this condition may result from two different factors: the deficiency of cholesterol itself and/or the accumulation of precursor sterols such as 7-DHC. Although cholesterol synthesis is defective in cultured SLOS cells, to date there has been no evidence of decreased whole body cholesterol synthesis in SLOS and only incomplete information on the synthesis of 7-DHC and bile acids. In this first report of the sterol balance in SLOS, we measured the synthesis of cholesterol, other sterols, and bile acids in eight SLOS subjects and six normal children. The diets were very low in cholesterol content and precisely controlled. Cholesterol synthesis in SLOS subjects was significantly reduced when compared with control subjects (8.6 vs. 19.6 mg/kg per day, respectively, P < 0.002). Cholesterol precursors 7-DHC, 8-DHC, and 19-nor-cholestatrienol were synthesized in SLOS subjects (7-DHC synthesis was 1.66 +/- 1.15 mg/kg per day), but not in control subjects. Total sterol synthesis was also reduced in SLOS subjects (12 vs. 20 mg/kg per day, P < 0.022). Bile acid synthesis in SLOS subjects (3.5 mg/kg per day) did not differ significantly from control subjects (4.6 mg/kg per day) and was within the range reported previously in normals. Normal primary and secondary bile acids were identified. This study provides direct evidence that whole body cholesterol synthesis is reduced in patients with SLOS and that the synthesis of 7-DHC and other cholesterol precursors is profoundly increased. It is also the first reported measure of daily bile acid synthesis in SLOS and provides evidence that bile acid supplementation is not likely to be necessary for treatment. These sterol balance studies
Nanda, Sunil Kumar; Bharathy, M; Dinakaran, Asha; Ray, Lopamudra; Ravichandran, K
One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values. To evaluate the correlation of Friedewalds calculated LDL with direct LDL method. We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20-70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P < 0.05. Pearsons correlation formula was used to test the correlation between direct LDL values with Friedewald's formula. There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl. This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method.
Junqueira, Juliana C; Mancini, Maria N G; Carvalho, Yasmin R; Anbinder, Ana Lia; Balducci, Ivan; Rocha, Rosilene F
The purpose of this study was to evaluate the effects of simvastatin on guided bone regeneration in the mandibles of ovariectomized rats, and to observe their blood cholesterol levels. Seventy female rats were divided into two groups: control and treated, both groups containing normal and ovariectomized rats. A month after ovariectomy a bone defect was created in the mandible, and was covered by a polytetrafluoroethylene membrane. The treated groups received simvastatin orally for 15 or 30 days. The rats were sacrificed 15, 30 or 60 days after surgery, at which time a blood sample was extracted for blood cholesterol level analysis and the mandible was extracted for densitometric, histological and morphometric analysis. All specimens underwent analysis of variance. The ovariectomized animals had higher cholesterol levels than the treated normal animals, and no significant difference was found between the different treatment periods and the sacrifice times. The densitometric, histological and morphometric analysis showed that the treated ovariectomized animals developed more new bone than the control ovariectomized rats, but no significant difference was observed between the treatment periods. It can be concluded that the deficiency of estrogen increased the level of blood cholesterol and that the simvastatin aided new bone formation in the ovariectomized animals.
Cheng, Susan; Lichtman, Judith H; Amatruda, Joan M; Smith, Grace L; Mattera, Jennifer A; Roumanis, Sarah A; Krumholz, Harlan M
Little is known about the extent to which patients are aware of nationally-recommended cholesterol and lipid subfraction targets. The authors interviewed 738 patients hospitalized with coronary artery disease to assess their knowledge of their low-density lipoprotein, high-density lipoprotein, and total cholesterol levels as well as corresponding national targets. Only 8%, 8%, and 43% of patients could recall their low-density lipoprotein, high-density lipoprotein, and total cholesterol values, respectively. Only 5%, 2%, and 50% could correctly name targets for these values. Knowledge of cholesterol targets was particularly poor among women, nonwhites, and patients without any college education. Patients with multiple cardiac risk factors and patients with a previous history of cardiovascular disease were no more knowledgeable about their cholesterol targets than those without these conditions. These findings suggest that current cholesterol education efforts appear inadequate, particularly for women, nonwhites, and patients without any college education.
Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P
The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.
Looney, Marilyn A.; Rimmer, James H.
Reports a study that examined the effects of a 15-week aerobic activity program on high school students' cholesterol levels. Analysis of control and participating students indicated that there were significant reductions in total cholesterol in the training group. There were no significant differences between groups in high density lipoprotein…
Looney, Marilyn A.; Rimmer, James H.
Reports a study that examined the effects of a 15-week aerobic activity program on high school students' cholesterol levels. Analysis of control and participating students indicated that there were significant reductions in total cholesterol in the training group. There were no significant differences between groups in high density lipoprotein…
Kostara, Christina E; Tsimihodimos, Vasilis; Elisaf, Moses S; Bairaktari, Eleni T
Recent studies suggest that the cholesterol content of HDL (high density lipoproteins) may provide limited information on their antiatherogenic properties and that the composition and particles' structure provide more information on their functionality. We used NMR-based (nuclear magnetic resonance-based) lipidomics to study the relationships of serum HDL-C (HDL-cholesterol) levels with the lipid composition of HDL particles in three groups of subjects selected on the basis of their HDL-C levels. Subjects with low and high HDL-C levels exhibited differences in HDL lipidome compared to those with normal HDL-C levels. In pattern recognition analysis, the discrimination power among all groups was of high significance. The low HDL-C group presented enrichment of the core in triglycerides and depletion in cholesterol esters, whereas the high HDL-C group showed a decrease in triglycerides content. Additionally, as HDL-C increases, all lipid classes are esterified with higher percentage of unsaturated than saturated fatty acids. In addition to the aforementioned differences, the surface layer is enriched in sphingomyelin and free cholesterol in the high HDL-C level group. NMR-based lipidomic analysis of HDL can be particularly useful since it provides insights into molecular features and helps in the characterization of the atheroprotective function of HDL lipoproteins and in the identification of novel biomarkers of cardiovascular risk.
Varady, Krista A; Jones, Peter J H
At present, dyslipidemia is most commonly treated with drug therapy. However, because safety concerns regarding the use of pharmaceutical agents have arisen, a need for alternative nonpharmacological therapies has become increasingly apparent. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) recommends lifestyle therapies, which include a combination of diet and exercise modifications, in place of drug treatment for patients who fall into an intermediate range of coronary heart disease (CHD) risk. This review examined the cholesterol lowering efficacy of the following 2 NCEP-recommended combination therapies: 1) low saturated fat diets combined with exercise, and 2) nutritional supplementation, i.e., fish oil, oat bran, or plant sterol supplementation, combined with exercise, in the treatment of dyslipidemia. Combination therapies are particularly advantageous because diet and exercise elicit complementary effects on lipid profiles. More specifically, diet therapies, with some exceptions, lower total (TC) and LDL cholesterol (LDL-C) concentrations, whereas exercise interventions increase HDL cholesterol (HDL-C) while decreasing triglyceride (TG) levels. With respect to specific interventions, low saturated fat diets combined with exercise lowered TC, LDL-C, and TG concentrations by 7-18, 7-15, and 4-18%, respectively, while increasing HDL-C levels by 5-14%. Alternatively, nutritional supplements combined with exercise, decreased TC, LDL-C, and TG concentrations by 8-26, 8-30, and 12-39%, respectively, while increasing HDL-C levels by 2-8%. These findings suggest that combination lifestyle therapies are an efficacious, preliminary means of improving cholesterol levels in those diagnosed with dyslipidemia, and should be implemented in place of drug therapy when cholesterol levels fall just above the normal range.
Reiber, I; Gógl, A
The predominate number of homozygote familial hypercholesterolemic and approximately 20% of heterozygotes are resistant to low cholesterol diet and lipid lowering pharmacological treatment even in combination of 2 or more drugs. In such cases, the selective lipoprotein apheresis has become a promising alternative and indicated absolute (homozygotes) or relative (heterozygotes). The combination of low density lipoprotein apheresis, together with diet and drugs, should allow a maximal lowering of low density lipoprotein-cholesterol (-60-70%). Besides low density lipoprotein, various apheresis procedures may also eliminate other potentially atherogenic factors, such as lipoprotein(a) and fibrinogen and acutely improve the haemo-rheological status of the patient. The authors review several lipoprotein apheresis procedures with varying degrees of selectivity, those have and furthermore analysis the advantages and disadvantages and cost of each procedure.
Lannon, C M; Earp, J
The American Academy of Pediatrics, concerned that pediatric cholesterol screening may lead to mislabeling and overly restrictive diets, stresses laboratory confirmation and nutritional follow-up for children with elevated cholesterol levels. Parents' behavior and attitudes toward screening children for high cholesterol were studied. During an 8-week period in summer of 1989 all children 2 through 15 years of age seen for well-child examinations at a community pediatric group practice were offered cholesterol screening by finger-stick method. Most parents were well-educated and white. Of 439 children screened, 134 (31%) had cholesterol levels above the recommended cutoff point of 175 mg/dL (75th percentile). Only 63 children returned for confirmatory lipid panels; parents of children who did not return were interviewed. Reasons for noncompliance included "not sure test machine was accurate" (67%); "child too traumatized by finger stick" (47%); and "will try low-cholesterol diet before recheck" (40%). A third of these parents believed that confirmation of an elevated cholesterol level "would make the child worry too much." Only 29% of these parents talked with a dietician. In this middle-class, well-educated population, a large proportion of children had elevated screening cholesterol values, but few complied with American Academy of Pediatrics guidelines. As a result, many children may be mislabeled as hypercholesterolemic and may not benefit from screening.
Bulum, T; Kolaric, B; Duvnjak, L
Previous studies have suggested a positive association between dyslipidemia and chronic kidney disease, but sparse data are available on the relation of lipids and urinary albumin excretion rate (UAE) in normoalbuminuric patients with normal renal function. The aim of this study was to evaluate the associations of serum lipids, including total, LDL, HDL, HDL2, HDL3 cholesterol, and triglyceride levels with UAE in normoalbuminuric Type 1 diabetic (T1D) patients. Study included 313 normoalbuminuric T1D patients with normal renal function and before any interventions with statins, ACE inhibitors or angiotensin II receptor blockers. Subjects were classified as low-normoalbuminuric (UAE<11.0 mg/24h) or high-normoalbuminuric (UAE≥11.0 mg/24h) based on median UAE of at least two 24- h urine collections. Correlations and multiple linear regressions analysis were performed to identify relationships between serum lipids and UAE in normoalbuminuric subjects. Total HDL (p=0.02) and HDL3 cholesterol (p=0.01) levels were higher in low-normoalbuminuric subjects compared to high-normoalbuminuric subjects. In logistic regression analysis, after adjustment for age, sex, BMI, duration of diabetes and HbA1c, lower total HDL and HDL3 cholesterol levels were significantly associated with risk of higher UAE in our normoalbuminuric subjects (p≤0.01), with odds ratios of 0.34 to 0.43. Elevated total HDL and HDL3 cholesterol levels are associated with lower UAE in normoalbuminuric T1D patients. However, whether the detection of elevated total HDL and HDL3 cholesterol levels in T1D patients has protective value for development of microalbuminuria needs to be assessed in further follow-up studies.
Diaz, M; Lopez, F; Hernandez, F; Urbina, J A
L-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of L-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with L-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus L-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL + LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of L-carnitine on this parameter. The reduction of total cholesterol in VLDL + LDL particles in animals fed a cholesterol-rich diet plus L-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. L-Carnitine induced a marked decrease in the saturated to unsaturated C16 + C18 fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol
Pompili, Maurizio; Innamorati, Marco; Lester, David; Girardi, Paolo; Tatarelli, Roberto
To verify the hypothesis that suicide attempts are associated with lower serum cholesterol and triglyceride levels of patients with mood disorders, 26 patients with mood disorders (bipolar disorder and major depressive disorder) were admitted after a medically serious suicide attempt to the emergency department and then hospitalized in the psychiatric unit of the Sant' Andrea Hospital (Rome, Italy). Controls were 87 patients who had not made a recent suicide attempt. Attempters and nonattempters did not differ in the levels of serum cholesterol or triglycerides. Indeed, attempters had nonsignificantly higher serum levels of cholesterol and lower serum levels of triglycerides. The use of biologic indicators such as levels of serum cholesterol and triglycerides in the prediction of suicide risk in mood disorders was not fully supported from this small sample.
Cheung, Rebecca J; Gupta, Eric K; Ito, Matthew K
Although patients are instructed to abstain from food before having blood drawn for lipid analysis, many still drink coffee in the morning. It is unknown whether coffee consumed prior to drawing blood samples will impact fasting serum lipids. To determine whether a single 6-oz cup of coffee with or without the addition of nondairy creamer and sugar will significantly affect fasting plasma lipid profiles. This was a prospective, open-label, randomized crossover study. At the first of 2 visits, blood was drawn to measure initial fasting lipid panels, and participants were randomized to drink 6 oz of black coffee or coffee with nondairy creamer and sugar. Within 30-60 minutes of coffee consumption, blood was drawn for follow-up lipid panels. The procedure was repeated at the second visit, except the participants were crossed over to receive the alternate coffee preparation. Forty participants (26 men; age [mean +/- SD] 45 +/- 15 y) were enrolled. Total cholesterol (TC) increased from 188.2 +/- 38.1 to 191.3 +/- 39.9 mg/dL (p = 0.019) and high-density lipoprotein cholesterol (HDL-C) increased from 43.2 +/- 12.3 to 44.8 +/- 12.9 mg/dL (p < 0.001) after consumption of black coffee. Triglycerides decreased from 145.6 +/- 123.7 to 136.3 +/- 107.1 mg/dL (p = 0.014) after consumption of coffee with nondairy creamer and sugar. Changes in other lipid parameters, such as low-density lipoprotein cholesterol in either group, were not statistically significant. A single cup of coffee consumed within one hour before drawing blood resulted in statistically, but not clinically, significant differences in TC and HDL-C (black coffee) and triglycerides (coffee with creamer and sugar).
Background Metabolic dysfunctions characteristic of overt hypothyroidism (OH) start at the early stage of subclinical hypothyroidism (SCH). Na+/K+-ATPase (the sodium pump) is a transmembrane enzyme that plays a vital role in cellular activities in combination with membrane lipids. We evaluated the effects of early changes in thyroid hormone and membrane cholesterol on sodium pump activity in SCH and OH patients. Methods In 32 SCH patients, 35 OH patients, and 34 euthyroid patients, sodium pump activity and cholesterol levels in red blood cell membranes were measured. Serum thyroxine (T4) and thyroid stimulating hormone (TSH) levels were measured using enzyme-linked immunosorbent assays. Differences in their mean values were analysed using post hoc analysis of variance. We assessed the dependence of the sodium pump on other metabolites by multiple regression analysis. Results Sodium pump activity and membrane cholesterol were lower in both hypothyroid groups than in control group, OH group exhibiting lower values than SCH group. In SCH group, sodium pump activity showed a significant direct dependence on membrane cholesterol with an inverse relationship with serum TSH levels. In OH group, sodium pump activity depended directly on membrane cholesterol and serum T4 levels. No dependence on serum cholesterol was observed in either case. Conclusion Despite the presence of elevated serum cholesterol in hypothyroidism, membrane cholesterol contributed significantly to maintain sodium pump activity in the cells. A critical reduction in membrane cholesterol levels heralds compromised enzyme activity, even in the early stage of hypothyroidism, and this can be predicted by elevated TSH levels alone, without any evident clinical manifestations. PMID:28256112
Diener, A C; Li, H; Zhou, W; Whoriskey, W J; Nes, W D; Fink, G R
The side chain in plant sterols can have either a methyl or ethyl addition at carbon 24 that is absent in cholesterol. The ethyl addition is the product of two sequential methyl additions. Arabidopsis contains three genes-sterol methyltransferase 1 (SMT1), SMT2, and SMT3-homologous to yeast ERG6, which is known to encode an S-adenosylmethionine-dependent C-24 SMT that catalyzes a single methyl addition. The SMT1 polypeptide is the most similar of these Arabidopsis homologs to yeast Erg6p. Moreover, expression of Arabidopsis SMT1 in erg6 restores SMT activity to the yeast mutant. The smt1 plants have pleiotropic defects: poor growth and fertility, sensitivity of the root to calcium, and a loss of proper embryo morphogenesis. smt1 has an altered sterol content: it accumulates cholesterol and has less C-24 alkylated sterols content. Escherichia coli extracts, obtained from a strain expressing the Arabidopsis SMT1 protein, can perform both the methyl and ethyl additions to appropriate sterol substrates, although with different kinetics. The fact that smt1 null mutants still produce alkylated sterols and that SMT1 can catalyze both alkylation steps shows that there is considerable overlap in the substrate specificity of enzymes in sterol biosynthesis. The availability of the SMT1 gene and mutant should permit the manipulation of phytosterol composition, which will help elucidate the role of sterols in animal nutrition.
Diener, Andrew C.; Li, Haoxia; Zhou, Wen-xu; Whoriskey, Wendy J.; Nes, W. David; Fink, Gerald R.
The side chain in plant sterols can have either a methyl or ethyl addition at carbon 24 that is absent in cholesterol. The ethyl addition is the product of two sequential methyl additions. Arabidopsis contains three genes—sterol methyltransferase 1 (SMT1), SMT2, and SMT3—homologous to yeast ERG6, which is known to encode an S-adenosylmethionine–dependent C-24 SMT that catalyzes a single methyl addition. The SMT1 polypeptide is the most similar of these Arabidopsis homologs to yeast Erg6p. Moreover, expression of Arabidopsis SMT1 in erg6 restores SMT activity to the yeast mutant. The smt1 plants have pleiotropic defects: poor growth and fertility, sensitivity of the root to calcium, and a loss of proper embryo morphogenesis. smt1 has an altered sterol content: it accumulates cholesterol and has less C-24 alkylated sterols content. Escherichia coli extracts, obtained from a strain expressing the Arabidopsis SMT1 protein, can perform both the methyl and ethyl additions to appropriate sterol substrates, although with different kinetics. The fact that smt1 null mutants still produce alkylated sterols and that SMT1 can catalyze both alkylation steps shows that there is considerable overlap in the substrate specificity of enzymes in sterol biosynthesis. The availability of the SMT1 gene and mutant should permit the manipulation of phytosterol composition, which will help elucidate the role of sterols in animal nutrition. PMID:10852933
Tang, Qiu; Hu, Qiao-Ying; Piao, Yong-feng; Hua, Yong-Hong
Purpose To investigate the correlations between long-term survival outcomes in patients with nasopharyngeal carcinoma (NPC) and pretreatment serum low-density lipoprotein cholesterol (LDL-C) levels. Patients and methods Between January 2008 and December 2011, 935 patients with newly diagnosed NPC who were treated with intensity-modulated radiation therapy were included in this retrospective clinical analysis. Patients were divided into two groups based on pretreatment LDL-C levels: normal LDL-C (≤3.64 mmol/L; n=816) and elevated LDL-C (>3.64 mmol/L; n=119). Associations between pretreatment LDL-C levels and treatment outcome were analyzed by univariate and multivariate analyses. Results The overall patient follow-up rate was 95.1%, and 726 patients received more than 5 years of follow-up. Five-year overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) rates of the entire patient population were 87.1%, 91.1%, and 87.2%, respectively. Rates of 5-year OS, LC, and DMFS for the elevated versus normal LDL-C groups were 77.0% vs 89.1% (P<0.001), 85.8% vs 91.9% (P=0.041), and 81.1% vs 88.1% (P=0.038), respectively. Compared with normal LDL-C levels, elevated LDL-C levels were identified as an independent prognostic factor of a poorer OS (hazard ratio [HR] =2.171; 95% confidence interval [CI] =1.424–3.309), LC rate (HR =1.762; 95% CI =1.021–3.942), and DMFS (HR =1.594; 95% CI =1.003–2.532). Conclusion This study found that elevated pretreatment LDL-C levels are negative prognostic indicators of NPC. Elevated LDL-C levels may be useful indicators of locoregional control and distant metastasis in NPC patients. PMID:27217776
Nanda, Sunil Kumar; Bharathy, M; Dinakaran, Asha; Ray, Lopamudra; Ravichandran, K
Background: One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values. Aim: To evaluate the correlation of Friedewalds calculated LDL with direct LDL method. Materials and Methods: We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20–70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P < 0.05. Pearsons correlation formula was used to test the correlation between direct LDL values with Friedewald's formula. Results: There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl. Conclusion: This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method. PMID:28251110
Lissoni, P.; Brivio, F.; Pittalis, S.; Perego, M. S.; Ardizzoia, A.; Mauri, O.; Barni, S.; Crispino, S.; Tancini, G.
IL-2, in addition to its immunomodulating and antitumour properties, induces important systemic actions, including cardiovascular, neuroendocrine and metabolic effects. The present study was carried out to evaluate IL-2 effects on cholesterol metabolism. The study included 14 advanced cancer patients (renal carcinoma: ten; colon carcinoma: four), who received IL-2 subcutaneously at a dose of 1.8 x 10(6) IU ml-2 twice daily for 5 days/week for 6 weeks. Venous blood samples were collected 7 days before, on days 0, 3, 7, 14, 21, 42 of IL-2 therapy, and on days 14 and 28 of the rest-period. IL-2 induced a rapid and evident decrease in cholesterol levels, with a normalisation of its concentrations within 7 days in 10/10 hypercholesterolemic patients. The lowest mean levels of cholesterol were reached within the first 2 weeks; after that they still slowly increased. LDL-/HDL-cholesterol ratio was significantly reduced by IL-2 therapy. Cholesterol fall was associated with a marked increase in conjugated biliary acid levels. Finally, triglyceride values increased during IL-2 therapy, but not in a significant manner. These results, by showing that IL-2 exerts an evident and very rapid cholesterol-lowering activity, would represent a further demonstration of the physiological importance of cytokines in the control of cholesterol metabolism. PMID:1931624
Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J
Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.
Moreno, Leonardo; Calderas, Fausto; Sanchez-Olivares, Guadalupe; Medina-Torres, Luis; Sanchez-Solis, Antonio; Manero, Octavio
Important public health problems worldwide such as obesity, diabetes, hyperlipidemia and coronary diseases are quite common. These problems arise from numerous factors, such as hyper-caloric diets, sedentary habits and other epigenetic factors. With respect to Mexico, the population reference values of total cholesterol in plasma are around 200 mg/dL. However, a large proportion has higher levels than this reference value. In this work, we analyze the rheological properties of human blood obtained from 20 donors, as a function of cholesterol and triglyceride levels, upon a protocol previously approved by the health authorities. Samples with high and low cholesterol and triglyceride levels were selected and analyzed by simple-continuous and linear-oscillatory shear flow. Rheometric properties were measured and related to the structure and composition of human blood. In addition, rheometric data were modeled by using several constitutive equations: Bautista-Manero-Puig (BMP) and the multimodal Maxwell equations to predict the flow behavior of human blood. Finally, a comparison was made among various models, namely, the BMP, Carreau and Quemada equations for simple shear rate flow. An important relationship was found between cholesterol, triglycerides and the structure of human blood. Results show that blood with high cholesterol levels (400 mg/dL) has flow properties fully different (higher viscosity and a more pseudo-plastic behavior) than blood with lower levels of cholesterol (tendency to Newtonian behavior or viscosity plateau at low shear rates).
Türkcan, Adrian; Scharinger, Bernhard; Grabmann, Gerlinde; Keppler, Bernhard K; Laufer, Günther; Bernhard, David; Messner, Barbara
The deleterious effects of increased cadmium (Cd) serum levels on the cardiovascular system are proven by epidemiological and basic science studies. Cd exposure of animals and humans is known to impair myocardial function, possibly leading to heart failure. This study aims at investigating the effect of Cd treatment on the cardiac system with emphasis on the combined effect of Cd and high serum cholesterol levels as an important cardiovascular risk factor. Detailed analyses of Cd-induced effects on the heart of ApoE-/- mice fed a high fat diet (HFD), ApoE-/- mice fed a normal diet (ND), and C57BL/6J mice fed a ND revealed proinflammatory and fibrotic changes in the presence of cellular hypertrophy but in the absence of organ hypertrophy. Hypercholesterolemia in ApoE-/- mice alone and in combination with Cd treatment resulted in significant cardiomyocyte cell death. Based on further analyses of heart sections, we conclude that severe hypercholesterolemia in combination with ApoE-/- genotype as well as Cd treatment results in necrotic cardiomyocyte death. These data were supported by in vitro experiments showing a Cd-induced depolarization of the mitochondrial membrane and the permeabilization of the plasma membrane arguing for the occurrence of Cd-induced necrotic cell death. In summary, we were able to show for the first time that the combination of high cholesterol and Cd levels increase the risk for heart failure through cardiac fibrosis. This observation could in part be explained by the dramatically increased deposition of Cd in the hearts of ApoE-/- mice fed a HFD.
Yusuf, H K; Dickerson, J W
The content and fatty acid composition of cholesterol esters were measured in the forebrain, cerebellum, and brain stem of children who died within the first 2 years of life from severe malnutrition syndrome of kwashiorkor, marasmus, or marasmic kwashiorkor. All three brain regions of the malnourished children had elevated concentrations of cholesterol esters, compared to those of apparently normal, well-nourished children of comparable ages. This was particularly true for the brain stem, in which the elevation in some cases was 10-fold or more. In this brain region, and less pronouncedly also in the cerebellum, the elevations were more marked in the second year of life than in the first year. Fatty acid analysis showed that the developmental changes that are seen in brain cholesterol esters during normal growth, for example, fall in percentage proportions of palmitic and oleic acids and a concomitant rise in the proportion of arachidonic acid, were absent in the brain regions of the malnourished children.
Watanabe, Shinobu; Katsube, Takuya; Hattori, Hideki; Sato, Hiromasa; Ishijima, Tomoko; Nakai, Yuji; Abe, Keiko; Sonomoto, Kenji
In a previous in vitro study, we reported that the potential mechanism of the cholesterol-lowering effect of Lactobacillus brevis 119-2 isolated from turnip Tsuda kabu was the incorporation of cholesterol to cell membrane. In this study, we analyzed serum cholesterol and hepatic gene expression of Sprague-Dawley (SD) rats kept on a cholesterol diet with or without L. brevis 119-2 for 2 weeks, to evaluate the cholesterol-lowering effect in vivo. Serum cholesterol levels were significantly reduced in SD rats kept on a diet including L. brevis 119-2 compared with that in SD rats kept on a diet without L. brevis 119-2, and both viable and dead L. brevis 119-2 induced this effect. Hepatic gene analysis by DNA microarray suggested that the potential mechanism of the cholesterol-lowering effect of L. brevis 119-2 in vivo was inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase activity by insulin induced gene (Insig) protein, and induction of catabolism of cholesterol to bile acid by Cyp7a1 (cytochrome P450 a1). In addition, we found that inclusion of L. brevis 119-2 in the diet decreased serum low density lipoprotein (LDL) cholesterol levels by inducing overexpression of the LDL receptor gene. In contrast, Lactobacillus acidophilus ATCC 43121 increased high density lipoprotein cholesterol levels by inducing overexpression of the ATP-binding cassette sub-family. A member 1 (Abca1) and Angiopoietin-like 3 (Angptl3) genes. These results suggest that L. brevis 119-2 decreases the risk of atherosclerosis by lowering serum cholesterol, ameliorating the effect of fatty liver.
Wattoo, Feroza Hamid; Memon, Muhammad Saleh; Memon, Allah Nawaz; Wattoo, Muhammad Hamid Sarwar; Tirmizi, Syed Ahmed; Iqbal, Javed
To evaluate environmental, psychological and physiological stresses in college teachers and housewives, and to correlate with their serum total cholesterol, HDL cholesterol, and LDL cholesterol, and triglyceride levels. This cohort study was performed at the Institute of Biochemistry, University of Sindh, Jamshoro, Pakistan during 2003-2005. Eighty females from middle socioeconomic groups, college teachers (40) and housewives (40) aged between 25-45 years participated in this study and subjects were selected from Hyderabad and its adjoining areas. Environmental, psychological and physiological stress levels were measured with Likert scale. Total cholesterol, LDL cholesterol and HDL cholesterol were measured by CHOD-PAP method and triglyceride levels were measured by GPO method. Housewives had high levels of total cholesterol, LDL cholesterol and triglyceride but low levels of HDL cholesterol were found in college teachers. Environmental, psychological and physiological stresses were significantly higher in housewives as compared to college teachers. Housewives were under more stress than college teachers. High levels of total cholesterol, LDL cholesterol and triglyceride but low levels of HDL cholesterol were found in housewives compared to college teachers.
Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner
High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection.
Garg, Manohar L; Blake, Robert J; Wills, Ron B H
This study was conducted to assess the cholesterol-lowering potential of macadamia nuts. Seventeen hypercholesterolemic men (mean age 54 y) were given macadamia nuts (40-90 g/d), equivalent to 15% energy intake, for 4 wk. Plasma total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homocysteine concentrations and the fatty acid composition of plasma lipids were determined before and after treatment. Plasma MUFA 16:1(n-7), 18:1(n-7) and 20:1(n-9) were elevated after intervention with macadamia nuts. Plasma (n-6) and (n-3) PUFA concentrations were unaffected by macadamia nut consumption. Plasma total cholesterol and LDL cholesterol concentrations decreased by 3.0 and 5.3%, respectively, and HDL cholesterol levels increased by 7.9% in hypercholesterolemic men after macadamia nut consumption. Plasma triglyceride and homocysteine concentrations were not affected by treatment. Macadamia nut consumption was associated with a significant increase in the relative intake of MUFA and a reduced relative intake of saturated fatty acids and PUFA. This study demonstrates that macadamia nut consumption as part of a healthy diet favorably modifies the plasma lipid profile in hypercholesterolemic men despite their diet being high in fat.
Cederberg, Henna; Gylling, Helena; Miettinen, Tatu A.; Paananen, Jussi; Vangipurapu, Jagadish; Pihlajamäki, Jussi; Kuulasmaa, Teemu; Stančáková, Alena; Smith, Ulf; Kuusisto, Johanna; Laakso, Markku
We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N = 273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes. PMID:23840693
cholesterol levels. Study after study validate similar findings, that reduced cardiovascular risks are directly linked to lifestyle changes such as diet , weight...study so deduction would have it that military were not excluded. It was designed to test the hypothesis that in addition to a lipid- lowering diet ...degree of being grounded from flying until being put on medication to lower their cholesterol. The purpose of this study was to determine the prevalence of
Choudhury, Amit; Sharma, Deepak K.; Marks, David L.; Pagano, Richard E.
In normal human skin fibroblasts (HSFs), fluorescent glycosphingolipid analogues are endocytosed and sorted into two pools, one that is recycled to the plasma membrane and one that is transported to the Golgi complex. Here, we investigated glycosphingolipid recycling in Niemann-Pick type A and C lipid storage disease fibroblasts (NPFs). Cells were incubated with a fluorescent analogue of lactosylceramide (LacCer) at 16°C to label early endosomes (EEs), shifted to 37°C, and lipid recycling was quantified. Using dominant negative rabs, we showed that, in normal HSFs, LacCer recycling was rapid (t1/2 ∼8 min) and mainly rab4-dependent. In NPFs, LacCer recycling was delayed (t1/2 ∼30–40 min), and rab4-dependent recycling was absent, whereas rab11-dependent recycling predominated. Transferrin recycling via the rab4 pathway was similarly perturbed in NPFs. Compared with normal HSFs, EEs in NPFs showed high cholesterol levels and an altered organization of rab4. In vitro extraction of rab4 (but not rab11) with GDP dissociation inhibitor was severely attenuated in NPF endosomal fractions. This impairment was reversed with cholesterol depletion of isolated endosomes or with high-salt treatment of endosomes. These data suggest that abnormal membrane recycling in NPFs results from specific inhibition of rab4 function by excess cholesterol in EEs. PMID:15292453
Pena-Bello, Lara; Pértega-Diaz, Sonia; Sangiao-Alvarellos, Susana; Outeiriño-Blanco, Elena; Eiras-Leal, Raquel; Varela-Rodriguez, Bárbara; Juiz-Valiña, Paula; Pérez-Fontán, Miguel; Cordido, María; Cordido, Fernando
Context The recently identified myokine irisin conveys some of the benefits of exercise. Hypopituitarism with adult growth hormone deficiency (HP) is a situation characterized by decreased GH secretion and an altered body composition. Objective Our aim was to study the skeletal muscle hormone irisin in HP, and compare the results with a similar group of normal subjects. Participants and Methods Seventeen HP patients and fifty-one normal subjects of similar age and sex were studied. The diagnosis of GH deficiency was confirmed by the presence of pituitary disease and a peak GH secretion below 3 μg/L after an insulin tolerance test. The patients were adequately treated for all pituitary hormone deficits, except for GH. Fasting serum irisin was measured with an enzyme immunoassay, and HOMA-IR, QUICKI and HOMA-β were calculated. Results Fasting irisin levels (ng/ml) were similar in normal [208.42 (168.44–249.23)] and HP patients [195.13 (178.44–241.44)]. In the control group there were moderate significant positive correlations between irisin and BMI, waist circumference, leptin, fasting insulin, HOMA-IR, HOMA-β, triglycerides, and cholesterol. In the control group there were moderate significant negative correlations between irisin and IGF-I and QUICKI. In the hypopituitary group there were moderate significant positive correlations between irisin and body fat and HOMA-β. Conclusions We found similar irisin levels in GH deficiency hypopituitary patients when compared with normal subjects. The correlation between irisin and adiposity related factors suggests that that in the case of this clinical model, irisin is regulated by adiposity and not by GH. PMID:27472279
Yokomichi, Hiroshi; Noda, Hokuto; Nagai, Akiko; Hirata, Makoto; Tamakoshi, Akiko; Kamatani, Yoichiro; Kiyohara, Yutaka; Matsuda, Koichi; Muto, Kaori; Ninomiya, Toshiharu; Kubo, Michiaki; Nakamura, Yusuke; Yamagata, Zentaro
Controlling serum cholesterol is critical to prevent cardiovascular disease in patients with dyslipidaemia. Guidelines emphasise the need to select treatment for dyslipidaemia based on specific patient profiles; however, there is little information about the serum cholesterol levels of patients in each profile in Japan. Therefore, we aimed to describe the serum cholesterol levels and prevalence of uncontrolled cases in Japanese patients with dyslipidaemia. We included data for patients with dyslipidaemia between 2003 and 2007 from the BioBank Japan Project (66 hospitals). Then, we reported their serum cholesterol levels by age, body mass index, glycaemic control (glycated haemoglobin A1c), blood pressure, smoking, drinking, comorbidity and medication profiles. We included 22,189 male and 21,545 female patients. The mean serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and non-HDL-C levels in males were 117.4 mg/dL, 51.0 mg/dL, 187.6 mg/dL and 153.6 mg/dL, respectively; the corresponding levels in females were 129.5 mg/dL, 60.5 mg/dL, 144.9 mg/dL and 157.9 mg/dL, respectively. In both males and females, the LDL-C levels were the highest in the following profiles: age 19-44 years, body mass index 18.5-22 kg/m(2), glycated haemoglobin A1c <6.0%, never smoker, chronic respiratory disease as a comorbidity and no medication use. These data provide details of serum cholesterol levels by risk-factor profile in patients with dyslipidaemia and could add evidence of treatment decisions. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Trans fatty acid (TFA) from partially hydrogenated oil is regarded as the worst dietary fatty acid per gram due to its role in coronary heart disease. TFA consumption is decreasing worldwide, but some but not all observational studies indicate that TFA intake has little relevance to serum cholesterol levels in populations with low TFA intake (<1% E [percentage of total energy intake],
Ng, Nawi; Johnson, Owe; Lindahl, Bernt; Norberg, Margareta
Background High cholesterol is identified as a major risk factor for chronic non-communicable diseases, especially cardiovascular and cerebrovascular diseases. Monitoring trends of cholesterol levels and comparing trends across population groups are important to assess population distribution and risks related to cholesterol change over time. Cholesterol surveillance data are lacking, even in high-income countries. Objectives To describe the trends in cholesterol and triglyceride levels in different population groups and to estimate the risk of developing hypercholesterolemia and hypertriglyceridemia in Västerbotten County, Sweden during 1990–2010. Designs and Methods Since 1990, 133,082 individuals living in Västerbotten County, Northern Sweden, invited on their 30th, 40th, 50th and 60th birthdays, participated in the Västerbotten Intervention Program. Ten years after baseline data collection, 34,868 individuals were surveyed for a second time. In addition to a self-administered health questionnaire (that included information on socioeconomic status, demographics, self-reported health and lifestyle behaviours), blood cholesterol and triglyceride were examined. Results The level and prevalence of hypercholesterolemia decreased significantly from 1990 to 2007, but the trends began to increase during 2008–2010 in men, women, and in all educational groups. Men had significantly higher serum triglyceride levels than women and their cholesterol levels were similar to those of the women. This study shows that those with basic education and who live in rural inlands had consistently higher triglyceride level than those who live in the city and have higher educational attainments. People with basic education are also at higher risk of developing hypercholesterolemia and hypertriglyceridemia at 10-year follow-up; the risk is much higher among the older cohorts, particularly women. During 1990–2010, the proportion of participants who reported treatment with lipid
Ng, Nawi; Johnson, Owe; Lindahl, Bernt; Norberg, Margareta
High cholesterol is identified as a major risk factor for chronic non-communicable diseases, especially cardiovascular and cerebrovascular diseases. Monitoring trends of cholesterol levels and comparing trends across population groups are important to assess population distribution and risks related to cholesterol change over time. Cholesterol surveillance data are lacking, even in high-income countries. To describe the trends in cholesterol and triglyceride levels in different population groups and to estimate the risk of developing hypercholesterolemia and hypertriglyceridemia in Västerbotten County, Sweden during 1990-2010. Since 1990, 133,082 individuals living in Västerbotten County, Northern Sweden, invited on their 30th, 40th, 50th and 60th birthdays, participated in the Västerbotten Intervention Program. Ten years after baseline data collection, 34,868 individuals were surveyed for a second time. In addition to a self-administered health questionnaire (that included information on socioeconomic status, demographics, self-reported health and lifestyle behaviours), blood cholesterol and triglyceride were examined. The level and prevalence of hypercholesterolemia decreased significantly from 1990 to 2007, but the trends began to increase during 2008-2010 in men, women, and in all educational groups. Men had significantly higher serum triglyceride levels than women and their cholesterol levels were similar to those of the women. This study shows that those with basic education and who live in rural inlands had consistently higher triglyceride level than those who live in the city and have higher educational attainments. People with basic education are also at higher risk of developing hypercholesterolemia and hypertriglyceridemia at 10-year follow-up; the risk is much higher among the older cohorts, particularly women. During 1990-2010, the proportion of participants who reported treatment with lipid-lowering agents increased from 1.1% to 9.6% among men and
Konjufca, V H; Pesti, G M; Bakalli, R I
Male Ross x Ross 208 chickens were fed from hatching to 21 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 0, 1.5, 3.0, and 4.5% of a commercial garlic powder in Experiments 1 and 2. Once the dose-response relationship was established, 3% garlic powder or 63 or 180 mg/kg copper as cupric citrate or cupric sulfate pentahydrate were supplemented to the diet (Experiments 3, 4, 5, and 6). In the first two experiments, reductions of plasma cholesterol (P = 0.006) and triacylglycerols (P = 0.013) and liver (P = 0.012) and breast muscle (P = 0.165) cholesterol were observed in garlic-supplemented birds. Feeding either garlic powder or copper (63 and 180 mg/kg) resulted in reduced levels of plasma cholesterol, liver cholesterol, blood reduced glutathione, and breast and thigh muscle cholesterol. Differences were significant at P < 0.05 in at least one experiment. 3-Hydroxy-3-methylglutaryl reductase activity was decreased due to dietary garlic (P = 0.0369), but not by pharmacological levels of dietary copper (P = 0.982). The activity of fatty acid synthetase was decreased in birds fed copper (P = 0.035). Both garlic and copper supplements decreased cholesterol 7 alpha-hydroxylase activity (P = 0.024 and P = 0.022, respectively). The results of these trials confirm the findings that garlic and copper alter lipid and cholesterol metabolism. However, they do not work by the same mechanism. Feeding dietary garlic or copper for 21 d reduced cholesterol levels of broiler meat without altering growth of the chickens or feed efficiency.
Zafirova-Ivanovska, Beti; Stojkovikj, Jagoda; Dokikj, Dejan; Anastasova, Sasha; Debresliovska, Angela; Zejnel, Sead; Stojkovikj, Dragana
BACKGROUND: High blood cholesterol is part of metabolic syndrome and can be caused by medical conditions or bad dietary habits. AIM: The aim of the study was to investigate the prevalence of hypercholesterolemia in privies diagnosed patients with the severe and very severe stage of COPD, which were stable. MATERIAL AND METHODS: We investigated 100 subjects, all of them smokers, with smoking status >10 years, stratified into two groups: with severe and very severe stage of the disease. It was clinical, randomized, cross-sectional study. Besides demographic parameters and functional parameters, body mass index, cholesterol, LDL, and HDL were investigated. RESULTS: In the group of patients with very severe COPD were recorded significantly higher average values of cholesterol (6.16 ± 1.5 vs. 5.61 ± 1.1, p = 0.039). As independent significant factors influencing cholesterol in the group with a very severe COPD were confirmed the age of the patients (p = 0.005), LDL (p = 0.004) and HDL (p = 0.002). In the group with severe COPD, only LDL was confirmed as an independent significant factor that has an impact on cholesterol (p < 0.0001). CONCLUSION: The results of our survey demonstrated a high level of blood cholesterol and LDL, and low level of blood HDL in both investigated group’s patients with COPD. PMID:27335600
Nozue, Tsuyoshi; Yamamoto, Shingo; Tohyama, Shinichi; Fukui, Kazuki; Umezawa, Shigeo; Onishi, Yuko; Kunishima, Tomoyuki; Sato, Akira; Miyake, Shogo; Morino, Yoshihiro; Yamauchi, Takao; Muramatsu, Toshiya; Hibi, Kiyoshi; Terashima, Mitsuyasu; Suzuki, Hiroshi; Michishita, Ichiro
Aim: The efficacy of statin therapy in inducing coronary plaque regression may depend on baseline cholesterol levels. We aimed to determine the efficacy of statin therapy in inducing coronary plaque regression in statin-naïve patients with low cholesterol levels using serial intravascular ultrasound (IVUS) data from the treatment with statin on atheroma regression evaluated by virtual histology IVUS (TRUTH) study. Methods: The TRUTH study is a prospective, multicenter trial, comparing the efficacies of pitavastatin and pravastatin in coronary plaque regression in 164 patients. All patients were statin-naïve and received statin therapy only after study enrollment. The primary endpoint was the observation of coronary plaque progression, despite statin therapy. Results: Serial IVUS data, at baseline and after an 8-month follow-up, were available for 119 patients. The patients were divided into three groups based on non-high-density lipoprotein cholesterol (HDL-C) levels—low: ≤ 140 mg/dl, n = 38; moderate: 141–169 mg/dl, n = 42; and high: ≥ 170 mg/dl, n = 39. Coronary plaque progression was noted in the low cholesterol group, whereas plaque regression was noted in the moderate and high cholesterol groups [%Δplaque volume: 2.3 ± 7.4 vs. − 2.7 ± 10.7 vs. − 3.2 ± 7.5, p = 0.004 (analysis of variance)]. After adjusting for all variables, a low non-HDLC level (≤ 140 mg/dl) was identified as an independent predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence interval, 1.5–9.1, p = 0.004]. Conclusion: Serial IVUS data analysis indicated that statin therapy was less effective in inducing coronary plaque regression in patients with low cholesterol levels but more effective in those with high cholesterol levels at baseline. University Hospital Medical Information Network (UMIN) (UMIN ID: C000000311). PMID:27040362
Gato, Nobuki; Kadowaki, Akio; Hashimoto, Natsumi; Yokoyama, Shin-ichiro; Matsumoto, Kenji
Bile acid-binding agents are known to lower blood cholesterol levels and have been clinically used for the treatment of hypercholesterolemia. We previously showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had bile acid-binding properties. In this study, we performed a randomized, double-blind, placebo-controlled trial to investigate the hypocholesterolemic effects of tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12 weeks. Plasma total cholesterol levels decreased significantly in the low-dose (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001) groups. In addition, plasma low-density lipoprotein cholesterol levels decreased significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001). These improvements were not accompanied by changes in plasma high-density lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that tannin-rich fiber from young persimmon fruits is a useful food material for treating hypercholesterolemia.
Shepardson, Nina E; Shankar, Ganesh M; Selkoe, Dennis J
During the last 2 decades, evidence has accumulated that a high cholesterol level may increase the risk of developing Alzheimer disease (AD). With the global use of statins to treat hypercholesterolemia, this finding has led to the anticipation that statins could prove useful in treating or preventing AD. However, the results of work on this topic are inconsistent: some studies find beneficial effects, but other studies do not. In this first segment of a 2-part review, we examine the complex preclinical and clinical literature on cholesterol level and AD. First, we review epidemiological research on cholesterol level and the risk of AD and discuss the relevance of discrepancies among studies with regard to participants' age and clinical status. Second, we assess studies correlating cholesterol level with neuropathological AD type. The potential molecular mechanisms for the apparent adverse effects of cholesterol on the development of AD are then discussed. Third, we review preclinical studies of statin use and AD. Therefore, this first part of our review provides the background and rationale for investigating statins as potential therapeutic agents in patients with AD, the subject of the second part.
Hong, Ji Young; Yang, Go Eun; Ko, Yousang; Park, Yong Bum; Sim, Yun Su; Park, Sung Hoon; Lee, Chang Youl; Jung, Ki-Suck
Background Nutritional assessment is important in patients with pulmonary nontuberculous mycobacterial (PNTM) disease. The therapeutic effect of a cholesterol-rich diet in tuberculosis (TB) patients has been demonstrated, but the role of cholesterol in PNTM disease is unclear. This study evaluated the sequential changes in nutritional markers, including cholesterol, total lymphocyte count and visceral fat volume, according to the PNTM disease course. Methods This was an age-, sex- and number of comorbid diseases-matched case-control analysis of 89 patients with PNTM disease and 356 controls, who were participants in a Korean national survey. Results The median body mass index (BMI) and cholesterol level in the PNTM group [BMI =19.7 kg/m2; interquartile range (IQR): 17.8–21.6; cholesterol: 159 mg/dL; IQR, 135–185] were lower than those in controls (BMI: 23.1 kg/m2; IQR, 21.3–25.3; cholesterol: 188 mg/dL; IQR, 164-217; both P<0.001). In a multivariate analysis, Age more than 70 years (OR =3.38; 95% CI: 1.13–10.15, P=0.029), BMI <19.5 kg/m2 (OR =5.09; 95% CI: 1.67–15.48; P=0.004) and cavitary lesions (OR: 3.86; 95% CI: 1.30–11.47; P=0.015) were independently associated with extensive pulmonary lesions involving more than four lobes. The total cholesterol level, total lymphocyte count showed a tendency to decrease in PNTM patients with disease progression (both, P value <0.05), but not in those with a stable disease course. A decrease in cholesterol concentration of >20 mg/dL and a decrease in lymphocyte count more than 200/µL were predictive factors for disease progression (cholesterol: OR =10.50, 95% CI: 2.51–43.98, P=0.001; lymphocyte count: OR =5.32, 95% CI: 1.46–19.35, P=0.011). Conclusions These findings suggest that the change in cholesterol level may be a marker of disease progression in patients with PNTM disease. PMID:27867565
Kim, Nam-Young; Kim, Kyu-Il
We conducted two studies to determine the effect of gender, gonadectomy (GDX) on growth and plasma cholesterol levels in pigs. In experiment 1, five sham-operated and five GDX female Landrace pigs (26 kg) were allowed to have free access to water and feed up to market weight (approximately 100 kg). Body weight and feed consumption were recorded biweekly, and daily body weight gain, daily feed intake and feed efficiency (gain/feed) were calculated during the feeding period. In experiment 2, 10 male (26 kg) and 10 female (26 kg) Landrace pigs were used; five male and five female pigs were assigned to sham-operated or GDX. Pigs were allowed to have free access to water and a diet without added cholesterol (Table 1) until they were 6 months old (male 104 and female 98 kg) and thereafter they were fed a hypercholesterolemic diet (Table 1) containing 0.5% cholesterol and 0.1% cholate for 10 days. GDX of female pigs increased average daily gain (P<0.05), compared with their sham-operated counterparts during the growing-finishing period, but had no effect (P>0.05) on feed efficiency. Plasma cholesterol levels in pigs fed a hypercholesterolemic diet for 10 days were much higher (P<0.05) in females than in males (161 vs 104 mg/100 mL plasma), and were increased by GDX only in male pigs. HDL-cholesterol/LDL+VLDL-cholesterol ratio appeared to be higher in males than in females, and was not influenced by GDX in either sex. Results suggested that the lower growth rate of female pigs than their male counterparts is attributable to the ovarian activity, and the lower plasma cholesterol level in male than in female pigs fed a hypercholesterolemic diet is due to the testicular activity. PMID:20016700
Boettger, Linda M.; Salem, Rany M.; Handsaker, Robert E.; Peloso, Gina; Kathiresan, Sekar; Hirschhorn, Joel; McCarroll, Steven A.
Two exons of the human haptoglobin (HP) gene exhibit copy number variation that affects HP multimerization and underlies one of the first protein polymorphisms identified in humans. The evolutionary origins and medical significance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from the recurring reversion of an ancient hominin-specific duplication of these exons. Though this polymorphism has been largely invisible to genome-wide genetic studies to date, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We show that these deletions, and a SNP that affects HP expression, are the likely drivers of the strong but complex association of cholesterol levels to SNPs near HP. Recurring exonic deletions in the haptoglobin gene likely enhance human health by lowering cholesterol levels in the blood. PMID:26901066
Background Altered lipid profile, and in particular low HDL and high triglyceride (TG) plasma levels, are within the major determinants of cardiovascular diseases. The identification of quantitative trait loci (QTL) affecting these lipid levels is a relevant issue for predictive purposes. The WWOX gene has been recently associated with HDL levels. This gene is located at chromosome 16q23, a region previously linked to familial combined hyperlipidemia (FCHL) and HDL. Our objective is to perform a genetic association analysis at the WWOX gene region with HDL, TG and TG/HDL ratio. Methods A quantitative association analysis performed in 801 individuals selected from the Spanish general population. Results For HDL levels, two regions of intron 8 display clustering of positive signals (p < 0.05) but none of them was associated in the haplotypic analysis (0.07 ≤ p ≤ 0.165). For TG levels not only intron 8 but also a 27 kb region spanning from the promoter region to intron 4 are associated in this study. For the TG/HDL genetic association analysis, positive signals are coincident with those of the isolated traits. Interestingly, haplotypic analysis at the 5' region showed that variation in this region modified both HDL and TG levels, especially the latter (p = 0.003). Conclusions Our results suggest that WWOX is a QTL for both TG and HDL. PMID:20942981
Zaman, M. Mostafa; Choudhury, Sohel Reza; Ahmed, Jasimuddin; Talukder, Md. Habibullah; Rahman, A.H.M. Shafiqur
Background A nationally representative survey was carried out to determine the distribution of blood glucose and cholesterol in adult population of Bangladesh in the absence of existing data. Methods The study adopted a multistage and geographically clustered sampling technique of households. A total of 2610 individuals (1444 men and 1166 women) aged 25–64 years were selected from rural and urban areas. Capillary blood glucose and total cholesterol levels were measured using an overnight fasting state. Results The mean age of the participants was 41 years [standard deviation (SD), 11 years]. Half of them (49%) were from urban areas. Half of them (51%) had primary or higher education. Mean glucose was 74 mg/dL (SD 23 mg/dL). Men had higher mean glucose levels (79 mg/dL) than women (67 mg/dL). Age-standardized prevalence of diabetes (blood glucose level ≥126 mg/dL and/or use of anti-diabetic medication) was 5.5%. In men, it was almost two-and-half times (7.6%) compared with women (2.8%). It was also double in urban areas (7.8%) compared with rural areas (3.4%). Mean cholesterol level among all participants was 167 mg/dL (SD 26 mg/dL). Men and women had almost similar levels (169 mg/dL versus 166 mg/dL, respectively). Prevalence of high cholesterol level (≥240 mg/dL) was very low (1.3%) in both men (2.2%) and women (0.5%). However, the prevalence of borderline high cholesterol was substantial (5.8%) in this sample. Conclusion The prevalence of high hypercholesterolemia is low, whereas there is a high prevalence of borderline high cholesterol and diabetes in the adult population of Bangladesh. This warrants population-based interventions to tackle this problem. PMID:26896267
Zaman, M Mostafa; Choudhury, Sohel Reza; Ahmed, Jasimuddin; Talukder, Md Habibullah; Rahman, A H M Shafiqur
A nationally representative survey was carried out to determine the distribution of blood glucose and cholesterol in adult population of Bangladesh in the absence of existing data. The study adopted a multistage and geographically clustered sampling technique of households. A total of 2610 individuals (1444 men and 1166 women) aged 25-64 years were selected from rural and urban areas. Capillary blood glucose and total cholesterol levels were measured using an overnight fasting state. The mean age of the participants was 41 years [standard deviation (SD), 11 years]. Half of them (49%) were from urban areas. Half of them (51%) had primary or higher education. Mean glucose was 74mg/dL (SD 23mg/dL). Men had higher mean glucose levels (79mg/dL) than women (67mg/dL). Age-standardized prevalence of diabetes (blood glucose level ≥126mg/dL and/or use of anti-diabetic medication) was 5.5%. In men, it was almost two-and-half times (7.6%) compared with women (2.8%). It was also double in urban areas (7.8%) compared with rural areas (3.4%). Mean cholesterol level among all participants was 167mg/dL (SD 26mg/dL). Men and women had almost similar levels (169mg/dL versus 166mg/dL, respectively). Prevalence of high cholesterol level (≥240mg/dL) was very low (1.3%) in both men (2.2%) and women (0.5%). However, the prevalence of borderline high cholesterol was substantial (5.8%) in this sample. The prevalence of high hypercholesterolemia is low, whereas there is a high prevalence of borderline high cholesterol and diabetes in the adult population of Bangladesh. This warrants population-based interventions to tackle this problem. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.
Li, Josephine H.; Lao, Xiang Qian; Tillmann, Hans L.; Rowell, Jennifer; Patel, Keyur; Thompson, Alexander; Suchindran, Sunil; Muir, Andrew J.; Guyton, John R.; Gardner, Stephen D.; McHutchison, John G.; McCarthy, Jeanette J.
Background Recently, genetic polymorphisms occurring in the interferon lambda gene region were associated with response to interferon-based treatment of hepatitis C infection. Both infection with the hepatitis C virus and interferon therapy are associated with decreased serum cholesterol and high cholesterol has been associated with increased likelihood to respond to interferon. We sought to determine if the interferon lambda gene variant was also associated with serum lipid levels in chronic hepatitis C patients. We compared genotypes of the rs12979860 polymorphism, located proximal to the IL28 gene, with serum lipid and apolipoprotein levels in 746 subjects with chronic HCV infection, not currently undergoing treatment, using multivariable analysis of variance. Results Levels of total cholesterol (p=6.0×10-4), apolipoprotein B (p=1.3×10-6) and low density lipoprotein (LDL) cholesterol (p=8.9×10-10) were significantly higher in subjects carrying the rs12979860 CC ‘responder’ genotype compared to those with the CT or TT genotype. Levels of triglycerides (p=0.03), apolipoprotein A-I (p=0.06) and apolipoprotein E (p=0.01) were slightly lower in the rs12979860 CC genotype group, while levels of high density lipoprotein cholesterol (p=0.78) and apolipoprotein C-III (p=0.74) did not vary by rs12979860 genotype. Conclusions Our results suggest that low levels of LDL cholesterol in chronic hepatitis C patients may be a marker of host endogenous interferon response to hepatitis C and that subjects with the rs12979860 CC ‘responder’ genotype may have a lower endogenous interferon response to the virus. PMID:20235331
Narayan, Shreya; Lakshmipriya, Nagarajan; Vaidya, Ruchi; Bai, Mookambika Ramya; Sudha, Vasudevan; Krishnaswamy, Kamala; Unnikrishnan, Ranjit; Anjana, Ranjit Mohan; Mohan, Viswanathan
There is little data correlating dietary fibre (DF) intake and cardiovascular risk in Asian Indians with diabetes. To assess the DF intake and its association with lipid profile (total serum cholesterol and low density lipoprotein [LDL] - cholesterol levels) in urban Asian Indians with diabetes. Dietary assessment using validated Food Frequency Questionnaire was conducted in 1191 free-living adults with known diabetes in the Chennai Urban Rural Epidemiology Study. Subjects taking medication for dyslipidemia, and those with cardiovascular disease and implausible energy intake (n = 262) were excluded, leaving 929 participants. Anthropometric and relevant biochemical parameters were measured using standardized techniques. Diabetic individuals who consumed DF < median intake (29 g/day) had a higher prevalence of hypercholesterolemia (49.5% vs. 40.1% [P = 0.01]) and higher LDL cholesterol (46.2% vs. 35.5% [P = 0.001]) than those in the > median intake of DF group. The risk of hypercholesterolemia (odds ratio [OR] =1.38 [95% confidence interval [CI]: 1.02-1.85], P = 0.04), and high LDL cholesterol (OR: 1.43 [95% CI: 1.06-1.94], P = 0.02) was higher among those whose DF intake was less than the median. Serum triglycerides and high density lipoprotein cholesterol were not associated with DF intake. The main sources of DF were vegetables and legumes. In urban Asian Indians with diabetes, lower DF intake is positively related to total cholesterol and LDL cholesterol levels.
Chauhan, V.; Sheikh, A.; Chauhan, A.; Tsiouris, J.; Malik, M.; Vaughan, M.
During hibernation, fat is known to be the preferred source of energy. A detailed analysis of different phospholipids, as well as free and esterified cholesterol, was conducted to investigate lipid abnormalities during hibernation. The levels of total phospholipids and total cholesterol in the serum of black bears were found to increase significantly in hibernation as compared with the active state. Both free and esterified cholesterol were increased in the hibernating state in comparison with the active state (P < 0.05). The percentage increase during hibernation was more in free cholesterol (57%) than in esterified cholesterol (27%). Analysis of subclasses of serum phospholipids showed that choline containing phospholipids, i.e., sphingomyelin (SPG) (14%) and phosphatidylcholine (PC) (76%), are the major phospholipids in the serum of bear. The minor phospholipids included 8% of phosphatidylserine (PS) + phosphatidylinositol (PI), while phosphatidylethanolamine (PE) was only 2% of the total phospholipids. A comparison of phospholipid subclasses showed that PC, PS + PI and SPG were significantly increased, while PE was significantly decreased (P < 0.05) in the hibernating state as compared with the active state in black bears. These results suggest that the catabolism of phospholipids and cholesterol is decreased during hibernation in black bears, leading to their increased levels in the hibernating state as compared with the active state. In summary, our results indicate that serum cholesterol and phospholipid fractions (except PE) are increased during hibernation in bears. It is proposed that the increase of these lipids may be due to the altered metabolism of lipoproteins that are responsible for the clearance of the lipids. ?? 2002 E??ditions scientifiques et me??dicales Elsevier SAS and Socie??te?? franc??aise de biochimie et biologie mole??culaire. All rights reserved.
Ramírez, Cristina M.; Rotllan, Noemi; Vlassov, Alexander V.; Dávalos, Alberto; Li, Mu; Goedeke, Leigh; Aranda, Juan F.; Cirera-Salinas, Daniel; Araldi, Elisa; Salerno, Alessandro; Wanschel, Amarylis; Zavadil, Jiri; Castrillo, Antonio; Kim, Jungsu; Suárez, Yajaira; Fernández-Hernando, Carlos
Rationale Foam cell formation due to excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis, the major cause of morbidity and mortality in Western societies. Liver X nuclear receptors (LXRs) regulate the expression of the adenosine triphosphate-binding cassette (ABC) transporters, including ABCA1 and ABCG1. ABCA1 and ABCG1 facilitate the efflux of cholesterol from macrophages and regulate high-density lipoprotein (HDL) biogenesis. Increasing evidence supports the role of microRNA (miRNAs) in regulating cholesterol metabolism through ABC transporters. Objective We aimed to identify novel miRNAs that regulate cholesterol metabolism in macrophages stimulated with LXR agonists. Methods and Results To map the miRNA expression signature of macrophages stimulated with LXR agonists, we performed a miRNA profiling microarray analysis in primary mouse peritoneal macrophages stimulated with LXR ligands. We report that LXR ligands increase miR-144 expression in macrophages and mouse livers. Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to ApoA1 in macrophages. Delivery of miR-144 oligonucleotides to mice attenuates ABCA1 expression in the liver, reducing HDL levels. Conversely, silencing of miR-144 in mice increases the expression of ABCA1 and plasma HDL levels. Thus, miR-144 appears to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver. Conclusions 1) miR-144 regulates cholesterol metabolism via suppressing ABCA1 expression; and 2) modulation of miRNAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease. PMID:23519695
Leonard, Scott W; Joss, Jacqueline D; Mustacich, Debbie J; Blatt, David H; Lee, Young Sook; Traber, Maret G
The effects of vitamin E supplementation on the cholesterol levels of hypercholesterolemic patients receiving statin therapy were studied. In this prospective, single-blind, placebo-controlled, randomized trial, patients who were currently taking either lovastatin or simvastatin for a primary diagnosis of hypercholesterolemia were given placebo for two weeks and then randomized to receive a supplement of either 400 IU of vitamin E or matching placebo after dinner for eight weeks, followed by a two-week washout period. Vitamin E supplementation increased plasma alpha-tocopherol concentrations approximately 1.6-fold and increased excretion of its urinary metabolite 4-fold significantly from week 2 to week 6 (p < 0.001 for both comparisons). During the eight-week supplementation period, no statistically significant differences in any lipoprotein cholesterol fraction were detected between groups; however, a 6% decrease in high-density-lipoprotein (HDL) cholesterol was detected within the vitamin E group from week 2 to week 6 (p < 0.05), but the decrease was not sufficient to change the cardiac risk ratio. Neither cytochrome P-450 isoenzyme (CYP) 3A (as measured by hydroxylation of urinary cortisol) nor cholesteryl ester transfer protein (CETP) activity was significantly altered during the study. Vitamin E supplementation did not affect total or low-density-lipoprotein cholesterol levels in hypercholesterolemic patients receiving lovastatin or simvastatin. A small but significant decrease in HDL cholesterol levels was observed in the group that received vitamin E supplementation during the supplementation period, but this decrease was no longer significantly different from the placebo group's levels two weeks postsupplementation. The decrease in HDL cholesterol levels did not appear to be related to either CYP3A or CETP.
Zacconi, C; Bottazzi, V; Rebecchi, A; Bosi, E; Sarra, P G; Tagliaferri, L
Hypocholesterolemic effect was shown in axenic, mono, bicolonized and conventional mice: the effect was different depending on probiotic properties of intestinal microorganisms. Contamination by Enterococcus faecium CX determined the highest effect: haematic cholesterol level decrease was 16.9% in females and 7.8% in males. In mice contaminated by Lactobacillus acidophilus N5 the decrease of haematic cholesterol levels was less and not relevant in mice contaminated by conventional microflora. Enterococcus faecium CX and Lactobacillus acidophilus N5 strains were able to grow in presence of bile salts, to colonize intestinal tract, to survive at gastric conditions and to assimilate cholesterol (E. faecium more than L. acidophilus). The authors consider the possibility to associate probiotic strains with these characteristics for the health of consumers.
Williams, Paul T.; Wood, Peter D.; Vranizan, Karen M.; Albers, John J.; Garay, Susan C.; Taylor, C. Barr
Coffee intake from three-day diet records was studied in association with plasma lipoprotein concentrations in a cross-sectional sample of 77 middle-aged American men to determine the significance and form of their interrelationships. The number of cups consumed per day correlated positively with levels of apolipoprotein B (r =.27, P ≤ 0.01) and became more strongly correlated when adjusted for age, cigarette use, adiposity, aerobic capacity, nutrient intake, and stress. Coffee intake also correlated with total cholesterol and low-density lipoprotein (LDL) cholesterol levels when adjusted for these confounding factors. Graphic analyses revealed that plasma concentrations of apolipoprotein B and LDL-cholesterol were unrelated to intake of up to 2 cups of coffee per day and positively associated with intake exceeding 2 to 3 cups. These results suggest that male heavy coffee drinkers have lipoprotein profiles suggestive of increased cardiovascular disease risk, although the causality remains to be determined. PMID:3968770
Leritz, Elizabeth C; McGlinchey, Regina E; Salat, David H; Milberg, William P
We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological function. The Memory Factor was predicted by a combination of age, LDL, and triglyceride levels; both age and triglycerides were negatively associated with factor score, while LDL levels revealed a positive relationship. Both the Executive and Memory/Language factor were only explained by education, whereby more years were associated with better performance. These results provide evidence that individual cholesterol lipoproteins and triglycerides may differentially impact cognitive function, over and above other common CVD risk factors and ApoE status. Our findings demonstrate the importance of consideration of vascular risk factors, such as cholesterol, in studies of cognitive aging.
Leritz, Elizabeth C.; McGlinchey, Regina E.; Salat, David H.; Milberg, William P.
Objective We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. Method A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43–85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological function. Results The Memory Factor was predicted by a combination of age, LDL, and triglyceride levels; both age and triglycerides were negatively associated with factor score, while LDL levels revealed a positive relationship. Both the Executive and Memory/Language factor were only explained by education, whereby more years were associated with better performance. Conclusions These results provide evidence that individual cholesterol lipoproteins and triglycerides may differentially impact cognitive function, over and above other common CVD risk factors and ApoE status. Our findings demonstrate the importance of consideration of vascular risk factors, such as cholesterol, in studies of cognitive aging. PMID:26873100
Brites, Fernando Daniel; Verona, Julián; Schreier, Laura Ester; Fruchart, Jean-Charles; Castro, Graciela Rosa; Wikinski, Regina Luisa
Previous studies have shown that high density lipoprotein (HDL)-deficient states are associated with reduced paraoxonase 1 (PON1) activity. However, HDL reduction caused by primary hypertriglyceridemia has not been fully explored. The aim of the present study was to evaluate whether PON1 and platelet-activating factor acetylhydrolase (PAF-AH), two antioxidant enzymes, were altered in patients with low HDL-cholesterol levels with or without primary hypertriglyceridemia in comparison with control normolipemic subjects. We studied 24 patients with low HDL-cholesterol levels with (n=12) or without (n=12) primary hypertriglyceridemia in comparison with 12 control subjects who presented normal HDL-cholesterol and triglyceride levels. Paraoxon and phenylacetate were used as substrate for measuring PON1 activities and 1-hexadecyl-2-[3H]acetyl-glycero-3-phosphocholine for platelet-activating factor acetylhydrolase (PAF-AH) activity. Double substrate method was used to assign phenotypes. Lipid, lipoprotein, apolipoprotein, and lipoprotein particles were determined by standardized methods. Both PON1 activities were significantly reduced in patients with low HDL-cholesterol levels. This reduction could be selectively attributed to the hypertriglyceridemic subgroup. PAF-AH activity was not different between hypoalphalipoproteinemic patients and controls. PON1 activities correlated positively and significantly with HDL-cholesterol, HDL2-cholesterol, HDL3-cholesterol, HDL-phospholipids, apo A-I, apo A-II, and LpA-I:A-II. PAF-AH correlated positively and significantly with total and low density lipoprotein-cholesterol. Data from this study would suggest that in hypoalphalipoproteinemic syndrome, particularly when associated with hypertriglyceridemia, there is impairment in enzymatic antioxidant activity exclusively related with HDL.
Shores, Jaimie; Peterson, John; VanderJagt, Dorothy; Glew, Robert H.
In a recent study of boys and girls with sickle cell disease (SCD) in Nigeria, a common finding with this genetic hematologic disorder was a marked reduction in total cholesterol. Epidemiologic studies have identified a relation between low serum levels of total cholesterol (< 130 mg/dL) and increased mortality from all causes. We were interested in knowing if hypocholesterolemia was present in African-American adults with SCD. We therefore compared the plasma lipid profiles of the 16 men and 20 women with SCD who received care at the University of Texas Medical Branch at Galveston between 1996 and 2001 with those of 2,415 gender-matched African Americans who were seen at the same hospital but who did not have SCD. The age-adjusted mean total cholesterol concentrations of the SCD males and females were 147 +/- 42 mg/dL and 179 +/- 36 mg/dL, compared to male and female control values of 200 +/- 75 mg/dL and 216 +/- 61 mg/dL, respectively. These differences between SCD subjects and controls were statistically significant (p < 0.001). The LDL-cholesterol levels of the men and women with SCD (68 +/- 28 mg/dl and 95 +/- 33 mg/dl, respectively) were also significantly reduced relative to the controls (121 +/- 58 mg/dl and 128 +/- 54 mg/dl, respectively, p = 0.001). The triglyceride levels of the men with SCD were much reduced relative to the male controls (102 +/- 34 mg/dL versus 194 +/- 215 mg/dL, p = 0.02), but were not different between the SCD females and their control group. The HDL-cholesterol levels of the SCD subjects and the controls were not different. These results indicate that total cholesterol and LDL-cholesterol concentrations are significantly reduced in adult men and women with SCD in the United States, and should heighten interest in the implication that low levels of cholesterol might exacerbate the medical problems inherent in this genetic disease. PMID:14527048
Whiteside, Wendy; Tan, Meng; Yu, Sunkyung; Rocchini, Albert
To test the hypothesis that patients with complex congenital heart disease who have undergone Fontan palliation have low total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. We retrospectively reviewed the random serum lipid profiles obtained at cardiology clinic visits between May 2010 and November 2011 in patients who had undergone the Fontan procedure. We compared these serum lipid levels against age- and sex-matched established normal data from the Third National Health and Nutrition Examination Survey. Eighty-eight patients who had undergone the Fontan procedure also had laboratory test data obtained during their visits. Median total cholesterol level in the Fontan group was 127 mg/dL (IQR, 116-144 mg/dL), median HDL-C was 40 mg/dL (IQR, 33-45 mg/dL), median non-HDL-C was 86 mg/dL (IQR, 76-109 mg/dL), and median LDL-C was 66 mg/dL (IQR, 57-83 mg/dL). Total cholesterol, LDL-C, non-HDL-C, and HDL-C levels were significantly lower in patients who had undergone a Fontan procedure compared with age- and sex-matched normal individuals (mean z-score, -1.4, -1.2, -1.0, and -1.0 respectively; all P<.0001). Cholesterol levels were below the 25th percentile for age and sex for total cholesterol in 82% of patients, for LDL-C in 76%, for non-HDL-C in 67%, and for HDL-C in 57%. Patients who have undergone the Fontan procedure have significantly lower serum total cholesterol, LDL-C, HDL-C and non-HDL-C levels than age- and sex-matched normal individuals. Although the implications of this finding are unknown, it raises the possibility of abnormalities in cholesterol absorption, synthesis, or catabolism in this patient population. Copyright © 2013 Mosby, Inc. All rights reserved.
Blassberg, Robert; Macrae, James I; Briscoe, James; Jacob, John
Smith-Lemli-Opitz syndrome (SLOS) is a common autosomal-recessive disorder that results from mutations in the gene encoding the cholesterol biosynthetic enzyme 7-dehydrocholesterol reductase (DHCR7). Impaired DHCR7 function is associated with a spectrum of congenital malformations, intellectual impairment, epileptiform activity and autism spectrum disorder. Biochemically, there is a deficit in cholesterol and an accumulation of its metabolic precursor 7-dehydrocholesterol (7DHC) in developing tissues. Morphological abnormalities in SLOS resemble those seen in congenital Sonic Hedgehog (SHH)-deficient conditions, leading to the proposal that the pathogenesis of SLOS is mediated by aberrant SHH signalling. SHH signalling is transduced through the transmembrane protein Smoothened (SMO), which localizes to the primary cilium of a cell on activation and is both positively and negatively regulated by sterol molecules derived from cholesterol biosynthesis. One proposed mechanism of SLOS involves SMO dysregulation by altered sterol levels, but the salient sterol species has not been identified. Here, we clarify the relationship between disrupted cholesterol metabolism and reduced SHH signalling in SLOS by modelling the disorder in vitro. Our results indicate that a deficit in cholesterol, as opposed to an accumulation of 7DHC, impairs SMO activation and its localization to the primary cilium. © The Author 2015. Published by Oxford University Press.
Boden, William E; Probstfield, Jeffrey L; Anderson, Todd; Chaitman, Bernard R; Desvignes-Nickens, Patrice; Koprowicz, Kent; McBride, Ruth; Teo, Koon; Weintraub, William
In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk. We randomly assigned eligible patients to receive extended-release niacin, 1500 to 2000 mg per day, or matching placebo. All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). The primary end point was the first event of the composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. A total of 3414 patients were randomly assigned to receive niacin (1718) or placebo (1696). The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter (0.91 mmol per liter) to 42 mg per deciliter (1.08 mmol per liter), lowered the triglyceride level from 164 mg per deciliter (1.85 mmol per liter) to 122 mg per deciliter (1.38 mmol per liter), and lowered the LDL cholesterol level from 74 mg per deciliter (1.91 mmol per liter) to 62 mg per deciliter (1.60 mmol per liter). The primary end point occurred in 282 patients in the niacin group (16.4%) and in 274 patients in the placebo group (16.2%) (hazard ratio, 1.02; 95% confidence interval, 0.87 to 1.21; P=0.79 by the log-rank test). Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition
Husen, Saikhu Akhmad; Winarni, Dwi; Khaleyla, Firas; Kalqutny, Septian Hary; Ansori, Arif Nur Muhammad
This study aimed to explore the activity of pericarp extract of mangosteen (Garcinia mangostana L.). Mangosteen pericarp contains various active compounds which are beneficial for human health. In-vivo antioxidant assay of pericarp extract was carried out using 3-4 month male mice of strain BALB/c weighed 30-40 g. The mice were divided into two groups: normal control (KN) group and STZ-induced diabetic group. STZ induction was performed using multiple low-dose method 30 mg/kg body weight treated daily for five consecutive days. Diabetic group was separated into two subgroups: diabetic control (KD), metformin control (KM), and crude extract treatment subgroups. The fasting blood glucose and the cholesterol level were measured before and after lard treatment, we also did it on the first, seventh, and fourteenth day of mangosteen pericarp crude extract treatment. The mice were treated with mangosteen pericarp crude extract for 14 days. The MDA level of the fasting blood serum was measured. The body weight and fasting blood cholesterol level before and after lard treatment were analyzed by t-test, whereas, the fasting blood cholesterol and the MDA level were analyzed using one-way variant analysis continued with Duncan test. The correlation between the increasing body weight and the fasting blood cholesterol level was determined by Pearson correlation test. The results of the study showed that the administration of mangosteen pericarp crude extract was able to reduce the fasting blood cholesterol and the malondialdehide level significantly.
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...
The objective was to compare the effects of plant sterols (PS) consumed as a single dose (single) at breakfast or as three doses consumed with breakfast, lunch and dinner (divided) on plasma lipoprotien levels and cholesterol endogenous fractional synthesis rate (FSR). A randomized, placebo-controll...
Background/Objectives: To compare the efficacy of single versus multiple doses of plant sterols on circulating lipid level and cholesterol trafficking. Subjects/Methods: A randomized, placebo-controlled, three-phase (6 days/phase) crossover, supervised feeding trial was conducted in 19 subjects. Sub...
Hunt, C. E.; Duncan, L. A.
Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model
Kazerooni, Rashid; Watanabe, Jonathan H; Bounthavong, Mark
To investigate the association between statin adherence and changes in lipid panel outcomes from baseline in a veteran population. Retrospective cohort study using multiple linear regression models. Veterans Affairs health care system within the Veterans Integrated Service Network 22, a network of Veterans Affairs facilities in the southwest region of the United States that includes Los Angeles, San Diego, Loma Linda, and Long Beach, California, and Las Vegas, Nevada, with an enrollment of approximately 1.4 million veterans. A total of 5365 patients who were new statin users between December 1, 2006, and November 30, 2007; 2674 patients were in the adherent group and 2691 were in the nonadherent group. Adherence was determined by the medication possession ratio. Patients were categorized as adherent if the medication possession ratio at follow-up was 0.80 or more. Adherent patients exhibited significant differences in baseline demographic and clinical characteristics than nonadherent patients in our study sample. Baseline laboratory values for adherent patients were significantly lower for low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), non-high-density lipoprotein cholesterol (non-HDL), and total cholesterol levels. The primary outcome was change in LDL level from baseline at 12 months. Secondary outcomes were changes in non-HDL and total cholesterol levels from baseline at 12 months. Independent variables controlled for in the multiple linear regression included age, sex, body mass index, race-ethnicity, baseline lipid panel (LDL, HDL, total cholesterol, and triglycerides), statin copayment status, income quintile (according to ZIP code median household income), baseline medication count, statin prescribed, and comorbidities. Multiple linear regression revealed that adherent patients demonstrated significantly greater reductions in LDL of 20.98 mg/dl versus nonadherent patients (p<0.0001). Adherent patients similarly
Leite, Jose Oyama; Fernandez, Maria Luz
The inverse correlation between high-density lipoprotein (HDL) levels and cardiovascular disease has driven several investigators to target the increase in this lipoprotein to prevent atherosclerosis and its complications. However, many reports have demonstrated that the use of HDL cholesterol (HDL-C) levels as a means to prevent and treat atherosclerosis has mainly resulted in negative outcomes. These findings may help to increase our knowledge of HDL metabolism and its protective effect. There is evidence that the mechanism by which HDL-C levels are raised has a great impact on cardiovascular outcomes. When the increase in HDL-C levels is secondary to greater synthesis, a strong beneficial effect in the prevention of cardiovascular diseases is observed. Even small increases in HDL-C levels induce a marked reduction in cardiovascular events; this has been observed during treatment with fibrates. In contrast, when the increase in HDL-C levels is secondary to a reduction in HDL catabolism, unexpectedly, the opposite effects are usually noted. Even dramatic increases in HDL-C levels are not associated with better cardiovascular outcomes. In fact, these increases have been related to a greater number of cardiovascular-related deaths. This became clear from the results of trials that tested inhibitors of cholesteryl ester transfer protein (CETP). We suggest that increases in reverse cholesterol transport are more important than HDL-C levels. Strong evidence is provided by individuals that express apolipoprotein (apo)A-I Milano. These individuals have extremely low HDL-C levels due to greater catabolism of the lipoprotein. However, reverse cholesterol transport is increased in these individuals and, as a consequence, they have a low incidence of cardiovascular diseases. We reinforce that, in clinical practice, the currently recommended levels of HDL-C should still be a major target to be aimed for. However, in the research field, we emphasize the need to look for other
Devaraj, Sridevi; Jialal, Ishwarlal; Vega-López, Sonia
Hypercholesterolemia is a major risk factor for coronary artery disease. Therapeutic lifestyle changes include dietary modifications such as inclusion of phytosterols, which effectively lowers low-density lipoprotein (LDL) cholesterol in margarines and other fats. Their effectiveness in nonfat moieties is not yet established. The aim of this study was to examine if phytosterols alter the plasma lipoprotein profile when incorporated into nonfat orange juice. After a 2-week run-in phase with orange juice, 72 mildly hypercholesterolemic healthy subjects were randomized to receive either placebo orange juice (placebo OJ) or plant sterol-fortified orange juice (sterol OJ) (2g/d) for 8 weeks. Fasting blood was obtained at baseline, after 2 weeks of OJ, and after 8 weeks of placebo/sterol-OJ supplementation. Sterol OJ supplementation significantly decreased total (7.2%), LDL (12.4%), and non-high-density lipoprotein (HDL) cholesterol (7.8%) compared with baseline and compared with placebo OJ (P<0.01). Apolipoprotein B levels were significantly decreased (9.5%) with sterol OJ. There were no significant changes in HDL cholesterol or triglycerides with the sterol OJ. While folate and B12 levels significantly increased, homocysteine levels were unchanged. Orange juice fortified with plant sterols are effective in reducing LDL cholesterol and could easily be incorporated into the therapeutic lifestyle changes dietary regimen.
Wilson, T A; DeSimone, A P; Romano, C A; Nicolosi, R J
The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol
Cai, Anping; Li, Xida; Zhong, Qi; Li, Minming; Wang, Rui; Liang, Yingcong; Chen, Wenzhong; Huang, Tehui; Li, Xiaohong; Zhou, Yingling; Li, Liwen
The aim of the present study was to evaluate the association between HDL cholesterol level and all-cause mortality in patients with ejection fraction reduced heart failure (EFrHF) complicating coronary heart disease (CHD).A total of 323 patients were retrospectively recruited. Patients were divided into low and high HDL cholesterol groups. Between-group differences and associations between HDL cholesterol level and all-cause mortality were assessed.Patients in the high HDL cholesterol group had higher HDL cholesterol level and other lipid components (P <0.05 for all comparison). Lower levels of alanine aminotransferase (ALT), high-sensitivity C-reactive protein (Hs-CRP), and higher albumin (ALB) level were observed in the high HDL cholesterol group (P <0.05 for all comparison). Although left ventricular ejection fraction (LVEF) were comparable (28.8 ± 4.5% vs 28.4 ± 4.6%, P = 0.358), mean mortality rate in the high HDL cholesterol group was significantly lower (43.5% vs 59.1%, P = 0.007). HDL cholesterol level was positively correlated with ALB level, while inversely correlated with ALT, Hs-CRP, and NYHA classification. Logistic regression analysis revealed that after extensively adjusted for confounding variates, HDL cholesterol level remained significantly associated with all-cause mortality although the magnitude of association was gradually attenuated with odds ratio of 0.007 (95% confidence interval 0.001-0.327, P = 0.012).Higher HDL cholesterol level is associated with better survival in patients with EFrHF complicating CHD, and future studies are necessary to demonstrate whether increasing HDL cholesterol level will confer survival benefit in these populations of patients.
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De Graaf, Jacqueline; De Sauvage Nolting, Pernette R W; Van Dam, Marjel; Belsey, Elizabeth M; Kastelein, John J P; Haydn Pritchard, P; Stalenhoef, Anton F H
In a randomized, double-blind, placebo-controlled trial we evaluated the effect of dietary chocolates enriched with a wood-based phytosterol-phytostanol mixture, containing 18 % (w/w) sitostanol, compared with placebo dietary chocolates in seventy subjects with primary hypercholesterolaemia (total cholesterol levels below 8 mmol/l). For 4 weeks, participants consumed three servings of the phytosterol-enriched chocolate/d that provided 1.8 g unesterified phytosterols/d or a placebo chocolate in conjunction with a low-fat, low-cholesterol diet. Plasma total and LDL-cholesterol levels were statistically significantly reduced by 6.4 % (-0.44 mmol/l) and 10.3 % (-0.49 mmol/l), respectively, after 4 weeks of phytosterol-enriched-chocolate treatment. Plasma HDL-cholesterol and triacylglycerol levels were not affected. Consumption of phytosterol-enriched chocolates significantly increased plasma lathosterol concentration (+20.7 %), reflecting an increased endogenous cholesterol synthesis in response to phytosterol-induced decreased intestinal cholesterol absorption. Furthermore, the chocolates enriched with phytosterols significantly increased both plasma sitosterol (+95.8 %) and campesterol (+64.1 %) levels, compared with the placebo chocolate group. However, the absolute values of plasma sitosterol and campesterol remained within the normal range, that is, below 10 mg/l. The chocolates with phytosterols were palatable and induced no clinical or biochemical side effects. These findings indicate that dietary chocolate enriched with tall oil-derived phytosterols (1.8 g/d) is effective in lowering blood total and LDL-cholesterol levels in subjects with mild hypercholesterolaemia and thus may be helpful in reducing the risk of CHD in these individuals.
Vacchiano, G; Maldonado, A Luna; Ros, M Matas; Di Lorenzo, P; Pieri, M
Cholesterol levels in the median nerve were studied at various post-mortem intervals (PMIs). Single median nerve samples were collected from the wrists of 36 subjects during forensic autopsies of subjects with known circumstances and times of death. Although the absolute values varied, increments in cholesterol concentration were recorded. Subsequently, 16 subjects who did not suffer of any neurological and/or metabolic diseases with known times and circumstances of death were enrolled. For each enrolled subject, two samples were collected from the wrist at an interval of approximately two hours (t1 and t2). The obtained results revealed a gradual increase in cholesterol level with increasing time since death. The cholesterol concentration data obtained for each subject at t1 and t2 were correlated with the time since death, a linear interpolation was applied, and the PMI was back-calculated. Similar trends were obtained for the samples collected at similar PMIs; thus, three groups were considered: PMI<48h, 48
Trumbo, Paula R; Shimakawa, Tomoko
Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. © 2011 International Life Sciences Institute.
Wang, Y W; Jones, P J H; Pischel, I; Fairow, C
The current study was carried out to examine the effects of policosanols and phytosterols, alone and in combination, on lipid profiles, cholesterol biosynthesis, and tissue histopathological changes in hamsters. Fifty male Golden Syrian hamsters, weighing 100 to 120 g, were fed a regular rodent chow for 2 wk before being randomly assigned into 5 groups of 10 animals each fed semisynthetic diets for 4 wk. Group 1 was given a control diet that contained 0.25% cholesterol and 5% fat with a PUFA to saturated FA ratio of 0.4. Groups 2 to 5 were fed the control diet and given Octa-6 [a policosanol mixture from sugar cane wax, 25 mg/kg body weight (BW)], Ricewax (a policosanol mixture from rice wax with 50% being converted to the corresponding acids, 50 mg/kg BW), phytosterols (Cholestatin; 1,000 mg/kg BW), and Ricewax (50 mg/kg BW) plus phytosterols (1,000 mg/kg BW), respectively. The results showed that there was no difference between Octa-6 and Ricewax treatments in any of the lipid parameters measured, and both had similar levels of triglyceride (TG), total cholesterol (T-C), and HDL cholesterol (HDL-C) as the control. Octa-6 but not Ricewax increased (P = 0.03) non-HDL-C as compared with the control. Phytosterols reduced T-C (P < 0.0003) and HDL-C (P < 0.004) without a significant effect on TG and non-HDL-C as compared to the control. Ricewax plus phytosterols had effects similar to those with phytosterols alone. Free cholesterol synthetic rates were not different among the treatments. Policosanols or phytosterols did not show any toxic effects in liver, heart, brain, or kidney. Results suggest that, although phytosterols reduce T-C and HDL-C levels, policosanols have no significant favorable effect in changing lipid levels in hamsters.
Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.
Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-cholesterol diet. The cholesterol accumulation phenotype can be attributed to misregulation of npc1b, an ortholog of the mammalian Niemann-Pick C1-like 1 gene NPC1L1, which is essential for dietary cholesterol uptake. These studies define DHR96 as a central regulator of cholesterol homeostasis. PMID:19952106
Horner, Michael A; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M; Thummel, Carl S
Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-cholesterol diet. The cholesterol accumulation phenotype can be attributed to misregulation of npc1b, an ortholog of the mammalian Niemann-Pick C1-like 1 gene NPC1L1, which is essential for dietary cholesterol uptake. These studies define DHR96 as a central regulator of cholesterol homeostasis.
Jones, P J; Howell, T; MacDougall, D E; Feng, J Y; Parsons, W
To assess the short-term cholesterol-lowering potential of sitostanol-containing tall oil plant sterols, 22 subjects consumed fixed-food diets over two 10-day periods with or without 21.2 mg/kg body weight/d tall oil phytosterols (sitosterol 62%, sitostanol 21%, campesterol 16%, and campestanol 1%) in a randomized crossover study design. On day 10 of each diet, plasma lipoprotein cholesterol levels, plasma phytosterol concentrations, and cholesterol biosynthesis rates were determined. Total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels were lower (P < .01) after administration of tall oil phytosterol (4.7 +/- 0.3 and 3.0 +/- 0.3 mmol/L, respectively) versus placebo (5.0 +/- 0.3 and 3.2 +/- 0.3 mmol/L, respectively). Tall oil treatment had no effect on the plasma high-density lipoprotein (HDL) cholesterol level (1.1 +/- 0.1 mmol/L) versus placebo (1.1 +/- 0.1 mmol/L). Similarly, plasma triglyceride (TG) levels did not differ between tall oil (1.3 +/- 0.2 mmol/L) and placebo (1.4 +/- 0.2 mmol/L) treatments. Plasma campesterol (15.8 +/- 3.7 mmol/mol cholesterol) and sitosterol (6.0 +/- 2.1 mmol/mol cholesterol) levels were not different after tall oil treatment versus placebo treatment (15.4 +/- 2.3 and 6.4 +/- 2.0 mmol/mol cholesterol, respectively). Plasma sitostanol levels were essentially undetectable. No difference was observed in cholesterol biosynthesis between tall oil (0.045 +/- 0.004 pools/d) and placebo (0.034 +/- 0.004 pools/d) treatments; however, the effect of treatments in subjects with different cholesterol levels varied. In subjects with lower cholesterol values, the red blood cell cholesterol fractional synthesis rate (FSR) increased from 0.0291 +/- 0.0054 pools/d after placebo to 0.0509 +/- 0.0049 pools/d (P < .05) after phytosterol treatment. In subjects with higher cholesterol values, the red blood cell cholesterol FSR did not change significantly after treatment. These results demonstrate the short-term efficacy of tall
Alavaikko, M.; Elfving, Riitta; Hirvonen, J.; Järvi, J.
The triglyceride, cholesterol, and phospholipid contents of heart papillary muscle were measured in groups of obviously healthy and diseased females and males on whom either routine or forensic necropsies were performed. In healthy men the triglyceride content was 1·77 ± 1·30 mg/g of wet weight and in women 1·25 ± 0·48 mg/g wet weight. The corresponding values for cholesterol were 1·07 ± 0·24 mg/g and 1·21 ± 0·22 mg/g and those for phospholipids 17·70 ± 5·15 mg/g and 19·65 ± 10·21 mg/g. The differences between the sexes were not significant. The hypertensive or cardiac hypertrophy group had about the same or slightly lower means for lipid content. In the cholelithiasis group, women had significantly high triglyceride values (3·38 ± 2·36 mg/g). The cholesterol values were not significantly elevated in either men or women. In the diabetic group, triglycerides were significantly increased both in men (mean 8·12 ± 0·54 mg/g) and in women (6·85 ± 5·66 mg/g). The cholesterol mean values were also high in both sexes, but the rise was not significant because of the great variation. In the coronary atheroma group, both male and female hospital cases had high triglyceride contents (mean 4·48 ± 4·25 mg/g and 3·65 ± 3·94 mg/g) whereas the forensic cases had only slightly elevated or normal values. Cholesterol assays paralleled the triglyceride ones, but phospholipids showed an inverse trend. The results showed that the lipid content of papillary muscle was increased in diseases where disturbances of lipid metabolism are evident, as in diabetes and cholelithiasis. In coronary atheroma only those cases with advanced obstruction of the arteries were associated with abnormal values of papillary lipids. No increase of the lipid content with age alone was found, nor was there any correlation with obesity. PMID:4267165
Simoons, M L; Casparie, A F
For the second time the consensus text for lipid lowering therapy is revised. In angiographic studies it was shown that a decrease in the total cholesterol as well as the low-density lipoprotein cholesterol level results in a reduction of the progression of vascular disease. Furthermore, intervention trials demonstrated that therapy with cholesterol synthesis inhibitors reduces not only both the cardiovascular and total mortality, but also other manifestations of coronary heart disease (CHD). Hypercholesterolaemia is treated with a low-fat diet and normalisation of the weight. For individuals, this might result in a reduction of the risk for myocardial infarction or death and for the population in a decrease of the mean serum cholesterol concentration and the incidence of CHD. The indication for drug therapy is founded on the expected effectiveness to reduce the incidence of (new manifestations of) CHD, which is related to the level of the absolute risk of vascular disease. In persons without known vascular diseases this risk is calculated from the total and high-density lipoprotein cholesterol ratio, age, sex, blood pressure, diabetes mellitus, and smoking. Treatment with cholesterol synthesis inhibitors must be considered in (a) patients with familial hypercholesterolaemia, (b) all patients with a history of myocardial infarction or other symptomatic vascular disease with a total cholesterol concentration above 5.0 mmol/l and a life expectancy of at least five years; (c) persons with a combination of diabetes mellitus, hypertension, hypercholesterolaemia and high risk for development of CHD, rising from 25% per 10 years at the age of 40 years to 35-40% per 10 years at the age of 70 years, with a life expectancy of at least five years. If these guidelines are followed, the upper limit of the calculated cost-effectiveness is about Dfl. 40,000 per life year gained. The working group judges this reasonable in comparison with other therapeutic interventions in the
Narayan, Shreya; Lakshmipriya, Nagarajan; Vaidya, Ruchi; Bai, Mookambika Ramya; Sudha, Vasudevan; Krishnaswamy, Kamala; Unnikrishnan, Ranjit; Anjana, Ranjit Mohan; Mohan, Viswanathan
Context: There is little data correlating dietary fibre (DF) intake and cardiovascular risk in Asian Indians with diabetes. Aim: To assess the DF intake and its association with lipid profile (total serum cholesterol and low density lipoprotein [LDL] - cholesterol levels) in urban Asian Indians with diabetes. Subjects and Methods: Dietary assessment using validated Food Frequency Questionnaire was conducted in 1191 free-living adults with known diabetes in the Chennai Urban Rural Epidemiology Study. Subjects taking medication for dyslipidemia, and those with cardiovascular disease and implausible energy intake (n = 262) were excluded, leaving 929 participants. Anthropometric and relevant biochemical parameters were measured using standardized techniques. Results: Diabetic individuals who consumed DF < median intake (29 g/day) had a higher prevalence of hypercholesterolemia (49.5% vs. 40.1% [P = 0.01]) and higher LDL cholesterol (46.2% vs. 35.5% [P = 0.001]) than those in the > median intake of DF group. The risk of hypercholesterolemia (odds ratio [OR] =1.38 [95% confidence interval [CI]: 1.02–1.85], P = 0.04), and high LDL cholesterol (OR: 1.43 [95% CI: 1.06–1.94], P = 0.02) was higher among those whose DF intake was less than the median. Serum triglycerides and high density lipoprotein cholesterol were not associated with DF intake. The main sources of DF were vegetables and legumes. Conclusion: In urban Asian Indians with diabetes, lower DF intake is positively related to total cholesterol and LDL cholesterol levels. PMID:25285277
Mathews, C. Bobby; Libish, T. M.; Kaushalkumar, B.; Vivek, V.; Prabhu, Radhakrishna; Radhakrishnan, P.
A fiber optic sensor for the measurement of total cholesterol is designed and developed. The developed chitosan coated long period grating (LPG) sensor shows a sensitivity of 5.025×106 pm·mL/g in the measurement range of the sensor. The sensor also shows a linear response in the measured range of cholesterol levels, which is highly desirable for exploitation as a commercial cholesterol sensor.
Molugu, Trivikram R.
Applications of solid-state NMR spectroscopy for investigating the influences of lipid-cholesterol interactions on membrane fluctuations are reviewed in this paper. Emphasis is placed on understanding the energy landscapes and fluctuations at an emergent atomistic level. Solid-state 2H NMR spectroscopy directly measures residual quadrupolar couplings (RQCs) due to individual C–2H labeled segments of the lipid molecules. Moreover, residual dipolar couplings (RDCs) of 13C–1H bonds are obtained in separated local-field NMR spectroscopy. The distributions of RQC or RDC values give nearly complete profiles of the order parameters as a function of acyl segment position. Measured equilibrium properties of glycerophospholipids and sphingolipids including their binary and tertiary mixtures with cholesterol show unequal mixing associated with liquid-ordered domains. The entropic loss upon addition of cholesterol to sphingolipids is less than for glycerophospholipids and may drive the formation of lipid rafts. In addition relaxation time measurements enable one to study the molecular dynamics over a wide time-scale range. For 2H NMR the experimental spin-lattice (R1Z) relaxation rates follow a theoretical square-law dependence on segmental order parameters (SCD) due to collective slow dynamics over mesoscopic length scales. The functional dependence for the liquid-crystalline lipid membranes is indicative of viscoelastic properties as they emerge from atomistic-level interactions. A striking decrease in square-law slope upon addition of cholesterol denotes stiffening relative to the pure lipid bilayers that is diminished in the case of lanosterol. Measured equilibrium properties and relaxation rates infer opposite influences of cholesterol and detergents on collective dynamics and elasticity at an atomistic scale that potentially affects lipid raft formation in cellular membranes. PMID:27154600
Molugu, Trivikram R; Brown, Michael F
Applications of solid-state NMR spectroscopy for investigating the influences of lipid-cholesterol interactions on membrane fluctuations are reviewed in this paper. Emphasis is placed on understanding the energy landscapes and fluctuations at an emergent atomistic level. Solid-state (2)H NMR spectroscopy directly measures residual quadrupolar couplings (RQCs) due to individual C-(2)H labeled segments of the lipid molecules. Moreover, residual dipolar couplings (RDCs) of (13)C-(1)H bonds are obtained in separated local-field NMR spectroscopy. The distributions of RQC or RDC values give nearly complete profiles of the order parameters as a function of acyl segment position. Measured equilibrium properties of glycerophospholipids and sphingolipids including their binary and tertiary mixtures with cholesterol show unequal mixing associated with liquid-ordered domains. The entropic loss upon addition of cholesterol to sphingolipids is less than for glycerophospholipids and may drive the formation of lipid rafts. In addition relaxation time measurements enable one to study the molecular dynamics over a wide time-scale range. For (2)H NMR the experimental spin-lattice (R1Z) relaxation rates follow a theoretical square-law dependence on segmental order parameters (SCD) due to collective slow dynamics over mesoscopic length scales. The functional dependence for the liquid-crystalline lipid membranes is indicative of viscoelastic properties as they emerge from atomistic-level interactions. A striking decrease in square-law slope upon addition of cholesterol denotes stiffening relative to the pure lipid bilayers that is diminished in the case of lanosterol. Measured equilibrium properties and relaxation rates infer opposite influences of cholesterol and detergents on collective dynamics and elasticity at an atomistic scale that potentially affects lipid raft formation in cellular membranes.
Machado, Ana Cristina Posch; Quirino, Maria Rozeli de Souza; Nascimento, Luiz Fernando Costa
Many people in the world are affected by hyperlipidemia, which is a known risk factor for atherosclerotic disease. On the other hand, periodontitis, a prevalent oral disease, has been connected to several systemic health changes, including an altered lipid metabolism. Transient and recurrent bacteremias, which may be caused by periodontal infection, induce an intense local and systemic inflammatory response, leading to changes in the whole body. The aim of the present study was to verify the relationship between severe and moderate periodontal disease and blood lipid levels. Sixty individuals seen at the clinics of the University of Taubaté, São Paulo, over 20 years old, were divided into two groups, with and without periodontitis, and paired according to sex and age. Their levels of total cholesterol, tryglicerides and fractions were determined. Variables related to high cholesterol levels, including age, sex and body mass index, were evaluated. The values recommended by the Brazilian Society of Cardiology were considered to classify lipidemia. The results showed that mean levels of cholesterol (192.1 mg/dl +/- 40.9) and triglycerides (153.5 mg/dl +/- 105.6) in individuals with periodontitis were higher than, but not statistically different from, those of individuals without periodontitis (186.1 mg/dl +/- 35.4 and 117.5 mg/dl +/- 68, respectively). Therefore, this study has demonstrated that there is no significant relationship between periodontal disease, regardless of its intensity, and blood lipid levels in the studied population.
Kohli, Rakhi; Winston, Diana; Sheehan, Heidi; Muzzio, Estela; Benetucci, Jorge; Weissenbacher, Mercedes; Wanke, Christine; Knox, Tamsin; Tang, Alice
Improved understanding of cholesterol levels in HIV and HCV-infected persons in Argentina will guide optimal antiretroviral therapy. We conducted a cross-sectional study in Argentina to describe associations between HIV, Hepatitis C and cholesterol. Of 202 participants, 21 were HIV-infected, 15 HCV-infected, 46 were HIV/HCV co-infected and 120 were HIV/HCV uninfected. HIV/HCV uninfected participants had the highest total cholesterol (TC) and LDL levels. Multivariate modeling revealed that HIV/HCV co-infected patients had the lowest TC levels (−28.7 mg/dl, p<0.001) compared to the HIV/HCV uninfected reference group. HCV and HIV/HCV co-infection were associated with lower LDL levels (−21.4 mg/dL, p=0.001 and −20.3 mg/dL, p<0.0001, respectively). HIV and HIV/HCV co-infection, but not HCV alone, were associated with lower HDL levels (−9.1 mg/dL, p=0.0008 and −6.8 mg/dl, p=0.0006 respectively). Further study is needed to examine if the more favorable lipid profile observed in HIV/HCV co-infected persons is associated with a reduction in cardiovascular risk. PMID:26518591
Kohli, Rakhi; Winston, Diana; Sheehan, Heidi; Muzzio, Estela; Benetucci, Jorge; Weissenbacher, Mercedes; Wanke, Christine; Knox, Tamsin; Tang, Alice
Improved understanding of cholesterol levels in HIV- and hepatitis C virus (HCV)-infected persons in Argentina will guide optimal antiretroviral therapy. The authors conducted a cross-sectional study in Argentina to describe associations between HIV, HCV, and cholesterol. Of the 202 participants, 21 were HIV infected, 15 were HCV infected, 46 were HIV/HCV coinfected, and 120 were HIV/HCV uninfected. HIV/HCV-uninfected participants had the highest total cholesterol (TC) and low-density lipoprotein (LDL) levels. Multivariate modeling revealed that HIV/HCV-coinfected patients had the lowest TC levels (-28.7 mg/dL, P < .001) compared to the HIV/HCV-uninfected reference group. Hepatitis C virus and HIV/HCV coinfection were associated with lower LDL levels (-21.4 mg/dL, P = .001 and -20.3 mg/dL, P < .0001, respectively). HIV and HIV/HCV coinfection, but not HCV alone, were associated with lower high-density lipoprotein levels (-9.1 mg/dL, P = .0008 and -6.8 mg/dL, P = .0006, respectively). Further study is needed to examine whether the more favorable lipid profile observed in HIV/HCV-coinfected persons is associated with a reduction in cardiovascular risk. © The Author(s) 2015.
Qualls, Laura G; Hammill, Bradley G; Maciejewski, Matthew L; Curtis, Lesley H; Jones, W Schuyler
At the time of this study, guidelines recommended a primary goal of low-density lipoprotein cholesterol level less than 100 mg/dL for all patients, an optional goal of low-density lipoprotein cholesterol less than 70 mg/dL for patients with overt cardiovascular disease and statins for patients with diabetes and overt cardiovascular disease and patients 40 years and older with diabetes and at least one risk factor for cardiovascular disease. This study examined statin use and achievement of lipid goals among 111,730 Medicare fee-for-service beneficiaries 65 years and older in 2011. Three-quarters of patients met the low-density lipoprotein cholesterol goal of less than 100 mg/dL. Patients with cardiovascular disease were more likely to meet the goal than those without, not controlling for other differences. Patients on a statin were more likely to meet the goal. There is considerable opportunity for improvement in cholesterol management in high-risk patients with diabetes mellitus. © The Author(s) 2016.
Smith, G D; Song, F; Sheldon, T A
OBJECTIVE--To investigate the level of risk of death from coronary heart disease above which cholesterol lowering treatment produces net benefits. DESIGN--Meta-analysis of results of randomised controlled trials of cholesterol lowering treatments. METHODS--Published and unpublished data from all identified randomised controlled trials of cholesterol lowering treatments with six months or more follow up and with at least one death were included in the meta-analysis. The analyses were stratified by the rate of death from coronary heart disease in the control arms of the trials. MAIN OUTCOME MEASURES--Death from all causes, from coronary heart disease, and from causes other than coronary heart disease. RESULTS--In the pooled analysis, net benefit in terms of total mortality from cholesterol lowering was seen only for trials including patients at very high initial risk of coronary heart disease (odds ratio 0.74; 95% confidence interval 0.60 to 0.92). In a medium risk group no net effect was seen, and in the low risk group there were adverse treatment effects (1.22; 1.06 to 1.42). In a weighted regression analysis a significant (p < 0.001) trend of increasing benefit with increasing initial risk of coronary heart disease was shown. Raised mortality from causes other than coronary heart disease was seen in trials of drug treatment (1.21; 1.05 to 1.39) but not in the trials of non-drug treatments (1.02; 0.88 to 1.19). Cumulative meta-analysis showed that these results seem to have been stable as new trials appeared. CONCLUSION--Currently evaluated cholesterol lowering drugs seem to produce mortality benefits in only a small proportion of patients at very high risk of death from coronary heart disease. Population cholesterol screening could waste resources and even result in net harm in substantial groups of patients. Overall risk of coronary heart disease should be the main focus of clinical guidelines, and a cautious approach to the use of cholesterol lowering drugs
Eskelinen, Eeva-Liisa; Schmidt, Christine Katrin; Neu, Silja; Willenborg, Marion; Fuertes, Graciela; Salvador, Natalia; Tanaka, Yoshitaka; Lüllmann-Rauch, Renate; Hartmann, Dieter; Heeren, Jörg; von Figura, Kurt; Knecht, Erwin; Saftig, Paul
Mice double deficient in LAMP-1 and -2 were generated. The embryos died between embryonic days 14.5 and 16.5. An accumulation of autophagic vacuoles was detected in many tissues including endothelial cells and Schwann cells. Fibroblast cell lines derived from the double-deficient embryos accumulated autophagic vacuoles and the autophagy protein LC3II after amino acid starvation. Lysosomal vesicles were larger and more peripherally distributed and showed a lower specific density in Percoll gradients in double deficient when compared with control cells. Lysosomal enzyme activities, cathepsin D processing and mannose-6-phosphate receptor expression levels were not affected by the deficiency of both LAMPs. Surprisingly, LAMP-1 and -2 deficiencies did not affect long-lived protein degradation rates, including proteolysis due to chaperone-mediated autophagy. The LAMP-1/2 double-deficient cells and, to a lesser extent, LAMP-2 single-deficient cells showed an accumulation of unesterified cholesterol in endo/lysosomal, rab7, and NPC1 positive compartments as well as reduced amounts of lipid droplets. The cholesterol accumulation in LAMP-1/2 double-deficient cells could be rescued by overexpression of murine LAMP-2a, but not by LAMP-1, highlighting the more prominent role of LAMP-2. Taken together these findings indicate partially overlapping functions for LAMP-1 and -2 in lysosome biogenesis, autophagy, and cholesterol homeostasis. PMID:15121881
Lu, Wensheng; Cheng, Yu-Ching; Chen, Keping; Wang, Hong; Gerhard, Glenn S; Still, Christopher D; Chu, Xin; Yang, Rongze; Parihar, Ankita; O'Connell, Jeffrey R; Pollin, Toni I; Angles-Cano, Eduardo; Quon, Michael J; Mitchell, Braxton D; Shuldiner, Alan R; Fu, Mao
Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related events that is under strong genetic control (heritability = 0.68-0.98). However, causal mutations and functional validation of biological pathways modulating Lp(a) metabolism are lacking. We performed a genome-wide association scan to identify genetic variants associated with Lp(a)-cholesterol levels in the Old Order Amish. We confirmed a previously known locus on chromosome 6q25-26 and found Lp(a) levels also to be significantly associated with a SNP near the APOA5-APOA4-APOC3-APOA1 gene cluster on chromosome 11q23 linked in the Amish to the APOC3 R19X null mutation. On 6q locus, we detected associations of Lp(a)-cholesterol with 118 common variants (P = 5 × 10(-8) to 3.91 × 10(-19)) spanning a ∼5.3 Mb region that included the LPA gene. To further elucidate variation within LPA, we sequenced LPA and identified two variants most strongly associated with Lp(a)-cholesterol, rs3798220 (P = 1.07 × 10(-14)) and rs10455872 (P = 1.85 × 10(-12)). We also measured copy numbers of kringle IV-2 (KIV-2) in LPA using qPCR. KIV-2 numbers were significantly associated with Lp(a)-cholesterol (P = 2.28 × 10(-9)). Conditional analyses revealed that rs3798220 and rs10455872 were associated with Lp(a)-cholesterol levels independent of each other and KIV-2 copy number. Furthermore, we determined for the first time that levels of LPA mRNA were higher in the carriers than non-carriers of rs10455872 (P = 0.0001) and were not different between carriers and non-carriers of rs3798220. Protein levels of apo(a) were higher in the carriers than non-carriers of both rs10455872 and rs3798220. In summary, we identified multiple independent genetic determinants for Lp(a)-cholesterol. These findings provide new insights into Lp(a) regulation.
Lu, Wensheng; Cheng, Yu-Ching; Chen, Keping; Wang, Hong; Gerhard, Glenn S.; Still, Christopher D.; Chu, Xin; Yang, Rongze; Parihar, Ankita; O'Connell, Jeffrey R.; Pollin, Toni I.; Angles-Cano, Eduardo; Quon, Michael J.; Mitchell, Braxton D.; Shuldiner, Alan R.; Fu, Mao
Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related events that is under strong genetic control (heritability = 0.68–0.98). However, causal mutations and functional validation of biological pathways modulating Lp(a) metabolism are lacking. We performed a genome-wide association scan to identify genetic variants associated with Lp(a)-cholesterol levels in the Old Order Amish. We confirmed a previously known locus on chromosome 6q25-26 and found Lp(a) levels also to be significantly associated with a SNP near the APOA5–APOA4–APOC3–APOA1 gene cluster on chromosome 11q23 linked in the Amish to the APOC3 R19X null mutation. On 6q locus, we detected associations of Lp(a)-cholesterol with 118 common variants (P = 5 × 10−8 to 3.91 × 10−19) spanning a ∼5.3 Mb region that included the LPA gene. To further elucidate variation within LPA, we sequenced LPA and identified two variants most strongly associated with Lp(a)-cholesterol, rs3798220 (P = 1.07 × 10−14) and rs10455872 (P = 1.85 × 10−12). We also measured copy numbers of kringle IV-2 (KIV-2) in LPA using qPCR. KIV-2 numbers were significantly associated with Lp(a)-cholesterol (P = 2.28 × 10−9). Conditional analyses revealed that rs3798220 and rs10455872 were associated with Lp(a)-cholesterol levels independent of each other and KIV-2 copy number. Furthermore, we determined for the first time that levels of LPA mRNA were higher in the carriers than non-carriers of rs10455872 (P = 0.0001) and were not different between carriers and non-carriers of rs3798220. Protein levels of apo(a) were higher in the carriers than non-carriers of both rs10455872 and rs3798220. In summary, we identified multiple independent genetic determinants for Lp(a)-cholesterol. These findings provide new insights into Lp(a) regulation. PMID:25575512
De Pergola, Giovanni; Triggiani, Vincenzo; Bartolomeo, Nicola; Nardecchia, Adele; Giagulli, Vito Angelo; Bruno, Irene; Caccavo, Domenico; Silvestris, Franco
Osteocalcin, a protein synthesized by osteoblasts during the bone formation phase of bone remodeling, is used as a biomarker for the bone production process, and its serum levels are positively correlated with bone mineral density during treatment with anabolic bone drugs for osteoporosis. Higher fat mass has been shown to be a risk factor for osteoporosis and fragility fractures and body fat and bone interplay through several adipokines and bone-derived molecules, regulating bone remodeling, adipogenesis, body weight control, and glucose homeostasis. The aim of this study was to evaluate the relationship between total osteocalcin levels and obesity, hypertension and type 2 diabetes. The present study was performed in a cohort of 298 patients including a) 121 overweight and obese patients, unaffected by hypertension or type 2 diabetes, b) 129 subjects affected by hypertension and not by type 2 diabetes, and c) 48 subjects affected by both hypertension and type 2 diabetes. No subject of the group of overweight and obese patients was taking any kind of drug. All patients affected by hypertension, with or without type 2 diabetes, were taking drugs for hypertension. Examining only patients affected by type 2 diabetes (n: 48), 43 (90% of all) were taking drugs to reduce blood glucose levels, 26 (54% of all) were taking drugs to reduce cholesterol levels (statins and/or ezetimide, etc), and 4 (8% of all) were taking ω-3 for hypertriglyceridemia. Each patient was evaluated for anthropometric measurements as well as for serum osteocalcin and uric acid, and plasma glucose, HbA1c, and lipid determination. Osteocalcin levels were significantly and negatively associated with BMI, waist circumference, and HbA1c, and significantly and positively correlated with HDL-cholesterol and systolic blood pressure in the whole population. Osteocalcin levels did maintain an independent negative association with BMI, and HbA1c, and positive association with HDL cholesterol and systolic
Eriksson, Marie; Forslund, Ann-Sofi; Jansson, Jan-Håkan; Söderberg, Stefan; Wennberg, Maria; Eliasson, Mats
Aim Decreasing cholesterol levels in Western populations is the main reason for decreasing mortality due to coronary heart disease. Our aim was to analyze trends in cholesterol levels in the population during a period of 20 years in relation to previous cardiovascular disease (CVD), other cardiovascular risk factors, and socioeconomic status. Methods and results A total of 4546 women and 4349 men aged 25–74 years participated in five population-based surveys in the Northern Sweden MONICA Study between 1994 and 2014 (participation rate 76.8–62.5%). Total cholesterol levels decreased from 6.2 mmol/L (95% confidence interval, CI, 6.1–6.2) in 1994 to 5.5 mmol/L (CI 5.4–5.5) in 2014. The decrease was more pronounced in elderly vs. younger participants (1.0 vs. 0.5 mmol/L). In 2014, participants with previous CVD, diabetes, or hypertension had lower cholesterol levels than the general population, whereas their levels were higher or similar to the general population in 1994. The use of lipid-lowering drugs increased markedly and was used by 14.3% in 2014. Previously described differences in cholesterol levels between participants with obesity and normal weight, and between those with and without university education, diminished, or vanished over time. Conclusion Cholesterol levels decreased by 0.7 mmol/L over 20 years with no sign of abating. The improvement occurred in all age and gender groups but more prominently among those at high risk of ischaemic heart disease. PMID:26941200
Eriksson, Marie; Forslund, Ann-Sofi; Jansson, Jan-Håkan; Söderberg, Stefan; Wennberg, Maria; Eliasson, Mats
Decreasing cholesterol levels in Western populations is the main reason for decreasing mortality due to coronary heart disease. Our aim was to analyze trends in cholesterol levels in the population during a period of 20 years in relation to previous cardiovascular disease (CVD), other cardiovascular risk factors, and socioeconomic status. A total of 4546 women and 4349 men aged 25-74 years participated in five population-based surveys in the Northern Sweden MONICA Study between 1994 and 2014 (participation rate 76.8-62.5%). Total cholesterol levels decreased from 6.2 mmol/L (95% confidence interval, CI, 6.1-6.2) in 1994 to 5.5 mmol/L (CI 5.4-5.5) in 2014. The decrease was more pronounced in elderly vs. younger participants (1.0 vs. 0.5 mmol/L). In 2014, participants with previous CVD, diabetes, or hypertension had lower cholesterol levels than the general population, whereas their levels were higher or similar to the general population in 1994. The use of lipid-lowering drugs increased markedly and was used by 14.3% in 2014. Previously described differences in cholesterol levels between participants with obesity and normal weight, and between those with and without university education, diminished, or vanished over time. Cholesterol levels decreased by 0.7 mmol/L over 20 years with no sign of abating. The improvement occurred in all age and gender groups but more prominently among those at high risk of ischaemic heart disease. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.
Mandoj, Chiara; Renna, Rosaria; Plantone, Domenico; Sperduti, Isabella; Cigliana, Giovanni; Conti, Laura; Koudriavtseva, Tatiana
So far, no studies have been conducted to evaluate possible correlations between lipid/lipoprotein levels and the anti-phospholipid antibody (aPL) positivity in multiple sclerosis (MS). In this cross-sectional study, we aimed to investigate the relationships between serum lipid profile and aPL positivity rates in MS patients, and their possible differences among secondary-progressive MS (SPMS) patients, relapsing-remitting MS patients in remission (REM) and in relapse (REL). We included 16 SPMS, 58 REM and 26 REL. Their sera were tested for aPL (anti-cardiolipin, anti-β2glycoproteinI, anti-prothrombin, anti-annexinV), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein(a) levels. High TC levels were more frequent in SPMS patients than other groups (p=0.05). The REL had significantly higher rates of positivity for anti-β2glycoproteinI IgM (p<0.0001), anti-prothrombin IgG and IgM (both p=0.05) than the other groups. A significant positive correlation was found between age and both TC and LDL-C, disability and both TC and LDL-C, disease duration and LDL-C. TC levels were significantly higher (p=0.007) in anti-annexinV-IgG positive patients. The anti-annexinV-IgG positivity significantly associated with high levels of TC (p=0.002) and LDL-C (p=0.03). Our results support the hypothesis that both thrombogenic and neurodegenerative mechanisms associated with an abnormal cholesterol homeostasis might contribute to MS progression. Our study may have interesting practical implications, which could potentially open new therapeutic approaches in the context of appropriately designed clinical trials. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Al Rajabi, Ala; Castro, Gabriela S F; da Silva, Robin P; Nelson, Randy C; Thiesen, Aducio; Vannucchi, Helio; Vine, Donna F; Proctor, Spencer D; Field, Catherine J; Curtis, Jonathan M; Jacobs, René L
Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development
Shen, Meng-Chieh; Quinlivan, Vanessa; Anderson, Jennifer L.; Farber, Steven A.
ABSTRACT Caveolae and their structural protein caveolin 1 (CAV1) have roles in cellular lipid processing and systemic lipid metabolism. Global deletion of CAV1 in mice results in insulin resistance and increases in atherogenic plasma lipids and cholesterol, but protects from diet-induced obesity and atherosclerosis. Despite the fundamental role of the intestinal epithelia in the regulation of dietary lipid processing and metabolism, the contributions of CAV1 to lipid metabolism in this tissue have never been directly investigated. In this study the cellular dynamics of intestinal Cav1 were visualized in zebrafish and the metabolic contributions of CAV1 were determined with mice lacking CAV1 in intestinal epithelial cells (CAV1IEC-KO). Live imaging of Cav1–GFP and fluorescently labeled caveolae cargos shows localization to the basolateral and lateral enterocyte plasma membrane (PM), suggesting Cav1 mediates transport between enterocytes and the submucosa. CAV1IEC-KO mice are protected from the elevation in circulating fasted low-density lipoprotein (LDL) cholesterol associated with a high-fat diet (HFD), but have increased postprandial LDL cholesterol, total free fatty acids (FFAs), palmitoleic acid, and palmitic acid. The increase in circulating FAs in HFD CAV1IEC-KO mice is mirrored by decreased hepatic FAs, suggesting a non-cell-autonomous role for intestinal epithelial cell CAV1 in promoting hepatic FA storage. In conclusion, CAV1 regulates circulating LDL cholesterol and several FA species via the basolateral PM of enterocytes. These results point to intestinal epithelial cell CAV1 as a potential therapeutic target to lower circulating FFAs and LDL cholesterol, as high levels are associated with development of type II diabetes and cardiovascular disease. PMID:28130355
Mumford, Sunni L.; Schisterman, Enrique F.; Siega-Riz, Anna Maria; Gaskins, Audrey J.; Wactawski-Wende, Jean; VanderWeele, Tyler J.
High-fiber diets are associated with improved lipid profiles. However, pre- and postmenopausal women respond differently to fiber intake, suggesting that endogenous estradiol mediates the effect. The authors' objective was to determine the direct effect of fiber intake on lipoprotein cholesterol levels independent of estradiol among premenopausal women. The BioCycle Study, a prospective cohort study conducted at the State University of New York at Buffalo from 2005 to 2007, followed 259 healthy women for up to 2 complete menstrual cycles. Serum lipoprotein and hormone levels were measured at 16 visits timed using fertility monitors. Fiber intake was assessed by 8 24-hour recalls. Marginal structural models with inverse probability weights for both lipoprotein and estradiol levels were used to estimate controlled direct effects of the highest category of fiber intake (≥22 g/day vs. <22 g/day) while accounting for age, body mass index, total energy, vitamin E intake, physical activity, luteinizing hormone, follicle-stimulating hormone, and progesterone. Reductions were observed in total and low density lipoprotein cholesterol in women with higher fiber intakes. Direct effects were greater than total effects. These analyses suggested that estradiol mediates at least part of the association between fiber and cholesterol among premenopausal women. More research is needed to elucidate the biologic mechanisms driving these associations. PMID:21148240
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...
Wones, R G; Kerman, K M; Hissa, D C; Meloy, N; Stein, E A
Total and high-density lipoprotein (HDL) cholesterol levels of 2,387 adults were screened at a worksite and a bloodbank. Hypothetical referral decisions were made according to three sets of guidelines: the 1984 National Institutes of Health Consensus Conference guidelines (NIHCC), a single referral cutpoint of 5.2 millimoles per liter (mmol per L), and the current National Cholesterol Education Program (NCEP) guidelines for screening in physicians' office. Under the NIHCC guidelines, 31 percent of the participants would have been referred to their physicians, 32 percent under the NCEP guidelines, and 56 percent would have been referred had the 5.2 mmol per L cutpoint been used. Twenty-four percent of the participants would have been referred under both the NIHCC and NCEP guidelines; 7 percent would have been referred under the NIHCC guidelines, but not the NCEP's. Eight percent would have been referred under the NCEP guidelines, but not the NIHCC's. Those who would have been referred were older, and more likely to be male and to have low levels of HDL cholesterol than the 7 percent who would have been referred under NIHCC guidelines only. All of the 8 percent had coronary heart disease, or two or more other coronary risk factors, whereas none of the 7 percent did. If low HDL had been used as a risk factor under NCEP guidelines, the number of persons referred would have increased slightly (to 34 percent) and low HDL levels would have become one of the most prevalent risk factors. The researchers concluded that public cholesterol screening programs should use the NCEP guidelines (with or without HDL), rather than the NIHCC guidelines, or a single 5.2 mmol per L cutpoint. PMID:2508171
Baer, J T
Eighty management-level male employees participated in a company-sponsored comprehensive physical that included determination of plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels and percentage of body fat. After the lipid screening, each employee met with a registered dietitian who explained the results of the lipid analysis and discussed risk factors for coronary heart disease with an emphasis on diet. Seventy employees had a triglyceride level above 5.17 mmol/L and were invited to participate in a nutrition education program. Thirty-three (mean age = 44 years) chose to participate (intervention group); the other 37 (mean age = 35 years) served as controls (control group). Thus, the design of the study was not random. All subjects completed 3-day dietary records before and after the nutrition education program. Nutrition intervention consisted of (a) individualized instruction about the step 1 diet; (b) group sessions (1 hour every 3 months) on eating out, dietary fiber, and maintaining heart healthy behaviors; and (c) individualized follow-up by telephone (one call per month). The results of the year-long program revealed that men in the intervention group decreased dietary intake of energy (2,546 +/- 162 kcal to 2,246 +/- 125 kcal) and cholesterol (444 +/- 5.3 mg to 304 +/- 1.6 mg) and percentage of energy from total fat (38 +/- 3.4% to 31 +/- 2.6%) and protein (24 +/- 3.5% to 20 +/- 2.2%). Their consumption of carbohydrate and dietary fiber increased (38 +/- 2.1% to 45 +/- 2.5% and 8.0 +/- 2.3 g to 23.0 +/- 3.5 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Weingärtner, Oliver; Bogeski, Ivan; Kummerow, Carsten; Schirmer, Stephan H; Husche, Constanze; Vanmierlo, Tim; Wagenpfeil, Gudrun; Hoth, Markus; Böhm, Michael; Lütjohann, Dieter; Laufs, Ulrich
This double-blind, randomized, placebo-controlled, cross-over intervention-study was conducted in healthy volunteers to evaluate the effects of plant sterol ester supplemented margarine on cholesterol, non-cholesterol sterols and oxidative stress in serum and monocytes. Sixteen volunteers, average age 34 years, with no or mild hypercholesterolemia were subjected to a 4 week period of daily intake of 3g plant sterols per day supplied via a supplemented margarine on top of regular eating habits. After a wash-out period of one week, volunteers switched groups. Compared to placebo, a diet supplementation with plant sterols increased serum levels of plant sterols such as campesterol (+0.16±0.19mg/dL, p=0.005) and sitosterol (+0.27±0.18mg/dL, p<0.001) and increased markers of cholesterol synthesis such as desmosterol (+0.05±0.07mg/dL, p=0.006) as well as lathosterol (+0.11±0.16mg/dL, p=0.012). Cholesterol serum levels, however, were not changed significantly (+18.68±32.6mg/dL, p=0.052). These findings could not be verified in isolated circulating monocytes. Moreover, there was no effect on monocyte activation and no differences with regard to redox state after plant sterol supplemented diet. Therefore, in a population of healthy volunteers with no or mild hypercholesterolemia, consumption of plant sterol ester supplemented margarine results in increased concentrations of plant sterols and cholesterol synthesis markers without affecting total cholesterol in the serum, activation of circulating monocytes or redox state. Copyright © 2016 Elsevier Ltd. All rights reserved.
He, Lianping; Qian, Yifan; Ren, Xiaohua; Jin, Yuelong; Chang, Weiwei; Li, Jie; Chen, Yan; Song, Xiuli; Tang, Hui; Ding, Lingling; Guo, Daoxia; Yao, Yingshui
Our previous studies showed that serum calcium level may have influence in the blood pressure to older male subjects, but the relationship between serum calcium level and blood lipids is unclear. The aim of this study was to evaluate the relationship between total serum calcium level and blood lipids. In our study, total serum calcium level and blood lipids were measured among 1,075 subjects, with age range of 30-60 years, who were recruited for the routine health screening in 2006. The results showed that serum calcium level was positively correlated with triglyceride and total cholesterol weight, but not HDL-cholesterol and LDL-cholesterol in female subjects (P < 0.05). No correlation was found between total serum calcium level and blood lipids in male subjects (P > 0.05). These findings suggest that a higher total serum calcium level may have a adverse effects on serum cholesterol and triglycerides among female subjects.
Hashimoto, Naoto; Ito, Yusaku; Han, Kyu-Ho; Shimada, Ken-ichiro; Sekikawa, Mitsuo; Topping, David L; Bird, Anthony R; Noda, Takahiro; Chiji, Hideyuki; Fukushima, Michihiro
In our previous study, we demonstrated that retrograded starch, a kind of resistant starch, of beans reduced serum lipid levels in rats. In this study, we examined whether retrograded starch in potato pulps could reduce serum lipid concentrations. Rats were given diets containing 15 g of retrograded starch in potato pulps from the Benimaru potato (BM) or Hokkaikogane potato (HK) in a 100 g diet for 4 wk. At the 4th week, the total cholesterol level in the serum in the BM group and serum triglyceride (TG) level in the HK group were significantly lower than those in the control group. In the BM group, the contents of fecal bile acids were significantly higher than those in the control group. On the other hand, in the HK group, the hepatic mRNA level of fatty acid synthase (FAS) was significantly lower than that in the control group. The FAS mRNA level correlated with the mRNA level of sterol regulatory element-binding protein-1c (SREBP-1c), a regulator of expression of FAS, positively. These results suggested that BM pulp promoted the excretion of bile acids, which resulted in a low concentration of serum cholesterol. On the other hand, HK pulp inhibited the synthesis of fatty acids at the mRNA levels of FAS and SREBP-1c, which might lead to a reduction of the serum TG level.
Kammerer, Candace M.; Rainwater, David L.; Gouin, Nicolas; Jasti, Madhuri; Douglas, Kory C.; Dressen, Amy S.; Ganta, Prasanth; VandeBerg, John L.; Samollow, Paul B.
Plasma cholesterol levels among individuals vary considerably in response to diet. However, the genes that influence this response are largely unknown. Non-HDL (V+LDL) cholesterol levels vary dramatically among gray, short-tailed opossums fed an atherogenic diet, and we previously reported that two quantitative trait loci (QTLs) influenced V+LDL cholesterol on two diets. We used hypothesis-free, genome-wide linkage analyses on data from 325 pedigreed opossums and located one QTL for V+LDL cholesterol on the basal diet on opossum chromosome 1q [logarithm of the odds (LOD) = 3.11, genomic P = 0.019] and another QTL for V+LDL on the atherogenic diet (i.e., high levels of cholesterol and fat) on chromosome 8 (LOD = 9.88, genomic P = 5 × 10−9). We then employed a novel strategy involving combined analyses of genomic resources, expression analysis, sequencing, and genotyping to identify candidate genes for the chromosome 8 QTL. A polymorphism in ABCB4 was strongly associated (P = 9 × 10−14) with the plasma V+LDL cholesterol concentrations on the high-cholesterol, high-fat diet. The results of this study indicate that genetic variation in ABCB4, or closely linked genes, is responsible for the dramatic differences among opossums in their V+LDL cholesterol response to an atherogenic diet. PMID:20650928
Kammerer, Candace M; Rainwater, David L; Gouin, Nicolas; Jasti, Madhuri; Douglas, Kory C; Dressen, Amy S; Ganta, Prasanth; Vandeberg, John L; Samollow, Paul B
Plasma cholesterol levels among individuals vary considerably in response to diet. However, the genes that influence this response are largely unknown. Non-HDL (V+LDL) cholesterol levels vary dramatically among gray, short-tailed opossums fed an atherogenic diet, and we previously reported that two quantitative trait loci (QTLs) influenced V+LDL cholesterol on two diets. We used hypothesis-free, genome-wide linkage analyses on data from 325 pedigreed opossums and located one QTL for V+LDL cholesterol on the basal diet on opossum chromosome 1q [logarithm of the odds (LOD) = 3.11, genomic P = 0.019] and another QTL for V+LDL on the atherogenic diet (i.e., high levels of cholesterol and fat) on chromosome 8 (LOD = 9.88, genomic P = 5 x 10(-9)). We then employed a novel strategy involving combined analyses of genomic resources, expression analysis, sequencing, and genotyping to identify candidate genes for the chromosome 8 QTL. A polymorphism in ABCB4 was strongly associated (P = 9 x 10(-14)) with the plasma V+LDL cholesterol concentrations on the high-cholesterol, high-fat diet. The results of this study indicate that genetic variation in ABCB4, or closely linked genes, is responsible for the dramatic differences among opossums in their V+LDL cholesterol response to an atherogenic diet.
Akbari, Hamed; Mirzaei, Ramazan; Nasrabadi, Tahereh; Gholami-Fesharaki, Mohammad
Background: Working outside daylight hours (7 am to 7 pm) is called shift work. Shift work is a common practice in many industries and factories such as steel industries, petroleum industries, power plants, and in some services such as medicine and nursing and police forces, in which professionals provide services during day and night. Objectives: Considering the contradictory reports of different studies, we decided to evaluate the effect of shift work on cholesterol and triglyceride (TG) levels through a historical cohort on steel industry workers. Patients and Methods: This retrospective cohort study was performed on all the staff of Isfahan’s Mobarakeh Steel Company between years 2002 and 2011. There were 5773 participants in this study. Data were collected from the medical records of the staff using the census method. For analysis of data, generalized estimating equation (GEE) regression was used. Results: The results showed a significant difference in cholesterol levels between shift workers and day workers on the first observation (P < 0.001), yet no such difference was observed for TG (P = 0.853). Moreover, the results showed that the variables of age, work experience and BMI were not similar between shift workers and day workers. Therefore, to remove the effect of such variables, we used GEE regression. Despite the borderline difference of cholesterol between regular shift workers and day workers, this correlation was not statistically significant (P = 0.051). The results for TG also showed no correlation with shift work. Conclusions: According to the findings of this study, there is no relationship between shift work and changes in serum TG and cholesterol. The lack of relationship can be due to shift plans for shift workers, nutrition, or the “Healthy Heart project” at Isfahan Mobarakeh Steel Company. PMID:25763276
Andreadou, Ioanna; Benaki, Dimitra; Efentakis, Panagiotis; Bibli, Sofia-Iris; Milioni, Alkistis-Ioanna; Papachristodoulou, Anastasia; Zoga, Anastasia; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Iliodromitis, Efstathios K
Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5 % dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5 % dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg × kg(-1) × day(-1). All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol
Fessler, Michael B.; Jaramillo, Renee; Crockett, Patrick W.; Zeldin, Darryl C.
Background Cholesterol promotes Th2 immunity and allergic inflammation in rodents; whether this occurs in humans is unclear. Reports of both direct and inverse associations between serum cholesterol and atopy in different populations suggest that race and/or other demographic variables may modify these relationships. Aims of the study To determine relationships between levels of three serum cholesterol measures (total cholesterol [TC], high density lipoprotein-cholesterol [HDL-C], and non-HDL-C), and atopy in a sample representative of the U.S. population. Methods Cross-sectional study of 6,854 participants aged ≥6 years from the 2005-2006 National Health and Nutrition Examination Survey. Results In the overall population, adjusted odds ratios (AORs) per 2-standard deviation increase of TC and non-HDL-C for biochemical atopy (defined as ≥1 allergen-specific IgE to 19 allergens) were 1.17 (95% confidence interval [CI], 1.00-1.38) and 1.19 (95% CI, 1.03-1.39), respectively. Interactions by race were noted for the two relationships (interaction p=0.004 and p=0.009, respectively), with non-Hispanic Whites (NHWs) having direct relationships (TC: AOR 1.27 [95% CI, 1.03-1.57]; non-HDL-C: AOR 1.27 [95% CI, 1.03-1.56]) and non-Hispanic Blacks (NHBs) inverse relationships (TC: AOR 0.77 [95% CI, 0.62-0.95]; non-HDL-C: AOR 0.86 [95% CI, 0.69-1.08]). The adjusted HDL-C-atopy relationship was nonsignificant for NHWs and inverse for NHBs (AOR 0.77 [95% CI, 0.61-0.96]). Relationships were independent of body mass index and serum C-reactive protein, and unmodified by corticosteroid or statin usage. Results were similar using current hay fever/allergy as the atopy outcome. Conclusions There are marked inter-racial differences in the relationship between serum cholesterol and atopy in the U.S population. PMID:20015326
Kim, Mi Kyung; Cho, Sang Woon; Park, Yoo Kyoung
Excessive oxidative stress and abnormal blood lipids may cause chronic diseases. This risk can be reduced by consuming an antioxidant- and fiber-rich vegetarian diet. We compared biomarkers of oxidative stress, antioxidant capacity, and lipid profiles of sex- and age-matched long-term vegetarians and omnivores in Korea. Forty-five vegetarians (23 men and 22 women; mean age, 49.5 ± 5.3 years), who had maintained a vegetarian diet for a minimum of 15 years, and 30 omnivores (15 men and 15 women; mean age, 48.9 ± 3.6 years) participated in this study. Their 1-day, 24-h recall, and 2-day dietary records were analyzed. Oxidative stress was measured by the levels of diacron reactive oxygen metabolites (d-ROM). Antioxidant status was determined by the biological antioxidant potential (BAP) and levels of endogenous antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. We observed that vegetarians had a significantly lower body fat percentage (21.6 ± 6.4%) than that of omnivores (25.4 ± 4.6%; P < 0.004). d-ROM levels were significantly lower in vegetarians than those in omnivores (331.82 ± 77.96 and 375.80 ± 67.26 Carratelli units; P < 0.011). Additionally, total cholesterol levels in the vegetarians and omnivores were 173.73 ± 31.42 mg/dL and 193.17 ± 37.89 mg/dL, respectively (P < 0.018). Low-density lipoprotein cholesterol was 101.36 ± 23.57 mg/dL and 120.60 ± 34.62 mg/dL (P < 0.005) in the vegetarians and omnivores, respectively, indicating that vegetarians had significantly lower lipid levels. Thus, oxidative stress, body fat, and cholesterol levels were lower in long-term vegetarians than those in omnivores.
Kim, Mi Kyung; Cho, Sang Woon
Excessive oxidative stress and abnormal blood lipids may cause chronic diseases. This risk can be reduced by consuming an antioxidant- and fiber-rich vegetarian diet. We compared biomarkers of oxidative stress, antioxidant capacity, and lipid profiles of sex- and age-matched long-term vegetarians and omnivores in Korea. Forty-five vegetarians (23 men and 22 women; mean age, 49.5 ± 5.3 years), who had maintained a vegetarian diet for a minimum of 15 years, and 30 omnivores (15 men and 15 women; mean age, 48.9 ± 3.6 years) participated in this study. Their 1-day, 24-h recall, and 2-day dietary records were analyzed. Oxidative stress was measured by the levels of diacron reactive oxygen metabolites (d-ROM). Antioxidant status was determined by the biological antioxidant potential (BAP) and levels of endogenous antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. We observed that vegetarians had a significantly lower body fat percentage (21.6 ± 6.4%) than that of omnivores (25.4 ± 4.6%; P < 0.004). d-ROM levels were significantly lower in vegetarians than those in omnivores (331.82 ± 77.96 and 375.80 ± 67.26 Carratelli units; P < 0.011). Additionally, total cholesterol levels in the vegetarians and omnivores were 173.73 ± 31.42 mg/dL and 193.17 ± 37.89 mg/dL, respectively (P < 0.018). Low-density lipoprotein cholesterol was 101.36 ± 23.57 mg/dL and 120.60 ± 34.62 mg/dL (P < 0.005) in the vegetarians and omnivores, respectively, indicating that vegetarians had significantly lower lipid levels. Thus, oxidative stress, body fat, and cholesterol levels were lower in long-term vegetarians than those in omnivores. PMID:22586505
Low and moderate-fat plant sterol fortified soymilk in modulation of plasma lipids and cholesterol kinetics in subjects with normal to high cholesterol concentrations: report on two randomized crossover studies
Rideout, Todd C; Chan, Yen-Ming; Harding, Scott V; Jones, Peter JH
Background Although consumption of various plant sterol (PS)-enriched beverages is effective in lowering plasma cholesterol, the lipid-lowering potential of PS in a soymilk format has not been investigated thoroughly. Therefore, to evaluate the efficacy of PS-enriched soy beverages on plasma lipids and cholesterol kinetics, we conducted two separate 28 d dietary controlled cross-over studies. In study 1, the cholesterol-lowering efficacy of a low-fat (2 g/serving) PS enriched soy beverage was examined in 33 normal cholesterolemic subjects in comparison with 1% dairy milk. In study 2, we investigated the efficacy of a moderate-fat (3.5 g/serving) PS-enriched soy beverage on plasma cholesterol concentrations and cholesterol kinetic responses in 23 hypercholesterolemic subjects compared with 1% dairy milk. Both the low and moderate-fat PS-enriched soymilk varieties provided 1.95 g PS/d. Endpoint plasma variables were analyzed by repeated-measures ANOVA using baseline values as covariates for plasma lipid measurements. Results In comparison with the 1% dairy milk control, the low-fat soy beverage reduced (P < 0.05) total and LDL-cholesterol by 10 and 13%, respectively. Consumption of the moderate-fat PS-enriched soy beverage reduced (P < 0.05) plasma total and LDL-cholesterol by 12 and 15% respectively. Fasting triglycerides were reduced by 9.4% following consumption of the moderate-fat soy beverage in comparison with the 1% dairy milk. Both low and moderate-fat PS-enriched soy varieties reduced (P < 0.05) LDL:HDL and TC:HDL ratios compared with the 1% dairy milk control. Consumption of the moderate-fat PS-enriched soymilk reduced (P < 0.05) cholesterol absorption by 27%, but did not alter cholesterol synthesis in comparison with 1% dairy milk. Conclusion We conclude that, compared to 1% dairy milk, consumption of low and moderate-fat PS-enriched soy beverages represents an effective dietary strategy to reduce circulating lipid concentrations in normal to
Jeong, Sang Chul; Jeong, Yong Tae; Yang, Byung Keun; Islam, Rezuanul; Koyyalamudi, Sundar Rao; Pang, Gerald; Cho, Kai Yip; Song, Chi Hyun
Agaricus bisporus (white button mushroom; WBM) contains high levels of dietary fibers and antioxidants including vitamin C, D, and B(12); folates; and polyphenols that may provide beneficial effects on cardiovascular and diabetic diseases. The objective of this study was to examine the hypothesis that intake of the fruiting bodies of WBM regulates anticholesterolemic and antiglycemic responses in rats fed a hypercholesterolemic diet (0.5% cholesterol; 14% fat) and rats with type 2 diabetes induced by injection of streptozotocin (STZ) (50 mg/kg body weight), respectively. The STZ-induced diabetic male Sprague-Dawley rats fed the Agaricus bisporus powder (ABP; 200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose and triglyceride (TG) concentrations (24.7% and 39.1%, respectively), liver enzyme activities, alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%, respectively), and liver weight gain (P < .05). In hypercholesterolemic rats, oral feeding of ABP for 4 weeks resulted in a significant decrease in plasma total cholesterol (TC) and low-density lipoprotein (LDL) (22.8% and 33.1%, respectively) (P < .05). A similar significant decrease in hepatic cholesterol and TG concentrations was observed (36.2% and 20.8%, respectively) (P < .05). Decrease in TC, LDL, and TG concentrations was accompanied by a significant increase in plasma high-density lipoprotein concentrations. It was concluded that A bisporus mushroom had both hypoglycemic and hypolipidemic activity in rats.
Nervi, F; Bronfman, M; Allalón, W; Depiereux, E; Del Pozo, R
Although the significance of the enterohepatic circulation of bile salts in the solubilization and biliary excretion of cholesterol is well established, little is known about the intrahepatic determinants of biliary cholesterol output. Studies were undertaken to elucidate some of these determinants in the rat. Feeding 1% diosgenin for 1 wk increased biliary cholesterol output and saturation by 400%. Bile flow, biliary bile salt, phospholipid and protein outputs remained in the normal range. When ethynyl estradiol (EE) was injected into these animals, biliary cholesterol output decreased to almost normal levels under circumstances of minor changes in the rates of biliary bile salt and phospholipid outputs. Similarly, when chylomicron cholesterol was intravenously injected into diosgenin-fed animals, biliary cholesterol output significantly decreased as a function of the dose of chylomicron cholesterol administered. Relative rates of hepatic cholesterol synthesis and esterification were measured in isolated hepatocytes. Although hepatic cholesterogenesis increased 300% in diosgenin-fed animals, the contribution of newly synthesized cholesterol to total biliary cholesterol output was only 19 +/- 9%, compared with 12 +/- 6% in control and 15 +/- 5% in diosgenin-fed and EE-injected rats. The rate of oleate incorporation into hepatocytic cholesterol esters was 30% inhibited in diosgenin-fed rats. When EE was injected into these animals, the rate of cholesterol esterification increased to almost 300%. To investigate further the interrelationship between hepatic cholesterol esterification and biliary cholesterol output, we studied 21 diosgenin-fed rats. Six of them received in addition EE and 10 received chylomicron cholesterol. The relationships between biliary cholesterol output as a function of both microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity and hepatic cholesterol ester concentration were significantly correlated in a reciprocal manner. From these
... Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; Cardiac Risk Assessment ; Lp-PLA2 All content on ... HDL-C) is used as part of a lipid profile to screen for unhealthy levels of lipids and ...
... Do My Cholesterol Levels Mean? | Spanish Your Cholesterol Score Explained What Are High Blood Cholesterol and Triglycerides? ... Pressure? 7 All About Heart Rate (Pulse) 8 Warning Signs of a Heart Attack 9 Tachycardia | Fast ...
Calleros, Laura; Lasa, Marina; Toro, María J; Chiloeches, Antonio
Cholesterol, p38 MAPK and NFkappaB have been shown to participate in inflammation and cellular differentiation. Here, we examined the effect of cholesterol on NFkappaB-dependent transcription and the mechanisms underlying this effect in NIH3T3 cells. We show that chronic cholesterol depletion achieved with lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment resulted in a significant increase in NFkappaB-dependent transcription, NFkappaB-DNA binding, IkappaBalpha degradation and p65/NFkappaB translocation to the nucleus, and the addition of exogenous cholesterol reversed these effects. Previously, we have shown that low cell cholesterol levels activate p38 MAPK. Here, we found that inhibition of p38 MAPK with the specific inhibitor SB203580 blocked the increase in NFkappaB activity, IkappaBalpha degradation and p65/NFkappaB translocation to the nucleus induced by cholesterol depletion. Moreover, the inhibition of the p38 MAPK downstream effector MSK1 with the specific inhibitor H89, or the overexpression of a kinase defective MSK1 abrogated the NFkappaB-dependent transcription induced by cholesterol depletion. On the other hand, the transactivation potential of p65/NFkappaB depends on phosphorylation of S276 by MSK1. We observed that cholesterol depletion increased the p65/NFkappaB transactivation capacity. This effect was reversed by cell cholesterol repletion or incubation with the SB203580 inhibitor. Moreover, the expression of a p65/NFkappaB S276A mutant was insensitive to cholesterol depletion. Together, our results demonstrate that cholesterol depletion induces NFkappaB transcriptional activity, not only by affecting the IkappaBalpha degradation and the translocation of p65/NFkappaB to the nucleus, but also regulating the p65/NFkappaB transactivating potential through a p38 MAPK/MSK1 mediated pathway.
Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun
Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice.
Kuder, Craig H; Weivoda, Megan M; Zhang, Ying; Zhu, Junjia; Neighbors, Jeffrey D; Wiemer, David F; Hohl, Raymond J
The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3-deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X-receptor (LXR) activation. The effects of 3dSB on ATP-binding cassette transporter 1 levels and other LXR targets are similar to that of 25-hydroxycholesterol, an LXR agonist. Unlike 25-hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.
Paavola, Timo; Kuusisto, Sanna; Jauhiainen, Matti; Kakko, Sakari; Kangas-Kontio, Tiia; Metso, Jari; Soininen, Pasi; Ala-Korpela, Mika; Bloigu, Risto; Hannuksela, Minna L; Savolainen, Markku J; Salonurmi, Tuire
The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001). Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed.
Paavola, Timo; Kuusisto, Sanna; Jauhiainen, Matti; Kakko, Sakari; Kangas-Kontio, Tiia; Metso, Jari; Soininen, Pasi; Ala-Korpela, Mika; Bloigu, Risto; Hannuksela, Minna L.; Savolainen, Markku J.
Objective The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. Methods HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. Results While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001). Conclusion Our results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed. PMID:28207870
Toe valuate whether dietary fats of different degrees of unsaturation alter glucose and very low density lipoprotein-cholesterol (VLDL-CH) homeostasis, normal and alloxan-diabetic pigs were fed diets containing either beef tallow or soy oil as the primary source of fat for 6 weeks. After intra-arterial and oral doses of glucose, pigs fed soy oil had similar glucose and greater insulin concentrations in plasma when compared with pigs fed beef tallow. Beef tallow-fed pigs additionally were 40% more glucose effective than were soy oil-fed pigs. Disappearance of injected autologous /sup 14/C-VLDL-CH was analyzed in pigs using a two-pool model. Diabetes resulted in a twofold increase in half-lives and a 60-fold increase in pool sizes of the primary and secondary components of VLDL-CH disappearance when compared with those of normal pigs. In normal pigs, feeding beef tallow resulted in longer half-lives of both components of VLDL-CH disappearance and no effect in pool size of both components of VLDL-CH disappearance than did feeding soy oil. In comparison, diabetic pigs fed beef tallow had a similar half-life of the primary component, a twofold shorter half-life of the secondary component, and threefold larger pool size of the primary component, and a similar pool size of the secondary component of VLDL-CH disappearance than did diabetic pigs fed soy oil. Thus, dietary fat seems to play an important role in regulation of glucose and VLDL-CH homeostasis in normal and diabetic animals.
Borzyszkowska, Joanna; Stanislawska-Sachadyn, Anna; Wirtwein, Marcin; Sobiczewski, Wojciech; Ciecwierz, Dariusz; Targonski, Radoslaw; Gruchala, Marcin; Rynkiewicz, Andrzej; Limon, Janusz
This study examines whether renin-angiotensin-aldosterone system gene polymorphisms: ACE (encoding for angiotensin converting enzyme) c.2306-117_404 I/D, AGTR1 (encoding for angiotensin II type-1 receptor) c.1080*86A>C and CYP11B2 (encoding for aldosterone synthase) c.-344C>T are associated with the extension of coronary atherosclerosis in a group of 647 patients who underwent elective coronary angiography. The extension of CAD was evaluated using the Gensini score. The polymorphisms were determined by PCR and RFLP assays. The associations between genotypes and the extent of coronary atherosclerosis were tested by the Kruskal-Wallis test, followed by pairwise comparisons using Wilcoxon test. The population has been divided into groups defined by: sex, smoking habit, past myocardial infarction, BMI (>, ≤ 25), age (>, ≤ 55), diabetes mellitus, level of total cholesterol (>, ≤ 200 mg/dl), LDL cholesterol (>, ≤ 130 mg/dl), HDL cholesterol (>, ≤ 40 mg/dl), triglycerides (>, ≤ 150 mg/dl). Significant associations between the ACE c.2306-117_404 I/D polymorphism and the Gensini score in men with high total cholesterol levels (P(Kruskal-Wallis) = 0.008; P(adjusted) = 0.009), high level of LDL cholesterol (P(Kruskal-Wallis) = 0.016; P(adjusted) = 0.028) and low level of HDL cholesterol (P(Kruskal-Wallis) = 0.04; P(adjusted) = 0.055) have been found. No association between the AGTR1 c.1080*86A>C and CYP11B2 c.-344C>T and the Gensini score has been found. These results suggest that men who carry ACE c.2306-117_404 DD genotype and have high total cholesterol, high LDL cholesterol and low HDL cholesterol levels may be predisposed to the development of more severe CAD.
Singh, Surendra Pratap; Mehla, Ram Kumar; Singh, Mahendra
Ten dry and pregnant Murrah buffaloes were selected to investigate the effect of Asparagus racemosus feeding on hormones, metabolites, milk yield, and plasma cholesterol levels. The treatment groups of buffaloes were fed with A. racemosus (shatavari) @ 150 g/day/animal during prepartum and @ 300 g/day/animal during the postpartum period. Blood samples collected on -6, -4, -2-week, day of parturition (0), and +2, +4, and +6-week postpartum were analyzed for plasma total cholesterol, triglycerides, HDL, low-density lipoproteins (LDL), prolactin, cortisol, and blood metabolites. Milk samples collected at weekly intervals (+1, +3, +5, and 7 weeks) were analyzed for total milk fat cholesterol. Prepartum plasma cholesterol concentrations were significantly higher in treatment group over the control (P < 0.05). Mean plasma triglycerides, LDL cholesterol, HDL cholesterol, glucose, and nonesterified fatty acid (NEFA) levels varied nonsignificantly between groups. Plasma prolactin and cortisol concentrations were significantly (P < 0.01) more in treatment group than in control group. On day of parturition, plasma prolactin, cortisol, LDL, and plasma total cholesterol were higher (P < 0.01) in treatment group buffaloes in comparison to control group. A. racemosus feeding significantly (P < 0.01) increased plasma prolactin, cortisol (P < 0.01), and milk fat cholesterol (P < 0.05) without affecting total cholesterol, HDL, LDL, glucose, and NEFA concentrations. The buffaloes of treatment group produced more milk (@ 0.526 kg/animal/day) suggesting thereby that A. racemosus is galactopoietic. It was concluded that feeding of A. racemosus increases plasma prolactin and cortisol and decreased plasma total cholesterol and LDL concentration.
Squillace, Nicola; Galli, Laura; Bandera, Alessandra; Castagna, Antonella; Madeddu, Giordano; Caramello, Pietro; Antinori, Andrea; Cattelan, Annamaria; Maggiolo, Franco; Cingolani, Antonella; Gori, Andrea; Monforte, Antonella d’Arminio
Abstract Investigation of the relationship between high-density lipoprotein-cholesterol (HDL-c) and the risk of developing cancer in a prospective cohort of human immunodeficiency virus (HIV)-infected patients. The Italian Cohort of Antiretroviral-naïve Patients Foundation Cohort is an Italian multicenter observational study recruiting HIV-positive patients while still antiretroviral treatment-naïve, regardless of the reason since 1997. Patients with at least 1 HDL-c value per year since enrollment and one such value before antiretroviral treatment initiation were included. HDL-c values were categorized as either low (<39 mg/dL in males or <49 mg/dL in females) or normal. Cancer diagnoses were classified as AIDS-defining malignancies (ADMs) or non-AIDS-defining malignancies (NADMs). Kaplan–Meier curves and Cox proportional-hazards regression models were used. Among 4897 patients (13,440 person-years of follow-up [PYFU]), 104 diagnoses of cancer were observed (56 ADMs, 48 NADMs) for an overall incidence rate of 7.7 (95% confidence interval [CI] 6.3–9.2) per 1000 PYFU. Low HDL-c values at enrollment were associated with higher risk both of cancer (crude hazard ratio [HR] 1.72, 95% CI 1.16–2.56, P = 0.007) and of NADM (crude HR 2.50, 95% CI 1.35–4.76, P = 0.003). Multivariate analysis showed that the risk of cancer diagnosis was higher in patients with low HDL-c values (adjusted HR [AHR] 1.87, 95% CI 1.18–2.95, P = 0.007) in older patients, those patients more recently enrolled, and in those with low current cluster of differentiation 4+ levels, and/or high current HIV-ribonucleic acid. The multivariate model confirmed an association between HDL-c (AHR 2.61, 95% CI 1.40–4.89, P = 0.003) and risk of NADM. Low HDL-c is an independent predictor of cancer in HIV-1-infected subjects. PMID:27603338
Eriksen, Kirsten T; Raaschou-Nielsen, Ole; McLaughlin, Joseph K; Lipworth, Loren; Tjønneland, Anne; Overvad, Kim; Sørensen, Mette
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of consumer products and have been detected worldwide in human blood. Recent studies mainly of highly exposed populations have indicated that PFOA and PFOS may affect serum cholesterol levels, but the magnitude of the effect may be inconsistent across exposure levels. The aim of the present cross-sectional study was to investigate the association between plasma PFOA and PFOS and total cholesterol in a general, middle-aged Danish population. The study population comprised 753 individuals (663 men and 90 women), 50-65 years of age, nested within a Danish cohort of 57,053 participants. Blood samples were taken from all cohort members at enrolment (1993-1997) and stored in a biobank at -150°C. Plasma levels of PFOA and PFOS and serum levels of total cholesterol were measured. The associations between plasma PFOA and PFOS levels and total cholesterol levels were analysed by generalized linear models, both crude and adjusted for potential confounders. We observed statistically significant positive associations between both perfluorinated compounds and total cholesterol, e.g. a 4.4 [95% CI = 1.1-7.8] higher concentration of total cholesterol (mg/dL) per interquartile range of PFOA plasma level. Sex and prevalent diabetes appeared to modify the association between PFOA and PFOS, respectively, and cholesterol. In conclusion, this study indicated positive associations between plasma PFOA and PFOS levels and total cholesterol in a middle-aged Danish population, although whether the observed pattern of results reflects a causal association is unclear.
Tandon, R S; Chandra, S
Serum cholesterol levels of six species of fresh water fishes were lowered due to trypanosome infection. The percentage of infection in the different species of hosts ranged from 3.27% in Clarias batrachus to 16.66% in Wallago attu. Loss in serum cholesterol level was highest (42.39%) in the spiny eel Mastocembelus armotus and lowest in the carp Cirrhina mrigala (4.56%). Thus hypocholesterolemia was evidently caused in the fishes by trypanosomes.
Eriksen, Kirsten T.; Raaschou-Nielsen, Ole; McLaughlin, Joseph K.; Lipworth, Loren; Tjønneland, Anne; Overvad, Kim; Sørensen, Mette
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of consumer products and have been detected worldwide in human blood. Recent studies mainly of highly exposed populations have indicated that PFOA and PFOS may affect serum cholesterol levels, but the magnitude of the effect may be inconsistent across exposure levels. The aim of the present cross-sectional study was to investigate the association between plasma PFOA and PFOS and total cholesterol in a general, middle-aged Danish population. The study population comprised 753 individuals (663 men and 90 women), 50–65 years of age, nested within a Danish cohort of 57,053 participants. Blood samples were taken from all cohort members at enrolment (1993–1997) and stored in a biobank at -150°C. Plasma levels of PFOA and PFOS and serum levels of total cholesterol were measured. The associations between plasma PFOA and PFOS levels and total cholesterol levels were analysed by generalized linear models, both crude and adjusted for potential confounders. We observed statistically significant positive associations between both perfluorinated compounds and total cholesterol, e.g. a 4.4 [95% CI = 1.1–7.8] higher concentration of total cholesterol (mg/dL) per interquartile range of PFOA plasma level. Sex and prevalent diabetes appeared to modify the association between PFOA and PFOS, respectively, and cholesterol. In conclusion, this study indicated positive associations between plasma PFOA and PFOS levels and total cholesterol in a middle-aged Danish population, although whether the observed pattern of results reflects a causal association is unclear. PMID:23441227
Kojima, Misaki; Ashino, Takashi; Yoshida, Takemi; Iwakura, Yoichiro; Sekimoto, Masashi; Degawa, Masakuni
We examined the role of hepatic interleukin (IL)-1alpha/beta in serum total cholesterol homeostasis using male and female IL-1-knockout (KO) mice and wild-type (WT) mice. Serum total cholesterol level was higher in males than in females in WT and KO mice. The difference between sexes was closely correlated with the difference in gene expression level of cholesterol 7alpha-hydroxylase (Cyp7a1), a rate-limiting enzyme for bile acid synthesis. No significant sex difference in gene expression level of 3-hydroxy-3-methylglutaryl-CoA reductase, a rate-limiting enzyme for cholesterol synthesis, was observed in WT mice. Interestingly, the gene expression level of hepatic Cyp7a1 was lower in KO mice than in sex-matched WT mice, while the serum total cholesterol level was the opposite. The present findings demonstrate that IL-1alpha and IL-1beta are positive regulators for the Cyp7a1 gene in steady-state mice and that Cyp7a1 is one of the factors that mediate the difference in serum total cholesterol level between sexes.
Bays, Harold E
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of β-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy. PMID:25045281
Bays, Harold E
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of β-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy.
Yamada, M; Wong, F L; Kodama, K; Sasaki, H; Shimaoka, K; Yamakido, M
The 28-year follow-up of a Japanese cohort, having collected vast amounts of data collected on total serum cholesterol (TC), provided an exceptional opportunity to examine TC temporal trends. The longitudinal statistical method of growth-curve analysis was used to elucidate the age-related changes in TC levels and to characterize these trends in relation to sex, birth cohort, time period, place of residence, and body mass index (BMI). Japanese TC levels at initial examination were remarkably lower than those in western countries. During the study period from 1958 to 1986, TC levels increased dramatically with age in both sexes. The slope of the cholesterol growth curve was steeper for women than for men, with the difference growing larger after age 40 years. Drastic changes in Japanese behavior and lifestyle, especially westernization of the diet, are thought to have affected the TC values as time-period effects. As a result of this temporal change, which affected different cohorts at different ages, TC values were higher in members of the younger cohort. The increase of the TC values as time-period effects were larger in earlier period than in later period. These time-period effects appeared to be almost similar in men and women. The TC growth curves also varied by city of residence. Subjects in urban areas had higher TC values than subjects in rural areas. Changes associated with BMI from 1958 to 1986 were only partially responsible for the increased steepness of the TC growth curve.
Borrell-Pages, Maria; Carolina Romero, July; Badimon, Lina
Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.
Peng, Diane; Fong, Amy; Pelt, Amanda van
: Purpose: Red yeast rice (RYR) supplementation has become a popular alternative to statin therapy in treating hypercholesterolemia. This state-of-the-science review seeks to explore the most recent evidence on the effectiveness and safety of RYR supplementation in treating dyslipidemic adults. This review extends the time frame of a meta-analysis performed by Li and colleagues in 2014; specifically, we looked at the literature published between September 2013 and April 2016. We conducted a search of four electronic databases-PsycINFO, CINAHL, PubMed, and Scopus-using the terms red yeast rice and cholesterol. We excluded studies that included berberine or lovastatin. Fifteen articles met the inclusion criteria. Eleven articles reported on randomized controlled trials, one reported on an open-label pilot study, and one reported on an open-label clinical trial. Two articles were meta-analyses. The 13 studies involved a total of 1,246 participants, with an additional 7,467 participants reported in the two meta-analyses. Significant reductions in low-density lipoprotein cholesterol and total cholesterol levels with RYR supplementation were observed in all trials. There were no significant changes in liver and kidney function, and 10 studies noted no significant changes in creatine kinase levels. Although RYR appears to be a safe and effective lipid-lowering agent, there is insufficient evidence to support the recommendation of RYR supplementation to patients. Further research is needed, including long-term studies, studies that include participants with comorbidities and complex medical histories, and studies that take into account the variability of formulation and dosage of RYR in the marketplace.
Fadini, Gian Paolo; Iori, Elisabetta; Marescotti, Maria Cristina; Vigili de Kreutzenberg, Saula; Avogaro, Angelo
Type 2 diabetes (T2D) is characterized by low HDL cholesterol (HDL-C) and HDL dysfunction. We herein tested whether lowering HbA1c affects HDL-C and reverse cholesterol transport (RCT). Forty-two uncontrolled T2D patients initiating basal insulin were included. HbA1c, HDL-C and RCT were assessed at baseline and after 6 months. At baseline, HDL-C and RCT were directly correlated (r = 0.50; p < 0.001). After 6 months of insulin therapy, HbA1c dropped from 8.8 ± 0.16% to 7.1 ± 0.1%, while average HDL-C and RCT did not change. Follow-up HDL-C and RCT were still correlated (r = 0.31; p = 0.033) and ΔHDL-C correlated with ΔRCT (r = 0.32; p = 0.029). ΔHbA1c correlated with ΔHDL-C (r = 0.43, p = 0.001), but not with ΔRCT. In patients with ΔHbA1c above the median value (1.3%), HDL-C (but not RCT) increased significantly. In conclusion, glucose control correlates with increased HDL-C, but not with improved RCT. Thus, persistent HDL dysfunction despite improved HbA1c and HDL-C can contribute to residual cardiovascular risk in T2D. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Mason, R Preston; Jacob, Robert F; Shrivastava, Sandeep; Sherratt, Samuel C R; Chattopadhyay, Amitabha
Cholesterol crystalline domains characterize atherosclerotic membranes, altering vascular signaling and function. Omega-3 fatty acids reduce membrane lipid peroxidation and subsequent cholesterol domain formation. We evaluated non-peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane fluidity, bilayer width, and cholesterol domain formation in model membranes. In membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha linolenic acid promoted the greatest reductions in cholesterol domains (by 65.5%, 54.9%, 46.8%, and 45.2%, respectively) compared to controls; other treatments had modest effects. EPA effects on cholesterol domain formation were dose-dependent. In membranes with 1:1 C/P (predisposing domain formation), DHA, but not EPA, dose-dependently increased membrane fluidity. DHA also induced cholesterol domain formation without affecting temperature-induced changes in-bilayer unit cell periodicity relative to controls (d-space; 57Å-55Å over 15-30°C). Together, these data suggest simultaneous formation of distinct cholesterol-rich ordered domains and cholesterol-poor disordered domains in the presence of DHA. By contrast, EPA had no effect on cholesterol domain formation and produced larger d-space values relative to controls (60Å-57Å; p<0.05) over the same temperature range, suggesting a more uniform maintenance of lipid dynamics despite the presence of cholesterol. These data indicate that EPA and DHA had different effects on membrane bilayer width, membrane fluidity, and cholesterol crystalline domain formation; suggesting omega-3 fatty acids with differing chain length or unsaturation may differentially influence membrane lipid dynamics and structural organization as a result of distinct phospholipid/sterol interactions. Copyright © 2016. Published
Cordova, C; Alessandri, C; Basili, S; Peverini, F; Ferro, D; Barsi, R; Paradiso, M
A case of a 45 years old man with an atherosclerotic stenosis of right internal carotid and TIA event is reported. The patient showed an increase of total cholesterol and LDL-cholesterol serum levels and, in particular, a very low familiar HDL2-cholesterol serum value. The possibility that this last condition could represent an important co-factor of the extracranial cerebrovascular disease is discussed. The usefulness of a long-term follow-up of all family members, showing the same lipids pattern, is also suggested.
Zhang, Xuyang; Wang, Kai
We performed a bivariate analysis on cholesterol and triglyceride levels on data from the Framingham Heart Study using a new score statistic developed for the detection of potential pleiotropic, or cluster, genes. Univariate score statistics were also computed for each trait. At a significance level 0.001, linkage signals were found at markers GATA48B01 on chromosome 1, GATA21C12 on chromosome 8, and ATA55A11 on chromosome 16 using the bivariate analysis. At the same significance level, linkage signals were found at markers 036yb8 on chromosome 3 and GATA3F02 on chromosome 12 using the univariate analysis. A strong linkage signal was also found at marker GATA112F07 by both the bivariate analysis and the univariate analysis, a marker for which evidence for linkage had been reported previously in a related study. PMID:14975130
Reimer, H L; Elford, R W; Shumak, S
To assess accuracy of blood cholesterol measurements in the office, fingerprick blood cholesterol assays by a dry reagent chemistry analyzer were compared in 151 patients with simultaneous venipuncture cholesterol assays by standard laboratory methods. Compared with the laboratory assay, seven of eight analyzers had total absolute biases less than 5%. Variability in results was comparable to that of community laboratories.
Ito, Sanae; Uenishi, Kazuhiro; Ishida, Hiromi; Uemura, Yukari; Kodama, Momoko; Fukuoka, Hideoki
Poor growth in utero has been suggested to be associated with adverse levels of serum cholesterol concentrations in later life. In Asia, there have only been a limited number of studies examining the relationship between fetal status and serum lipids, especially in adolescents. The objective of this study was to examine the relationships between birth weight and serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels; adjusting for current physical status including percent body fat, physical activity and nutrient intake in healthy Japanese late adolescents. The data of 573 late adolescents with an average age of 17.6 (287 boys and 286 girls) who underwent physical examinations which included blood sampling and who had all the required data, were analyzed. Birth weight was obtained from their maternal and child health handbook. Multiple regression analysis showed that birth weight was positively associated with serum HDL in girls, independently of percent body fat or fat intake, when adjusted for current body height and weight. There were no associations between birth weight and serum HDL in boys, or serum LDL in either sex.
Okumura, Kenji; Tsukamoto, Hideto; Tsuboi, Hideyuki; Hirayama, Haruo; Kamiya, Haruo; Watarai, Masato; Ishiki, Ryoji; Murohara, Toyoaki
This study is a prospective multicenter study designed to investigate the effects of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients with coronary heart disease, and to determine which factor is more closely associated with plaque regression. Participants (n = 63) were treated with pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was measured by ultrasound before and after treatment. Mean IMT slightly but significantly decreased (from 0.99 ± 0.33 to 0.94 ± 0.28 mm for overall, P = 0.01) regardless of the presence of pretreatment with other statins. There were no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases in mean IMT were observed significantly more frequently in subjects with high on-treatment HDL cholesterol levels than with low HDL cholesterol levels (P = 0.017). The change in mean IMT tended to be inversely correlated with increments in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often observed in the absence of diabetes and metabolic syndrome. In conclusion, we demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque. This effect was associated with the level of HDL cholesterol, and was stronger in the absence of diabetes and metabolic syndrome in our ischemic heart disease patients.
Ito, Yukihiko; Nakashima, Yuri; Matsuoka, Sayuri
People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.
Misra, Santosh K.; Biswas, Joydeep; Kondaiah, Paturu; Bhattacharya, Santanu
Background Six new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)n- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media. Methodology/Principal Findings To understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features. Conclusions/Significance -OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies. PMID:23861884
Fraunberger, P; Pilz, G; Cremer, P; Werdan, K; Walli, A K
Recent studies suggest that release of cytokines during inflammatory states such as septic shock leads to hypocholesterolemia. To examine whether tumor necrosis factor alpha (TNF), which is the major cytokine in inflammatory disease, causes hypocholesterolemia, we measured serum levels of total (bioactive and receptor-bound) TNF, cholesterol, Apo B, and Apo A1 in seven patients with septic shock over a period of 8 days. Since elevated serum TNF levels are accompanied by the release of soluble TNF receptors, levels of TNF receptors p55 and p75 were also measured. Patients with septic shock had significantly higher serum TNF and TNF receptor levels compared with healthy controls. Increased cytokine levels were accompanied by a significant decline in total serum cholesterol apolipoprotein A1 and B. In vitro studies with cultured human skin fibroblasts, human umbilical vein endothelial cells, and HepG2 hepatoma cells showed that TNF increased the degradation of 125I-labeled low-density lipoprotein in all the cell lines tested. Recombinant soluble TNF receptors inhibited the TNF-induced stimulation of low-density lipoprotein receptor in a concentration-dependent manner. However, the calculated ratio of TNF receptors to total TNF measured in serum of these patients was not able to counteract the stimulatory effect of TNF, possibly due to the higher molar excess of TNF receptors required to achieve this effect in vitro. Our data strengthen the hypothesis that serum values of total TNF determine the extent of hypocholesterolemia during sepsis and septic shock despite the presence of a high concentration of TNF receptors. Studies with recombinant TNF also confirm the role of TNF in hypocholesterolemia in inflammation.
Castillo, M; Amalik, F; Linares, A; García-Peregrín, E
The value of fish oil for prevention and/or treatment of human atherosclerosis has not been fully established. This study shows that replacement of saturated fat in young chick diet with menhaden oil produced a significant reversion of the hypercholesterolemia previously induced by coconut oil feeding. Fish oil also produced a clear decrease of plasma triacylglycerol levels. Coconut oil increased the percentages of 12:0 and 14:0 fatty acids, while menhaden oil increased those of 20:5 n-3 and 22:6 n-3. Percentages of 20:4 n-6, 18:2 n-6 and 18:1 n-9 significantly decreased by fish oil addition to the diet. Total cholesterol, phospholipid and protein contents of high and low density lipoproteins increased by coconut oil feeding. When coconut oil was replaced by menhaden oil, total cholesterol was significantly reduced in high, low and very low density lipoproteins. All chemical components of VLDL were decreased by menhaden oil feeding. Our results show a strong hypocholesterolemic effect of menhaden oil when this fat was supplemented to hypercholesterolemic chicks. The clear decrease found in arachidonic acid content of chick plasma and lipoproteins may contribute to the beneficial effects of fish oil consumption by lowering the production of its derived eicosanoids.
Barona, Jacqueline; Fernandez, Maria Luz
The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolism resulting from excess consumption of cholesterol. Dietary cholesterol has been shown to increase both LDL and HDL in those individuals who respond to a cholesterol challenge without altering the LDL cholesterol/HDL cholesterol ratio, a key marker of CVD risk. Further, dietary cholesterol has been shown to increase only HDL with no changes in LDL with average cholesterol consumption and during weight loss interventions. Ingestion of cholesterol has also been shown to increase the size of both LDL and HDL particles with the associated implications of a less atherogenic LDL particle as well as more functional HDL in reverse cholesterol transport. Other changes observed in lipoprotein metabolism are a greater number of large LDL and decreases in small LDL subfractions. All this information put together points to specific roles of dietary cholesterol in substantially altering intravascular processing of lipoproteins as well as reverse cholesterol transport.
Barona, Jacqueline; Fernandez, Maria Luz
The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolism resulting from excess consumption of cholesterol. Dietary cholesterol has been shown to increase both LDL and HDL in those individuals who respond to a cholesterol challenge without altering the LDL cholesterol/HDL cholesterol ratio, a key marker of CVD risk. Further, dietary cholesterol has been shown to increase only HDL with no changes in LDL with average cholesterol consumption and during weight loss interventions. Ingestion of cholesterol has also been shown to increase the size of both LDL and HDL particles with the associated implications of a less atherogenic LDL particle as well as more functional HDL in reverse cholesterol transport. Other changes observed in lipoprotein metabolism are a greater number of large LDL and decreases in small LDL subfractions. All this information put together points to specific roles of dietary cholesterol in substantially altering intravascular processing of lipoproteins as well as reverse cholesterol transport. PMID:23016129
Sun, Dan-Qin; Wu, Sheng-Jie; Liu, Wen-Yue; Wang, Li-Ren; Chen, Yi-Ran; Zhang, Dong-Chu; Braddock, Martin; Shi, Ke-Qing; Song, Dan
Objectives The relationship between normal low-density lipoprotein cholesterol (LDL-c) levels and non-alcoholic fatty liver disease (NAFLD) in non-obese individuals remains unclear. We aimed to investigate the precise prevalence and incidence of NAFLD within the normal LDL-c range in non-obese individuals. Design Cross-sectional and longitudinal study. Setting Wenzhou Medical Center of Wenzhou People's Hospital from 2010 to 2014. Participants 183 903 non-obese individuals were enrolled from a cross-sectional population, and a total of 16 173 initially NAFLD-free non-obese individuals were included who completed a 5-year follow-up examination in the longitudinal population. Results In our study, NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. The cross-sectional study showed that at baseline, the prevalence of NAFLD was 13.9% in non-obese individuals with normal LDL-c levels. The prospective study demonstrated that NAFLD-free participants developed NAFLD during the 5-year follow-up period, with a cumulative incidence of 14.4%. In addition, the ORs for NAFLD in the cross-sectional population were 1.11 (95% CI 1.04 to 1.18), 1.37 (95% CI 1.27 to 1.47) and 1.56 (95% CI 1.43 to 1.69), respectively, after adjusting for known confounding variables. The HRs for NAFLD in the longitudinal population were 1.15 (95% CI 0.98 to 1.36), 1.32 (95% CI 1.10 to 1.58) and 1.82 (95% CI 1.47 to 2.52), compared with Q1. Individuals with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD in non-obese individuals. Conclusions NAFLD is prevalent in the non-obese Chinese population. Furthermore, this is the first study to demonstrate that increased normal LDL-c levels are independently associated with an elevated risk of NAFLD in non-obese individuals. PMID:27927668
Hirowatari, Yuji; Manita, Daisuke; Kamachi, Keiko; Tanaka, Akira
Background Dietary habits are associated with obesity which is a risk factor for coronary heart disease. The objective is to estimate the change of lipoprotein(a) and other lipoprotein classes by calorie restriction with obesity index and Framingham risk score. Methods Sixty females (56 ± 9 years) were recruited. Their caloric intakes were reduced during the six-month period, and the calorie from fat was not more than 30%. Lipoprotein profiles were estimated at baseline and after the six-month period of calorie restriction. Cholesterol levels in six lipoprotein classes (HDL, LDL, IDL, VLDL, chylomicron and lipoprotein(a)) were analysed by anion-exchange liquid chromatography. The other tests were analysed by general methods. Additionally, Framingham risk score for predicting 10-year coronary heart disease risk was calculated. Results Body mass index, waist circumference, insulin resistance, Framingham risk score, total cholesterol, LDL-cholesterol and IDL-cholesterol were significantly decreased by the calorie restriction, and the protein and cholesterol levels of lipoprotein(a) were significantly increased. The change of body mass index was significantly correlated with those of TC, VLDL-cholesterol and chylomicron-cholesterol, and that of waist circumference was significantly correlated with that of chylomicron-cholesterol. The change of Framingham risk score was significantly correlated with the change of IDL-C. Conclusion Obesity indexes and Framingham risk score were reduced by the dietary modification. Lipoprotein profile was improved with the reduction of obesity indexes, but lipoprotein(a) was increased. The changes of obesity indexes and Framingham risk score were related with those of triglyceride-rich lipoproteins, e.g. IDL, VLDL and CM.
Alagwu, E A; Okwara, J E; Nneli, R O; Osim, E E
The beneficial effect of honey has been widely reported particularly in the treatment of wounds and gastrointestinal tract disorders. However there is paucity of reports on its effect on the plasma high density lipoproteins (HDL), very low density lipoproteins (VLDL), low density lipoproteins (LDL) and triglycerides (TG) including cholesterol levels despite common consumption of honey worldwide including, Nigeria. The effect of the widely consumed unrefined Nigeria honey on plasma HDL, VLDL, LDL, TG, cholesterol and cardiovascular risk predictive index (CVPI) was studied using 20 adult male albino rats to ascertain its scientific and clinical relevance. The rats were randomly assigned into 2 groups, the control and honey-fed (test) groups, ten in each group. The rats weighed between 190-200gm at the start of the study. The control group was fed on normal rat (Pfizer-Nigeria) while the test group was fed on normal rat feed and honey (1ml of honey was added to 10ml of drinking water given once every day) for 22 weeks. At the end of the experiment, the rats were anesthetized with thiopentone sodium and blood collected by cardiac puncture. Serum TG, HDL, VLDL, LDL and total cholesterol in the control and the test groups were determined. The results showed significant increase in the level of plasma TG, HDL, and VLDL in the test group when compared with the control group. In contrast, there were significant decreases in the levels of plasma LDL and total cholesterol in the test when compared with the control group. Computed values of CVPI showed significant increase in the test values compared to that of the control. It is concluded that consumption of unrefined Nigeria honey significantly improved lipid profile and computed cardiovascular disease predictive index in male albino rats.
Broitman, S A; Cerda, S; Wilkinson, J
While epidemiologic and concordant experimental data indicate a direct relationship between dietary fat (and presumably caloric) intake and the development of colon cancer, the effect of dietary cholesterol on this disease is still not clear. However, there appears to be a developing literature concerning an inverse relationship between serum and plasma cholesterol levels, and the risk for colon cancer. Findings that low serum cholesterol levels are apparent as early as ten years prior to the detection of colon cancer implies that sub clinical disease is probably not involved initially in this process. The possibility of low serum cholesterol as a bio-marker was considered in epidemiologic studies which focused upon obese men with lower than normal serum cholesterol levels who were found to be at increased risk to colon cancer. While the relationship between low serum cholesterol and colonic or intestinal cholesterol metabolism is presently not understood, current genetic studies provide a promising though as yet unexplored potential association. Alterations which occur during the developmental progression of colonic cancer include changes in chromosome 5, which also carries two genes vital to the biosynthesis and regulation of systemic and cellular cholesterol metabolism, 3-hydroxy-3-methylglutaryl coenzyme A synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA R). Regulation of cholesterol metabolism in intestinal cells in vivo and in vitro varies from that seen in normal fibroblasts or hepatocytes in terms of exogenous sources of cholesterol and how these sources regulate internal synthesis. Colonic cancer cells have been used to assess small bowel enterocyte cholesterol metabolism, which has been possible because of their ability to differentiate in culture, however information regarding true colonic enterocyte cholesterol metabolism is relatively scarce. Colonic cancer cells have been shown to possess a diminished or nonexistent ability to use
Ferns, G A; Robinson, D; Stocks, J; Bevan, E; Williams, P; Galton, D J
The relationship between plasma HDL-cholesterol subfractions (HDL2 and HDL3), measured using a differential precipitation method, and serum triglycerides, was studied in 402 healthy Caucasian males attending a health screening centre in London. Mean values for HDL2 and HDL3 were 0.42 +/- 0.24 mmol/L and 0.81 +/- 0.15 mmol/L respectively. HDL2 was found to show a stronger negative correlation with serum triglyceride and a stronger positive correlation with total HDL than HDL3. HDL2 also showed a stronger correlation with age than either total HDL or HDL3. Mean levels of HDL2 were 20% higher in subjects over 55 years of age compared with those who were less than 55 years of age. Reference values of HDL2 and HDL3 are presented for different age ranges.
Khajuria, Ravi K; Bhardwaj, Vikram; Gupta, Rajinder K; Sharma, Preeti; Somal, Priti; Mehta, Pradeep; Qazi, Ghulam N
This paper describes the development of a normal-phase liquid chromatograph-UV-diode array detection-positive ion atmospheric pressure chemical ionization-mass spectrometry method for the simultaneous identification and quantitation of cholesterol, androst-4-ene-3,17-dione (AD), and androsta-1,4-diene-3,17-dione (ADD) in fermentation broths. The compounds detected under positive ion atmospheric pressure chemical ionization on a mass spectrometer by selected ion monitoring are separated by normal-phase high-performance liquid chromatography. [M+H]+ ions are taken into consideration for quantitation of AD and ADD, and [M-H2O+H]+ ions are considered for quantitation of cholesterol. The compounds are analyzed on a Si60 silica (5 microm, 125 x 4-mm i.d.) Merck column using a 2:3 isocratic mixture of isopropyl alcohol and hexane. The calibration curves resulting from the reference compounds in the concentration range of 100-5000 pg on column exhibit a good linear correlation (r2 > or = 0.996). The method is validated by analyzing six replicates of broth samples fortified with three compounds, namely, cholesterol, AD, and ADD, at 0.050 and 0.5 microg/g levels. The mean recoveries for the fortifications range from 90% to 98% with relative standard deviations in the range of 3.36% to 9.78%. The method is developed to study the qualitative as well as quantitative conversion of cholesterol to AD and ADD by a microorganism identified as Nocardia sp. These studies helped the investigation of the reaction kinetics, which showed that the molar biotransformation of cholesterol into AD and ADD was 21%, even when the reaction was prolonged for 96 h.
Zamrazilová, H; Hainer, V; Sedlácková, D; Papezová, H; Kunesová, M; Bellisle, F; Hill, M; Nedvídková, J
Obestatin is a recently discovered peptide produced in the stomach, which was originally described to suppress food intake and decrease body weight in experimental animals. We investigated fasting plasma obestatin levels in normal weight, obese and anorectic women and associations of plasma obestatin levels with anthropometric and hormonal parameters. Hormonal (obestatin, ghrelin, leptin, insulin) and anthropometric parameters and body composition were examined in 15 normal weight, 21 obese and 15 anorectic women. Fasting obestatin levels were significantly lower in obese than in normal weight and anorectic women, whereas ghrelin to obestatin ratio was increased in anorectic women. Compared to leptin, only minor differences in plasma obestatin levels were observed in women who greatly differed in the amount of fat stores. However, a negative correlation of fasting obestatin level with body fat indexes might suggest a certain role of obestatin in the regulation of energy homeostasis. A significant relationship between plasma obestatin and ghrelin levels, independent of anthropometric parameters, supports simultaneous secretion of both hormones from the common precursor. Lower plasma obestatin levels in obese women compared to normal weight and anorectic women as well as increased ghrelin to obestatin ratio in anorectic women might play a role in body weight regulation in these pathologies.
Poveda, Natalia E.; Garcés, María F.; Ruiz-Linares, Carlos E.; Varón, Diana; Valderrama, Sergio; Sanchez, Elizabeth; Castiblanco-Cortes, Adriana; Agudelo-Zapata, Yessica; Sandoval-Alzate, Héctor Fabio; Leal, Luis G.; Ángel-Müller, Edith; Ruíz-Parra, Ariel I.; González-Clavijo, Angélica M.; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E.
Adipsin is a protease produced at high levels by adipose tissue. It is involved in complement activation and metabolic control. The objective of this study was to determine the changes in adipsin levels during different stages of normal pregnancy, and its association with obstetric outcomes, such as preeclampsia. This nested case-control study in a longitudinal cohort included normal pregnant (n = 54) and preeclamptic (n = 18) women, both followed throughout pregnancy. Additionally, some of the normal pregnant women were followed up three months postpartum (n = 18). Healthy non-pregnant women were also studied during their menstrual cycle (n = 20). The results of this study show that in healthy non-pregnant women, adipsin levels did not change significantly during the menstrual cycle. In normal pregnant women, adipsin levels were lower (p < 0.01) when compared with non-pregnant healthy women, but these serum levels increased again during postpartum (p < 0.001). Adipsin levels were significantly elevated in preeclamptic women in late pregnancy (P < 0.01). A significant correlation was not found between leptin and adipsin during the three periods of gestation studied in healthy pregnant and preeclamptic women. Our results suggest that adipsin may be involved in pregnancy-associated metabolic changes. Moreover, the increase of adipsin levels towards late gestation in preeclamptic women could be related to the pathophysiology of this disease. PMID:26832661
over a 40 day period for HDtJICholesteroll and Total Choleis- added with the "reverse" technique, This technique is only poai- tarot . The results are...Stand- tarot and Total Cholestero levels, it is beat that eet laoatr ard and a control Serum were each analyzed 10 times giving the * determinle its
Snel, M; Sleddering, M A; Pijl, H; Nieuwenhuizen, W F; Frölich, M; Havekes, L M; Romijn, J A; Jazet, I M
Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity. To study the effect of dietary supplementation with PS on cholesterol and glucose metabolism in humans. Twelve men with the metabolic syndrome (MetS) (according to the International Diabetes Federation (IDF) criteria; age 51+/-2 years (mean+/-s.e.m.); body mass index (BMI) 32+/-1 kg/m(2)) were randomly assigned to 4 weeks of PS (500 mg twice daily) and 4 weeks of placebo (P) in a double-blind cross-over study, with a 4-week wash-out period between both interventions. At the end of each intervention anthropometric measures and serum lipids were measured and an intravenous glucose tolerance test (IVGTT) was performed. Phytosphingosine did not affect body weight and fat mass compared with P. PS decreased serum total cholesterol (5.1+/-0.3 (PS) vs 5.4+/-0.3 (P) mmol/l; P<0.05) and low-density lipoprotein (LDL)-cholesterol levels (3.1+/-0.3 (PS) vs 3.4+/-0.3 (P) mmol/l; P<0.05), whereas it did not alter serum triglyceride and high-density lipoprotein (HDL)-cholesterol levels. In addition, PS lowered fasting plasma glucose levels (6.2+/-0.3 (PS) vs 6.5+/-0.3 (P) mmol/l; P<0.05). PS increased the glucose disappearance rate (K-value) by 9.9% during the IVGTT (0.91+/-0.06 (PS) vs 0.82+/-0.05 (P) %/min; P<0.05) at similar insulin levels, compared with P, thus implying enhanced insulin sensitivity. PS induced only minor gastrointestinal side effects. Dietary supplementation of PS decreases plasma cholesterol levels and enhances insulin sensitivity in men with the MetS.
Schwartz, Joseph A; Rowland, Meghan W; Beaver, Kevin M
Low cholesterol levels have been found to be associated with a wide range of behavioral problems, including violent and criminal behavior, and a wide range of psychological problems including impulsivity, depression, and other internalizing problems. The casual mechanisms underlying these associations remain largely unknown, but genetic factors may play a role in the etiology of such associations as previous research has found significant genetic influence on cholesterol levels and various deleterious behavioral and psychological outcomes. The current study addressed this existing gap in the literature by performing a genetically sensitive test of the association between cholesterol levels and various outcomes including levels of self-control, depressive symptoms, anger expression, and neuroticism. DeFries-Fulker (DF) analysis was used to analyze data from 388 twin pairs nested within the Survey of Midlife Development in the United States (MIDUS). The results of the genetically informed models revealed that high-density lipoprotein (HDL) cholesterol levels were negatively and significantly associated with depressive symptoms, had a marginally significant effect on neuroticism, and a nonsignificant effect on both anger expression and self-control. The findings may not extrapolate to the larger population of American adults since the subsample of twins with cholesterol information may not be nationally representative. Genetic influences play a significant role in the association between cholesterol levels and various deleterious outcomes and failing to control for these influences may result in model misspecification and may increase the probability of detecting a significant association when one does not actually exist. Copyright © 2014 Elsevier B.V. All rights reserved.
Venkatanarayanan, S; Nagarajan, B
Total and lipoprotein cholesterol in serum have been determined in patients with leukemia and lymphoma. Untreated patients were hypocholesterolemic with reduced lipoprotein cholesterol content. On successful chemotherapy most of the patients showed near normal total cholesterol levels with a subsequent increase in LDL cholesterol content. A rapid, sensitive and inexpensive method is reported using agarose electrophoresis and quantitation of cholesterol by Liebermann-Burchard reaction.
Kumanyika, S K; Adams-Campbell, L; Van Horn, B; Ten Have, T R; Treu, J A; Askov, E; Williams, J; Achterberg, C; Zaghloul, S; Monsegu, D; Bright, M; Stoy, D B; Malone-Jackson, M; Mooney, D; Deiling, S; Caulfield, J
To evaluate a cardiovascular nutrition education package designed for African-American adults with a wide range of literacy skills. Comparison of a self-help group and a full-instruction group; each group received nutrition counseling and clinical monitoring every 4 months. Three hundred thirty African-American adults, aged 40 to 70 years, with elevated cholesterol level or high blood pressure were randomly assigned to the self-help or full-instruction group; 255 completed the 12-month follow-up. Counseling to reduce intake of dietary fat, cholesterol, and sodium was based on Cardiovascular Dietary Education System (CARDES) materials, which included food-picture cards, a nutrition guide (self-help and full-instruction group), a video and audiotape series, and 4 classes (full-instruction group only). Changes in lipid levels and blood pressure after 12 months. Primary analyses consisted of repeated-measures analysis of variance to examine effects of time and randomization group on outcomes. Total cholesterol and low-density lipoprotein cholesterol level decreased by 7% to 8% in the self-help and full-instruction groups of men and women (P < .01). The ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) decreased in both groups of women and in the men in the full-instruction group (P < .01). In full-instruction and self-help participants with elevated blood pressure at baseline, systolic blood pressure decreased by 7 to 11 mm Hg and diastolic blood pressure decreased by 4 to 7 mm Hg (P < .01). Outcomes did not differ by literacy scores but were positively related to the reported initial frequency of using CARDES materials. These results suggest that periodic nutrition counseling based on CARDES materials used for home study can enhance management of lipid levels and blood pressure in African-American outpatients.
Wandeler, G; Paccaud, F; Vollenweider, P; Waeber, G; Mooser, V; Bochud, M
Limited information is available on the quantitative relationship between family history and the corresponding underlying traits. We analyzed these associations for blood pressure, fasting blood glucose, and cholesterol levels. Data were obtained from 6,102 Caucasian participants (2,903 men and 3,199 women) aged 35-75 years using a population-based cross-sectional survey in Switzerland. Cardiovascular disease risk factors were measured, and the corresponding family history was self-reported using a structured questionnaire. The prevalence of a positive family history (in first-degree relatives) was 39.6% for hypertension, 22.3% for diabetes, and 29.0% for hypercholesterolemia. Family history was not known for at least one family member in 41.8% of participants for hypertension, 14.4% for diabetes, and 50.2% for hypercholesterolemia. A positive family history was strongly associated with higher levels of the corresponding trait, but not with the other traits. Participants who reported not to know their family history of hypertension had a higher systolic blood pressure than participants with a negative history. Sibling histories had higher positive predictive values than parental histories. The ability to discriminate, calibrate, and reclassify was best for the family history of hypertension. Family history of hypertension, diabetes, and hypercholesterolemia was strongly associated with the corresponding dichotomized and continuous phenotypes. Copyright 2009 S. Karger AG, Basel.
Khalil, Md. Ibrahim; Tanvir, E. M.; Sulaiman, Siti Amrah; Gan, Siew Hua
The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation. PMID:26064893
Khalil, Md Ibrahim; Tanvir, E M; Afroz, Rizwana; Sulaiman, Siti Amrah; Gan, Siew Hua
The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.
The relationship between breakfast habits and plasma total cholesterol (TC) levels was examined in a sample of 530 US schoolchildren ages 9-19. Based on response to a 124-item food checklist, subjects' usual breakfast habits were classified into one of six discrete categories: 1) Skipper, 2) Ready-to-Eat (RTE) cereal with Fiber, 3) Traditional Breakfast, 4) Chips or Sweets, 5) Other RTE, or 6) Mixed Breakfasts. Breakfast skippers, controlling for age, gender, and body mass index, had significantly (p less than 0.05) higher TC levels, 172 mg/dl, than breakfast consumers, 160 mg/dl. Among breakfast eaters, the mean TC of the "Fiber RTE" group was significantly lower (p less than 0.01) than all other breakfast consumers. Usual skippers were less likely to believe in the importance and benefits of breakfast as well as the need to eat foods high in fiber. These findings suggest that encouraging chronic breakfast skippers to modify their dietary habits may improve their nutritional status and possibly reduce their risk for future heart disease.
Chen, Yequn; Chen, Chang; Ke, Xiayi; Xiong, Longgen; Shi, Yongying; Li, Jiafu; Tan, Xuerui; Ye, Shu
Non-O type of ABO blood group has been associated with a predisposition to coronary heart disease. It is thought that this association is partly mediated by increased cholesterol levels in non-O-type individuals. In this study, we sought to estimate the mediation effect size. In a group of individuals (n=6476) undergoing coronary angiography, we detected associations of non-O type with significant coronary artery disease with >50% stenosis in ≥1 coronary arteries (odds ratio, 1.24; 95% confidence interval, 1.10-1.39; P=2.6×10(-4)) and with prevalent or incident myocardial infarction (odds ratio, 1.22; 95% confidence interval, 1.09-1.37; P=1.2×10(-3)). Subjects of non-O type had higher levels of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (mean [SEM] in mmol/L: 4.931[0.021], 3.041 [0.018], and 3.805 [0.020] in non-O type compared with 4.778 [0.026], 2.906 [0.021], and 3.669 [0.024] in O type; P=3.8×10(-7), P=1.5×10(-7), and P=3.1×10(-7), respectively). Mediation analyses indicated that 10% of the effect of non-O type on coronary artery disease susceptibility was mediated by increased low-density lipoprotein cholesterol level (P=7.8×10(-4)) and that 11% of the effect of non-O type on myocardial infarction risk was mediated by raised low-density lipoprotein cholesterol level (P=2.0×10(-3)). In a model in which it is presumed that cholesterol is a mediator of the associations of ABO group with coronary artery disease and myocardial infarction, around 10% of the effect of non-O type on coronary artery disease and myocardial infarction susceptibility was mediated by its influence on low-density lipoprotein cholesterol level.
Normal Nasal Gene Expression Levels Using cDNA Array Technology.
The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...
Normal Nasal Gene Expression Levels Using cDNA Array Technology.
The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...
Sáez, María E; Martínez-Larrad, María T; Ramírez-Lorca, Reposo; González-Sánchez, José L; Zabena, Carina; Martinez-Calatrava, María J; González, Alejandro; Morón, Francisco J; Ruiz, Agustín; Serrano-Ríos, Manuel
Background Genes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM) or cardiovascular diseases are not disease specific, since clinically related disorders also share genetic components. Cysteine protease Calpain 10 (CAPN10) has been associated with T2DM, hypertension, hypercholesterolemia, increased body mass index (BMI) and polycystic ovary syndrome (PCOS), a reproductive disorder of women in which isunlin resistance seems to play a pathogenic role. The calpain 5 gene (CAPN5) encodes a protein homologue of CAPN10. CAPN5 has been previously associated with PCOS by our group. In this new study, we have analysed the association of four CAPN5 gene variants(rs948976A>G, rs4945140G>A, rs2233546C>T and rs2233549G>A) with several cardiovascular risk factors related to metabolic syndrome in general population. Methods Anthropometric measurements, blood pressure, insulin, glucose and lipid profiles were determined in 606 individuals randomly chosen from a cross-sectional population-based epidemiological survey in the province of Segovia in Central Spain (Castille), recruited to investigate the prevalence of anthropometric and physiological parameters related to obesity and other components of the metabolic syndrome. Genotypes at the four polymorphic loci in CAPN5 gene were detected by polymerase chain reaction (PCR). Results Genotype association analysis was significant for BMI (p ≤ 0.041), diastolic blood pressure (p = 0.015) and HDL-cholesterol levels (p = 0.025). Different CAPN5 haplotypes were also associated with diastolic blood pressure (DBP) (0.0005 ≤ p ≤ 0.006) and total cholesterol levels (0.001 ≤ p ≤ 0.029). In addition, the AACA haplotype, over-represented in obese individuals, is also more frequent in individuals with metabolic syndrome defined by ATPIII criteria (p = 0.029). Conclusion As its homologue CAPN10, CAPN5 seems to influence traits related to increased risk for cardiovascular diseases. Our results also
Cesar, Thais B; Aptekmann, Nancy P; Araujo, Milena P; Vinagre, Carmen C; Maranhão, Raul C
Orange juice (OJ) is regularly consumed worldwide, but its effects on plasma lipids have rarely been explored. This study hypothesized that consumption of OJ concentrate would improve lipid levels and lipid metabolism, which are important in high-density lipoprotein (HDL) function in normolipidemic (NC) and hypercholesterolemic (HCH) subjects. Fourteen HCH and 31 NC adults consumed 750 mL/day OJ concentrate (1:6 OJ/water) for 60 days. Eight control subjects did not consume OJ for 60 days. Plasma was collected before and on the last day for biochemical analysis and an in vitro assay of transfers of radioactively labeled free-cholesterol, cholesteryl esters, phospholipids, and triglycerides from lipoprotein-like nanoemulsions to HDL. Orange juice consumption decreased low-density lipoprotein cholesterol (160 ± 17 to 141 ± 26 mg/dL, P < .01) in the HCH group but not in the NC group. HDL-cholesterol and triglycerides remained unchanged in both groups. Free-cholesterol transfer to HDL increased (HCH: 4.4 ± 2 to 5.6 ± 1%, NC: 3.2 ± 2 to 6.2 ± 1%, P< .05) whereas triglyceride (HCH 4.9 ± 1 to 3.1 ± 1%, NC 4.4 ± 1 to 3.4 ± 1%, P< .05) and phospholipid (HCH 21.6 ± 2 to 18.6 ± 3%, NC 20.2 ± 2 to 18.4 ± 2%, P < .05) transfers decreased in both groups. Cholesteryl-ester transfer decreased only in HCH (3.6 ± 1 to 3.1 ± 1%, P < .05), but not in NC. In control subjects, plasma lipids and transfers were unaltered for 60 days. Thus, by decreasing atherogenic low-density lipoprotein cholesterol in HCH and increasing HDL ability to take up free cholesterol in HCH and NC, OJ may be beneficial to both groups as free-cholesterol transfer to HDL is crucial for cholesterol esterification and reverse cholesterol transport.
Dávalos, Alberto; Fernández-Hernando, Carlos
There has been strong evolutionary pressure to ensure that an animal cell maintains levels of cholesterol within tight limits for normal function. Imbalances in cellular cholesterol levels are a major player in the development of different pathologies associated to dietary excess. Although epidemiological studies indicate that elevated levels of high-density lipoprotein (HDL)-cholesterol reduce the risk of cardiovascular disease, recent genetic evidence and pharmacological therapies to raise HDL levels do not support their beneficial effects. Cholesterol efflux as the first and probably the most important step in reverse cholesterol transport is an important biological process relevant to HDL function. Small non-coding RNAs (microRNAs), post-transcriptional control different aspects of cellular cholesterol homeostasis including cholesterol efflux. miRNA families miR-33, miR-758, miR-10b, miR-26 and miR-106b directly modulates cholesterol efflux by targeting the ATP-binding cassette transporter A1 (ABCA1). Pre-clinical studies with anti-miR therapies to inhibit some of these miRNAs have increased cellular cholesterol efflux, reverse cholesterol transport and reduce pathologies associated to dyslipidemia. Although miRNAs as therapy have benefits from existing antisense technology, different obstacles need to be solved before we incorporate such research into clinical care. Here we focus on the clinical potential of miRNAs as therapeutic target to increase cholesterol efflux and reverse cholesterol transport as a new alternative to ameliorate cholesterol-related pathologies.
Barn, Kulpreet; Laftavi, Mark; Pierce, Drew; Ying, Chin; Boden, William E; Pankewycz, Oleh
Long-term kidney transplant graft and patient survival is often limited by cardiovascular (CV) disease. Risk factors for CV disease such as diabetes, hypertension and elevated low-density lipoprotein levels are well documented; however, the impact of low levels of high-density lipoprotein (HDL) has not been defined. We performed a retrospective chart review of 324 consecutive renal transplant recipients from 2001 to 2007 to correlate baseline HDL levels with major adverse cardiovascular events (MACEs) defined as a composite of new onset CV illness, cerebral vascular events and peripheral vascular disease. A total of 92 MACEs occurred over a total of 1913 patient years of follow-up. Low HDL cholesterol levels were noted in 58.3% of patients. Compared with those with normal HDL levels, a greater percentage of patients with low HDL levels had post-transplant MACEs (20% vs. 60% respectively) and experienced an increased rate of all cause mortality. Sixty-two percent of all MACEs occurred in patients with low HDL levels. In the low HDL group, the odds ratio for experiencing a MACE was 1.92. Therefore, HDL cholesterol may provide an important new therapeutic target to prevent vascular morbidity and mortality following renal transplantation.
Extract of black tea (pu-ehr) inhibits postprandial rise in serum cholesterol in mice, and with long term use reduces serum cholesterol and low density lipoprotein levels and renal fat weight in rats.
Fujita, Hiroyuki; Yamagami, Tomohide
A water-soluble extract of a traditional Chinese fermented black tea, pu-ehr, decomposes bile acid cholesterol micelles. This black tea extract (BTE) was studied to see if it could decrease the postprandial elevation of blood cholesterol levels after a single administration in ddY mice. It was found that BTE (0.3 g/kg) significantly decreased the postprandial rise in blood cholesterol levels after oral administration of cholesterol (130 mg/kg). A non-fermented tea (i.e. green tea) extract did not prevent the postprandial increase in blood cholesterol. In a subsequent study, 5-week-old Sprague-Dawley (SD) rats were fed BTE for 3 weeks, following which a dose-dependent and significant decrease in serum total cholesterol levels (1.36 mmol/L, 0.1% BTE, p < 0.05) was found and also in renal fat weight (0.3% BTE, p < 0.05). LDL cholesterol levels (0.51 mmol/L, 0.1% BTE, p < 0.05) were also significantly decreased. There were no significant changes in the weights of other organs or in the serum levels of other clinical markers. Thus, BTE has a specific antihypercholesterol effect in rodents, which might potentially aid in the management of hyperlipidaemia in man.
Background Low plasma high-density lipoprotein cholesterol (HDL-C) levels are a strong, independent, but poorly understood risk factor for cardiovascular disease (CVD). Although this atherogenic lipid abnormality has been widely reported in Australia’s Indigenous peoples, Aboriginal and Torres Strait Islanders, the evidence has not come under systematic review. This review therefore examines published data for Indigenous Australians reporting 1) mean HDL-C levels for both sexes and 2) factors associated with low HDL-C. Methods PubMed, Medline and Informit ATSI Health databases were systematically searched between 1950 and 2012 for studies on Indigenous Australians reporting mean HDL-C levels in both sexes. Retrieved studies were evaluated by standard criteria. Low HDL-C was defined as: <1.0 mmol/L. Analyses of primary data associating measures of HDL-C with other CVD risk factors were also performed. Results Fifteen of 93 retrieved studies were identified for inclusion. These provided 58 mean HDL-C levels; 29 for each sex, most obtained in rural/regional (20%) or remote settings (60%) and including 51–1641 participants. For Australian Aborigines, mean HDL-C values ranged between 0.81-1.50 mmol/L in females and 0.76-1.60 mmol/L in males. Two of 15 studies reported HDL-C levels for Torres Strait Islander populations, mean HDL-C: 1.00 or 1.11 mmol/L for females and 1.01 or 1.13 mmol/L for males. Low HDL-C was observed only in rural/regional and remote settings - not in national or urban studies (n = 3) in either gender. Diabetes prevalence, mean/median waist-to-hip ratio and circulating C-reactive protein levels were negatively associated with HDL-C levels (all P < 0.05). Thirty-four per cent of studies reported lower mean HDL-C levels in females than in males. Conclusions Very low mean HDL-C levels are common in Australian Indigenous populations living in rural and remote communities. Inverse associations between HDL-C and central obesity, diabetes
Grosheva, Inna; Haka, Abigail S.; Qin, Chunbo; Pierini, Lynda M.; Maxfield, Frederick R.
Objective Interaction of macrophages with aggregated matrix-anchored lipoprotein deposits is an important initial step in atherogenesis. Aggregated lipoproteins require different cellular uptake processes than those used for endocytosis of monomeric lipoproteins. In this study, we tested the hypothesis that engagement of aggregated LDL (agLDL) by macrophages could lead to local increases in free cholesterol levels and that these increases in free cholesterol regulate signals that control cellular actin. Methods and Results AgLDL resides for prolonged periods in surface-connected compartments. While agLDL is still extracellular, we demonstrate that an increase in free cholesterol occurs at sites of contact between agLDL and cells due to hydrolysis of agLDL-derived cholesteryl ester. This increase in free cholesterol causes enhanced actin polymerization around the agLDL. Inhibition of cholesteryl ester hydrolysis results in decreased actin polymerization. Conclusions We describe a novel process that occurs during agLDL-macrophage interactions in which local release of free cholesterol causes local actin polymerization, promoting a pathologic positive feedback loop for increased catabolism of agLDL and eventual foam cell formation. PMID:19556523
Grosheva, Inna; Haka, Abigail S; Qin, Chunbo; Pierini, Lynda M; Maxfield, Frederick R
Interaction of macrophages with aggregated matrix-anchored lipoprotein deposits is an important initial step in atherogenesis. Aggregated lipoproteins require different cellular uptake processes than those used for endocytosis of monomeric lipoproteins. In this study, we tested the hypothesis that engagement of aggregated LDL (agLDL) by macrophages could lead to local increases in free cholesterol levels and that these increases in free cholesterol regulate signals that control cellular actin. AgLDL resides for prolonged periods in surface-connected compartments. Although agLDL is still extracellular, we demonstrate that an increase in free cholesterol occurs at sites of contact between agLDL and cells because of hydrolysis of agLDL-derived cholesteryl ester. This increase in free cholesterol causes enhanced actin polymerization around the agLDL. Inhibition of cholesteryl ester hydrolysis results in decreased actin polymerization. We describe a novel process that occurs during agLDL-macrophage interactions in which local release of free cholesterol causes local actin polymerization, promoting a pathological positive feedback loop for increased catabolism of agLDL and eventual foam cell formation.
Nath, Soumitra; Jahan, Wasima
The present study was carried out to determine the serum total cholesterol (TC) level in young adults of Dibrugarh town of Assam and to find the association of serum cholesterol level with body mass index (BMI) and waist-circumference (WC). A cross-sectional study was done among 150 healthy young adults aged 20-30 years. TC was estimated by the enzymatic method. Hypercholesterolemia was defined as TC > 200 mg/dl. Cases were classified into different categories of BMI and WC according to the recommendations of WHO/IASO/IOTF (2000). The range of TC level in the study group was found to be (146-212) mg/dl. Mean cholesterol level in males and females were 169.5±3.6 and 172.3±15.09 mg/dl respectively. 7% of the cases had hypercholesterolemia. TC was significantly correlated with BMI (r=0.90, p<0.001) and WC (r=0.73, p<0.001 in males and r=0.86, p<0.001 in females). We conclude that young adults ≥20 years of age and especially who are overweight should be advised routine cholesterol testing so that preventive measures can be adopted to avoid hypercholesterolemia and it's complications in future life.
Monteleone, Palmiero; Santonastaso, Paolo; Pannuto, Marilena; Favaro, Angela; Caregaro, Lorenza; Castaldo, Eloisa; Zanetti, Tatiana; Maj, Mario
Increased levels of cholesterol have been reported in patients with bulimia nervosa (BN), but all but one of the published studies were performed on non-fasting subjects, which limits the interpretation of this finding. Moreover, the relationships between serum lipids and comorbid psychiatric disorders or bulimic psychopathology have scarcely been investigated. We measured serum levels of total cholesterol, triglycerides, glucose, 17beta-estradiol and thyroid hormones in 75 bulimic women and 64 age-matched healthy females after an overnight fast. Compared with healthy women, bulimic patients exhibited significantly enhanced serum levels of cholesterol and triglycerides, but similar values of glucose, 17beta-estradiol, FT3 and FT4. No significant differences emerged in these variables between patients with or without comorbid depression, borderline personality disorder or lifetime anorexia nervosa. Circulating cholesterol was positively correlated to the patients' drive for thinness, ineffectiveness, enteroceptive awareness and impulse regulation sub-item scores of the Eating Disorder Inventory-2. These findings confirm that BN is associated with increased levels of serum lipids. This alteration may be involved in the pathophysiology of certain psychopathological characteristics of BN and cannot be explained by the co-occurrence of other psychiatric disorders.
Lesná, J; Tichá, A; Hyšpler, R; Musil, F; Bláha, V; Sobotka, L; Zadák, Z; Šmahelová, A
Background: Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1. Methods: Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m−2, age 29–62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols—markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day. Results: Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03). Conclusion: Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism. PMID:26524638
Mehrabian, Sarvenaz; Taheri, Ehsaneh; Karkhaneh, Maryam; Qorbani, Mostafa; Hosseini, Saeed
Irisin, a recently identified myokine/adipokine, has potential role in type 2 diabetes and obesity. Normal weight obesity (NWO) is associated with a significantly higher risk of developing metabolic syndrome and cardiometabolic dysfunction. The aim of this study was to investigate association of irisin level with NWO, glycemicand lipid profile in women. In this matchedcase-control study, 38 subjects with NWO (body mass index (BMI) <25 kg/m2 and BF % > 30) as case and 26 controls (BMI <25 kg/m2 and BF % < 30) were selected randomly from sport clubs in the East area of Tehran, Iran. In addition to anthropometric variables, including BMI and body composition, fasting blood sugar (FBS), fasting levels of irisin andinsulin, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were measured. All statistical analyses were performed with SPSS 18.0. In univariate analysis, levels of irisin were significantly higher in subjects with NWO compared to controls (0.81 ± 0.41vs. 0.58 ± 0.26 ng/ml, P = 0.009). This association remained significant after adjusting for confounders (adjusted for energy intake, physical activity, waist circumference and BMI) (P = 0.049). In NWO, irisin level was not significantly correlated with all glycemic and lipid profile. In control group, only correlation ofirisin with insulin was statistically significant (P = 0.03). Serum irisin levels were higher in NWO subjects than controls. In control group, only the negative association between irisin and insulin levels was statistically significant. Further studies with larger sample size are clearly needed to evaluate the potential role of irisin in NWO subject and other disturbed metabolic conditions.
Jones, Ryan D; Lopez, Adam M; Tong, Ernest Y; Posey, Kenneth S; Chuang, Jen-Chieh; Repa, Joyce J; Turley, Stephen D
Mice deficient in cholesterol 7α-hydroxylase (Cyp7a1) have a diminished bile acid pool (BAP) and therefore represent a useful model for investigating the metabolic effects of restoring the pool with a specific BA. Previously we carried out such studies in Cyp7a1(-/-) mice fed physiological levels of cholic acid (CA) and achieved BAP restoration, along with an increased CA enrichment, at a dietary level of just 0.03% (w/w). Here we demonstrate that in Cyp7a1(-/-) mice fed chenodeoxycholic acid (CDCA) at a level of 0.06% (w/w), the BAP was restored to normal size and became substantially enriched with muricholic acid (MCA) (>70%), leaving the combined contribution of CA and CDCA to be <15%. This resulted in a partial to complete reversal of the main changes in cholesterol and BA metabolism associated with Cyp7a1 deficiency such as an elevated rate of intestinal sterol synthesis, an enhanced level of mRNA for Cyp8b1 in the liver, and depressed mRNA levels for Ibabp, Shp and Fgf15 in the distal small intestine. When Cyp7a1(-/-) and matching Cyp7a1(+/+) mice were fed a diet with added cholesterol (0.2%) (w/w), either alone, or also containing CDCA (0.06%) (w/w) or CA (0.03%) (w/w) for 18days, the hepatic total cholesterol concentrations (mg/g) in the Cyp7a1(-/-) mice were 26.9±3.7, 16.4±0.9 and 47.6±1.9, respectively, vs. 4.9±0.4, 5.0±0.7 and 6.4±1.9, respectively in the corresponding Cyp7a1(+/+) controls. These data affirm the importance of using moderate levels of dietary BA supplementation to elicit changes in hepatic cholesterol metabolism through shifts in BAP size and composition.
Wong, F L; Yamada, M; Sasaki, H; Kodama, K; Hosoda, Y
The effects of radiation on the long-term trends of the total serum cholesterol levels of the Hiroshima and Nagasaki atomic bomb survivors were examined using data collected in the Adult Health Study over a 28-year period (1958-1986). The growth-curve method was used to model the longitudinal age-dependent changes in cholesterol levels. For each sex, temporal trends of cholesterol levels were characterized with respect to age, body mass index, city and birth year. We then examined whether the temporal trends differed by radiation dose. We showed that the mean growth curve of cholesterol levels for the irradiated subjects were significantly higher than that for the unirradiated subjects, and that the increase was greater for women than for men. No difference in dose response was detected between Hiroshima and Nagasaki. An increased mean level of cholesterol was evident for irradiated women in general, but a notable increase was apparent in males only for the youngest birth cohort of 1935-1945. The difference in the mean cholesterol levels between the irradiated and unirradiated subjects diminished past 70 years of age. It is not known whether this is due to natural progression or is an artifact of nonrandom variation in the rate of participation in the examinations. The maximum predicted increase at 1 Gy for women occurred at age 52 years for the 1930 cohort: 2.5 mg/dl (95% CI 1.6-3.3 mg/dl) for Hiroshima and 2.3 mg/dl (95% CI 1.5-3.1 mg/dl) for Nagasaki. The corresponding increase for men occurred at age 29 years for the 1940 cohort: 1.6 mg/dl (95% CI 0.4-2.8) for Hiroshima and 1.4 mg/dl (95% CI 0.3-2.6) for Nagasaki. Controlling for cigarette smoking did not alter the dose-response relationship. Although the difference in the mean growth curves of the irradiated and unirradiated groups was statistically significant, there was a considerable overlap in the individual growth curves of the two groups. The significant sex difference and the greater magnitude of
Mesadi, Fitsum; Cetin, Mujdat; Tasdizen, Tolga
Level set methods are widely used for image segmentation because of their capability to handle topological changes. In this paper, we propose a novel parametric level set method called Disjunctive Normal Level Set (DNLS), and apply it to both two phase (single object) and multiphase (multi-object) image segmentations. The DNLS is formed by union of polytopes which themselves are formed by intersections of half-spaces. The proposed level set framework has the following major advantages compared to other level set methods available in the literature. First, segmentation using DNLS converges much faster. Second, the DNLS level set function remains regular throughout its evolution. Third, the proposed multiphase version of the DNLS is less sensitive to initialization, and its computational cost and memory requirement remains almost constant as the number of objects to be simultaneously segmented grows. The experimental results show the potential of the proposed method.
Mesadi, Fitsum; Cetin, Mujdat; Tasdizen, Tolga
Level set methods are widely used for image segmentation because of their capability to handle topological changes. In this paper, we propose a novel parametric level set method called Disjunctive Normal Level Set (DNLS), and apply it to both two phase (single object) and multiphase (multi-object) image segmentations. The DNLS is formed by union of polytopes which themselves are formed by intersections of half-spaces. The proposed level set framework has the following major advantages compared to other level set methods available in the literature. First, segmentation using DNLS converges much faster. Second, the DNLS level set function remains regular throughout its evolution. Third, the proposed multiphase version of the DNLS is less sensitive to initialization, and its computational cost and memory requirement remains almost constant as the number of objects to be simultaneously segmented grows. The experimental results show the potential of the proposed method.
Zhang, Ting; Li, He; Zhang, Junying; Li, Xin; Qi, Di; Wang, Nuo; Zhang, Zhanjun
Epidemiological and clinical studies suggest that high serum cholesterol is a risk factor of dementia. However, the effects of cholesterol on cognition and brain remain largely unclear. This study aims to investigate the associations between serum total cholesterol (TC) and neuropsychological performance, and intrinsic functional networks in non-demented elderly. Among a cohort of 120 community-dwelling Beijing residents, 29 subjects in the high-TC group (1st quartile) and 31 in the low-TC group (4th quartile) were included in this study, and underwent a battery of neuropsychological tests and magnetic resonance imaging (MRI) scans, including T2- and T1-weighted imaging, and resting-state functional MRI. No significant group difference was found in any of the neuropsychological tests used. Stronger connectivity in the default mode network was observed in the high-TC group compared to that in the low-TC group (p < 0.001, uncorrected). While in the salience network (SN), the high-TC group showed lower connectivity in the anterior cingulate cortex and frontal regions, compared to the low-TC group (p < 0.05, FWE corrected). Our findings suggest that in non-demented elderly persons, high serum cholesterol is associated with disruption of functional connectivity in the SN. The results not only deepen our understanding of how cholesterol affects the brain, but are also significant for selecting sensitive indicators for monitoring the impairments of cholesterol on the neural system.
Li, Xiaorong; Wang, Lijuan; Li, Yuhang; Ho, Yeung; Yang, Dongxu; Chen, Yi; Hu, Xiaomin; Xue, Ming
Polysorbates are amphiphilic, non-ionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan which are widely used in the cosmetic, food and pharmaceutical industries owing to these special characteristics and their low toxicity profiles. In the present study, polysorbates were investigated for their hypolipidemic activity. C57BL/6J mice and Sprague-Dawley rats were fed a high-fat diet for four weeks, then were divided into several groups, normal saline, polysorbates and positive control drugs such as lovastatin and colestyramine were administered orally to the animals for another four weeks. Complete lipid profiles of the experimental animals were determined by assessing the serum levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. The results indicate that polysorbates significantly lowered the lipid components. Polysorbates are potential candidates for preventing intestinal absorption of redundant lipid from daily intake and subsequently for preventing hyperlipidemia as well as atherosclerosis. Copyright © 2011 Elsevier B.V. All rights reserved.
Loh, Wan Ping; Yang, Yuansheng; Lam, Kong Peng
MicroRNAs (miRNAs) have emerged as promising targets for engineering of CHO cell factories to enhance recombinant protein productivity. Manipulation of miRNA levels in CHO cells have been shown to improve product yield by increasing proliferation and specific productivity (qP), resisting apoptosis and enhancing oxidative metabolism. The authors previously demonstrated that over-expressing miR-92a results in increases in qP and titer of CHO-IgG cells. However, the mechanisms by which miR-92a enhances qP in CHO cells are still uninvestigated. Here, the authors report the identification of insig1, a regulator of cholesterol biosynthesis, as a target of miR-92a using computational prediction. Both transient and stable over-expression of miR-92a decreased the expression levels of insig1. Insig1 was further validated as a target of miR-92a using 3' UTR reporter assay. Intracellular cholesterol concentration of two high-producing miR-92a clones were significantly increased by ≈30% compared to the blank-transfected pool. Relative Golgi surface area was also found to be 18-26% higher in these clones. Our findings suggest that miR-92a may affect cholesterol metabolism by repressing insig1, resulting in raised intracellular cholesterol levels and Golgi volume and hence enhanced protein secretion. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Ling, W H; Jones, P J
To investigate the action and mechanism of a dietary phytosterol mixture naturally containing sitostanol, derived from tall-oil, on circulating cholesterol and lipoprotein levels, five groups of rats were fed a control elemental diet (group 1), a control elemental diet with 1% cholesterol alone (group 2) or with sitostanol mixtures or a sitostanol-free mixture supplemented at 0.2% (group 3), 0.5% (group 4) or 1% (group 5) of dietary levels. One per cent supplementation of sitostanol (21%) compared with sitostanol-free mixtures decreased (P < 0.02) total serum cholesterol. Dietary sitostanol (16% or 21%) mixture at 1% dietary levels decreased (P < 0.05) low density lipoprotein (LDL) cholesterol and increased (P < 0.05) high density lipoprotein (HDL) cholesterol levels. The decrease of LDL and increase of HDL cholesterol were correlated (P < 0.01) with the level of sitostanol mixture in the diet. Consumption of the sitostanol-containing mixture (1% dietary levels) caused a compensatory increase in cholesterol synthesis as indicated by elevated (P < 0.05) lathosterol/ cholesterol ratios in plasma and hepatic cholesterol fractional synthesis rate (FSR) (P < 0.02). Both sitostanol and sitostanol-free mixtures at 0.5% or 1% dietary intake levels increased plasma campesterol and beta-sitosterol levels, while plasma sitostanol levels were negligible. The absence of sitostanol in plasma and the increase in cholesterol synthesis induced by dietary sitostanol mixtures in addition to elevation of plasma campesterol and beta-sitosterol by sitostanol or sitostanol-free mixtures suggest that sitostanol mixtures effectively modify circulating lipoprotein cholesterol concentrations at the level of the intestine, rather than internally at the level of cholesterogenesis.
... Artery Disease Venous Thromboembolism Aortic Aneurysm More About Cholesterol Updated:Jul 5,2017 Whether you’ve just ... Quiz This content was last reviewed April 2017. Cholesterol • Home • About Cholesterol Introduction Atherosclerosis What Your Cholesterol ...
... Room? What Happens in the Operating Room? What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? A A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...
Yang, Nan; Chung, Danna; Liu, Changda; Liang, Banghao; Li, Xiu-Min
The prevalence of obesity is increasing in industrialized countries. Obesity increases the risk of coronary artery disease, stroke, cancer, hypertension, and type-2 diabetes. Unfortunately, conventional obesity drug treatment is often associated with adverse effects. The objective of this study was to evaluate a novel natural formula, Weight loss herbal intervention therapy (W-LHIT), developed from traditional Chinese medicine, for weight control in a high-fat-diet (HFD) induced obesity murine model. Two sets of experiments were performed. In experiment 1, 14-week-old C57BL/6 J male mice were fed with HFD for 21 days and then separated into 3 weight-matched groups. One group continued on the HFD as obese-controls. Two groups were switched from HFD to normal fat level diet (NFD) and sham or W-LHIT treated. In experiment 2, 25-week-old obese mice, following 2 weeks acclimatization, received either W-LHIT or sham treatment while maintained on HFD. In both sets of experiments, NFD fed, age matched normal weight mice served as normal controls. Body weight and food intake were recorded. Epididymal fat pad weight, serum glucose and cholesterol levels, as well as PPARγ and FABP4 gene expression in epididymal fat tissue were analyzed at the end of the experiment. In experiment 1, W-LHIT treated obese mice lost body weight 12.2 ± 3.8% whereas sham treated mice lost 5.5 ± 2.8% by day 10 after switching from the HFD to the NFD, without reduction of chow consumption. In experiment 2, W-LHIT treated obese mice maintained on the HFD had significantly lower body weight (8 fold less) than the sham treated mice. W-LHIT treatment also reduced epididymal fat pad weight, blood cholesterol and glucose levels versus sham treated mice without reduced chow consumption. In addition, significantly increased PPARγ (peroxisome proliferator activated receptor γ) and FABP4 (fatty acid binding protein 4) gene expression were found in epdidymal fat tissues. Liver and kidney function and
Bruinse, H W; van den Berg, H
Most vitamin status parameters change significantly during pregnancy. A number of factors have been associated with this hypovitaminaemia of pregnancy. From our data, it was concluded that the initial value of a vitamin status parameter was by far the main determinant of the changes of vitamin levels during pregnancy: the higher the value, the steeper the decrease. Some hormonal variables were associated with these changes as well. This is highly suggestive of a resetting of vitamin homeostasis in blood, with a retention of vitamins in maternal tissues. The postpartum changes of vitamin levels provide insight into the 'net cost' of vitamins during pregnancy. Most serum blood levels of vitamins normalized shortly after delivery. Serum vitamin B6 levels increased slowly with 25% below the acceptable range at 6 months postpartum. However, the GGOT stimulation ratio, indicative for vitamin B6 cellular content, was completely normal at the time. Serum folacin was the only exception, with 45% serum levels in the marginal or deficient range; 20% of this group had deficient or marginal red cell folacin levels as well. This indicates that the 'net cost' of folacin during pregnancy is considerable, and repletion of folacin stores takes more than 6 months.
Sevelamer Does Not Decrease Lipopolysaccharide or Soluble CD14 Levels But Decreases Soluble Tissue Factor, Low-Density Lipoprotein (LDL) Cholesterol, and Oxidized LDL Cholesterol Levels in Individuals With Untreated HIV Infection
Sandler, Netanya G.; Zhang, Xinyan; Bosch, Ronald J.; Funderburg, Nicholas T.; Choi, Andrew I.; Robinson, Janet K.; Fine, Derek M.; Coombs, Robert W.; Jacobson, Jeffrey M.; Landay, Alan L.; Douek, Daniel C.; Tressler, Randall; Read, Sarah W.; Wilson, Cara C.; Deeks, Steven G.; Lederman, Michael M.; Gandhi, Rajesh T.
Abnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)–infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits. Clinical Trials Registration. NCT 01543958. PMID:24864123
Hagen, Ingrid V; Helland, Anita; Bratlie, Marianne; Brokstad, Karl A; Rosenlund, Grethe; Sveier, Harald; Mellgren, Gunnar; Gudbrandsen, Oddrun A
The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat.
Parlapiano, C; Paoletti, V; Campana, E; Giovanniello, T; Pantone, P; Labbadia, G; Califano, F; Donnarumma, L; Musca, A
Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide displaying about 50% homology with amylin which is secreted from the pancreatic islets of Langerhans. The main form, the beta-CGRP, is produced by the enteric nervous system and perivascular nerves of the vasa-vasorum. It represents one of the most powerful vasodilator yet discovered but its role is not yet completely clarified. High levels of this peptide have been shown in patients affected with thyroid medullary carcinoma, phaemocromocytoma and lung carcinoma. Recently circulating levels of CGRP have been found in normal subjects. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, isolated from porcine endothelial cells, is an important regulator of the vascular tone acting in physiological antagonism with atrial natriuretic hormone (ANH). With this study we intended to investigate the presence of any correlation between CGRP and ET-1 in normal subjects. For the study we considered 20 normal subjects (11 males and 9 females) aged 23 to 50. Plasma levels of CGRP and ET-1 were measured by radioimmunological Kit. A positive and significant correlation between calcitonin gene-related peptide and endothelin-1 was found. Our results confirms that CGRP and ET-1 have opposing actions on vessels and that they can act together in haemodinamic regulation.
... cholesterol levels with a blood test called a lipid profile. For the test, a nurse will take a ... blood tests that can check cholesterol, but a lipid profile gives the most information. Find out more about ...
Cuevas-Ramos, Daniel; Almeda-Valdés, Paloma; Chávez-Manzanera, Emma; Meza-Arana, Clara Elena; Brito-Córdova, Griselda; Mehta, Roopa; Pérez-Méndez, Oscar; Gómez-Pérez, Francisco J
Introduction Epidemiologic evidence suggests that tomato-based products could reduce the risk of cardiovascular diseases. One of the main cardiovascular risk factors is low levels of high-density lipoprotein cholesterol (HDL-C). This study aimed to prospectively evaluate the effect of tomato consumption on HDL-C levels. Subject and methods We conducted a randomized, single-blinded, controlled clinical trial. We screened 432 subjects with a complete lipid profile. Those individuals with low HDL-C (men <40 mg/dL and women <50 mg/dL) but normal triglyceride levels (<150 mg/dL) were included. Selected participants completed a 2-week run-in period on an isocaloric diet and then were randomized to receive 300 g of cucumber (control group) or two uncooked Roma tomatoes a day for 4 weeks. Results A total of 50 individuals (women = 41; 82%) with a mean age of 42 ± 15.5 years and a mean body mass index of 27.6 ± 5.0 kg/m2 completed the study. A significant increase in HDL-C levels was observed in the tomato group (from 36.5 ± 7.5 mg/dL to 41.6 ± 6.9 mg/dL, P < 0.0001 versus the control group). After stratification by gender, the difference in HDL-C levels was only significant in women. The mean HDL-C increase was 5.0 ± 2.8 mg/dL (range 1–12 mg/dL). Twenty patients (40%) finished the study with levels >40 mg/dL. A linear regression model that adjusted for those parameters that impact HDL-C levels (age, gender, waist-to-hip ratio, body mass index, fasting triglyceride concentration, simple sugars, alcohol, physical activity, and omega-3 consumption) showed an independent association between tomato consumption and the increase in HDL-C (r2 = 0.69; P < 0.0001). Conclusion Raw tomato consumption produced a favorable effect on HDL-C levels in overweight women. PMID:23935376
Devlin, Cecilia M; Kuriakose, George; Hirsch, Emmet; Tabas, Ira
Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls. IL-1ra transgenic/low-density lipoprotein receptor (LDLR) knockout mice fed a cholesterol-saturated fat diet for 10 wk showed a 40% increase in non-high-density lipoprotein cholesterol, consistent with the IL-1ra knockout data, although there was no change in lesion size. When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene. By immunohistochemistry, IL-1ra was present in C57BL/6J and LDLR knockout aortae, absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout/IL-1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size. These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development.
Nozaki, Yumi; Mitsumori, Toru; Yamamoto, Takeo; Kawashima, Ichiro; Shobu, Yuki; Hamanaka, Satoshi; Nakajima, Kei; Komatsu, Norio; Kirito, Keita
The introduction of rituximab, an anti-CD20 monoclonal antibody, has dramatically improved the treatment outcomes of patients with B cell lymphoma. Nevertheless, the clinical response to rituximab varies, and a subpopulation of patients does not respond well to this antibody. Although several molecular events have been shown to be involved in the mechanism of action of rituximab, recent studies have demonstrated that intracellular signaling pathways and the direct effects of rituximab on cell membrane components are responsible for the antilymphoma action of this drug. In the present study, we demonstrated that rituximab activated Syk and Akt, molecules with antiapoptotic functions, in several CD20-positive lymphoma cell lines. Notably, rituximab activated Syk and Akt in all the tested primary lymphoma samples from six patients. Our results show that the cholesterol levels in lymphoma cell membranes have a crucial role in the regulation of Syk and Akt. The depletion of cholesterol from the cell membrane completely blocked rituximab-induced Syk and Akt activation. Simvastatin, an inhibitor of cholesterol synthesis, also abrogated rituximab-mediated Syk and Akt activation. Finally, we report that rituximab inhibited the apoptosis induced by chemotherapeutic drugs, which was observed solely in Akt-activated cells. This work demonstrates for the first time that rituximab paradoxically works to suppress apoptosis under certain conditions in a manner that is dependent on the cell membrane cholesterol level. Our observations provide novel insights and suggest that the cell membrane cholesterol level represents a new biomarker for predicting patient response to rituximab. Furthermore, the modulation of lipid rafts could provide a new strategy for enhancing the antilymphoma action of rituximab. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
Khayat Nouri, Mir Hadi; Namvaran Abbas Abad, Ali
Background Hypercholesterolemia is one of the risk factors of cardiovascular diseases. Increased blood cholesterol affects general health and increases mortality due to cardiovascular disease. Poor nutrition increases LDL cholesterol and decreases LDL receptor activities in the liver. Scientists have shown that consumption of antioxidants can reduce hypercholesterolemia and proved benefits of fruit and vegetables. Tomato reduces oxidative stress by increasing serum total antioxidant level. Objectives This study compared the tomato and tomato paste supplementation on the level of serum lipids and lipoproteins in rats fed with high cholesterol. Materials and Methods In this study, four male rat groups (10 rats per group) were used. Control group received basal diet, second group received basal diet and 2% cholesterol (Chol), third and fourth groups received basal diet, 2% cholesterol tomato and tomato paste respectively (20 percent of the diet) for a month. Then serum TC, LDL, HDL and TG were measured. Results Results showed that in Chol group, all lipids increased significantly (P < 0.05) except HDL compared to the control group. Tomato and tomato paste supplementation decreased TC, LDL and TG concentration significantly (P < 0.05) compared to Chol group. Tomato paste had the higher effect on lipids decreasing than tomato. Conclusions Decreases of TC, LDL and TG may be related to tomato antioxidant effect. This course in human required more investigations. PMID:24082999
Jung, Dong-Hyuk; Lee, Yong-Jae; Lee, Hye-Ree; Lee, Jung-Hyun
Several studies have reported that hyperuricemia is associated with the development of hypertension and cardiovascular disease. Increasing evidences also suggest that hyperuricemia may have a pathogenic role in the progression of renal disease. Paradoxically, uric acid is also widely accepted to have antioxidant activity in experimental studies. We aimed to investigate the association between glomerular filtration rate (GFR) and uric acid in healthy individuals with a normal serum level of uric acid. We examined renal function determined by GFR and uric acid in 3,376 subjects (1,896 men; 1,480 women; aged 20-80 yr) who underwent medical examinations at Gangnam Severance Hospital from November 2006 to June 2007. Determinants for renal function and uric acid levels were also investigated. In both men and women, GFR was negatively correlated with systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, uric acid, log transformed C reactive protein, and log transformed triglycerides. In multivariate regression analysis, total uric acid was found to be an independent factor associated with estimated GFR in both men and women. This result suggests that uric acid appears to contribute to renal impairment in subjects with normal serum level of uric acid. PMID:21165292
Wang, Yanwen; Ebine, Naoyuki; Jia, Xiaoming; Jones, Peter J H; Fairow, Clint; Jaeger, Ralf
The aim of the current study was to examine the effects of very long chain fatty acids (VLCFA) alone at 2 dietary levels, or in combination of VLCFA at the lower level with lecithin (LT) or phytosterols (PS), on lipid profiles and cholesterol biosynthesis in hamsters. Seventy-five male Golden Syrian hamsters, weighing 100 to 120 g, were fed a regular rodent chow for 2 weeks before being randomly assigned into 5 groups of 15 animals each fed semisynthetic diets for 4 weeks. Group 1 was given a control diet that contained 0.25% cholesterol and 5% fat with a polyunsaturated to saturated fatty acids ratio of 0.4. Groups 2 to 5 were fed the control diet and given 25 mg/kg BW per day of VLCFA (Licowax) (VLCFA25), 50 mg/kg BW per day of VLCFA (VLCFA50), 25 mg/kg BW per day of VLCFA+1000 mg/kg BW per day of LT (VLCFA25/LT), and 25 mg/kg BW per day of VLCFA+1000 mg/kg BW per day of PS (Cholestatin, VLCFA25/PS), respectively. Results showed that HDL-cholesterol (HDL-C) levels were not changed by VLCFA25, although increased by VLCFA50 (P<.05) relative to control. Total cholesterol (T-C) and non-HDL-C levels were not affected by VLCFA25 and VLCFA50 as compared with control. VLCFA25/LT had higher (P<.02) T-C and HDL-C levels than any other treatments and increased (P<.05) liver weight relative to control. In contrast, VLCFA25/PS reduced T-C (P=.0004) and non-HDL-C (P=.007) without effect on HDL-C levels compared with control. Triglyceride levels were not affected by any treatment. Cholesterol biosynthesis rate was higher (P<.05) in animals fed VLCFA25 and VLCFA50 than those fed control or VLCFA25/LT or VLCFA25/PS. Results suggest that PSs can decrease total and non-HDL-C cholesterol, whereas VLCFA may increase HDL-C in hamsters.
Almeida-Montes, L G; Valles-Sanchez, V; Moreno-Aguilar, J; Chavez-Balderas, R A; García-Marín, J A; Cortés Sotres, J F; Hheinze-Martin, G
OBJECTIVE: To determine if there is a relation to low serum cholesterol, lipoprotein, serotonin or tryptophan levels in patients with depression who have recently attempted suicide. DESIGN: Biochemical and behavioural study. SETTING: Inpatient and outpatient treatment at the Instituto Mexicano de Psiquiatría. PARTICIPANTS: Thirty-three patients with a diagnosis of major depressive episode. Eighteen of these patients had attempted suicide in the month before the start of the study; 15 patients had never attempted suicide. OUTCOME MEASURES: Serum levels of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, serotonin (5-HT) and tryptophan. Scores on Hamilton Depression Rating Scale, Carroll Depression Rating Scale, Beck Hopelessness Scale and Beck Suicide Attempt Severity Scale. RESULTS: There were no significant differences between patients who had attempted suicide and those who had not in terms of serum cholesterol, HDL, LDL and triglyceride levels. Serum levels of 5-HT and tryptophan were significantly lower in patients with depression who had a recent suicide attempt than in those patients who had never attempted suicide. A comparison of patients not taking antidepressant medication found serum 5-HT levels to be more than 3 times lower in those patients with a recent suicide attempt than in patients with no history of suicide attempt. CONCLUSIONS: The study found no difference in lipid profiles between patients who had attempted suicide and those who had not. Low serum levels of 5-HT may increase the risk of suicide attempt in patients who are depressed. PMID:11022402
Frerichs, R R; Srinivasan, S R; Webber, L S; Berenson, G R
Serum lipid profiles of 3,446 (91% of population) children, ages 5-14 years, were determined in a biracial community (Bogalusa, Louisiana) as part of a program investigating the early natural history of atherosclerosis. Black children had significantly higher mean levels of serum cholesterol than white children (170 mg/dl vs 162 mg/dl, P less than 0.0001). On the other hand, significantly lower levels of triglycerides were found in blacks than in whites (61 mg/dl vs 73 mg/dl, P less than 0.0001). Girls had higher levels of triglycerides than boys in both races (blacks, 64 mg/dl vs 59 mg/dl, P less than 0.001; whites, 77 mg/dl vs 69 mg/dl, P less than 0.001). The racial differences in serum cholesterol and triglyceride levels were even more apparent at the 95th percentile. The serum cholesterol level remained relatively constant in all children until ages 11 and 12 years, after which a slight reduction occurred. This reduction was more pronounced in boys than in girls. In contrast, a significant increase in the level of triglycerides with age was observed in all children except black girls, the increasing slope being most pronounced in white girls.
Chambers, C M; McLean, M P; Ness, G C
A limitation to treating Smith-Lemli-Opitz infants by giving dietary cholesterol is their impaired ability to absorb cholesterol due to a deficiency of bile acids. Since intravenously administered lipoprotein cholesterol should not require bile acids for uptake into tissues, we tested the effects of this form of cholesterol on tissue cholesterol and 7-dehydrocholesterol levels in an animal model of SLO, created by feeding rats 0.02% AY 9944. Intravenous administration of 15 mg of bovine cholesterol supertrate twice daily increased serum cholesterol levels from 11 to over 250 mg/dl. This treatment increased liver cholesterol levels from 309 to over 900 micrograms/g and lowered hepatic 7-dehydrocholesterol levels from 1546 to 909 micrograms/g. A combination of iv cholesterol and 2% dietary cholesterol was most effective as it raised hepatic cholesterol levels to 1950 micrograms/g, which is 50% above normal. 7-Dehydrocholesterol levels were decreased to 760 micrograms/g. Similar responses were seen for heart, lung, kidney, and testes. Brain sterol levels were not significantly affected. AY 9944 caused a modest increase in hepatic HMG-CoA reductase activity. Administration of dietary cholesterol together with iv cholesterol lowered hepatic HMG-CoA reductase activity to barely detectable levels. The data indicate that the combination of iv and dietary cholesterol was most effective in raising cholesterol levels, lowering 7-dehydrocholesterol levels, and inhibiting de novo cholesterol biosynthesis.
Kim, Beom Joon; Lee, Seung-Hoon; Ryu, Wi-Sun; Kang, Bong Su; Kim, Chi Kyung; Yoon, Byung-Woo
Low cholesterol level is known to be associated with increased cerebral hemorrhage. However, the associations of hemorrhagic transformation (HTf) after acute ischemic stroke and the low levels of total cholesterol (TC) or low-density lipoprotein cholesterol (LDLC) are largely undiscovered. Of the 1034 patients with acute ischemic stroke who were consecutively admitted to our hospital, 377 patients with stroke attributable to large artery atherothrombosis (LAA; n=210) or cardioembolism (n=167) were selected for this study. Demographic and clinical information was collected and HTf was evaluated through follow-up T2*-weighted gradient-echo MRI performed usually within 1 week after stroke. Measurement of lipid parameters included TC, LDLC, high-density lipoprotein cholesterol, and triglyceride. Of the 377 patients, HTf was noted in 74 patients (19.6%). When patients were divided into 4 groups according to their TC and LDLC levels, the incidence of HTf was significantly elevated in the lowest quartile of each TC (P<0.01) and LDLC (P<0.01) level in LAA subgroup, but not in cardioembolism. After adjusting covariates, a low level of LDLC (OR, 0.46 per 1 mmol/L-increase; 95% CI, 0.22-0.98) was independently associated with HTf in LAA, but not in cardioembolism. There was no significant association between low levels of TC (OR, 0.63 per 1 mmol/L-increase; 95% CI, 0.35-1.15) and HTf in LAA. Low levels of LDLC, and possibly TC, are associated with greater risk of hemorrhagic transformation after acute ischemic stroke attributable to LAA.
Li, Xing; Tang, Hailin; Wang, Jin; Xie, Xinhua; Liu, Peng; Kong, Yanan; Ye, Feng; Shuang, Zeyu; Xie, Zeming; Xie, Xiaoming
Although dyslipidemia has been documented to be associated with several types of cancer including breast cancer, it remains uncertainty the prognostic value of serum lipid in breast cancer. The purpose of this study is to evaluate the association between the preoperative plasma lipid profile and the prognostic of breast cancer patients. The levels of preoperative serum lipid profile (including cholesterol [CHO], Triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoAI], and apolipoprotein B [ApoB]) and the clinical data were retrospectively collected and reviewed in 1044 breast cancer patients undergoing operation. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the overall survival [OS] and disease-free survival [DFS]. Combining the receiver-operating characteristic and Kaplan-Meier analysis, we found that preoperative lower TG and HDL-C level were risk factors of breast cancer patients. In multivariate analyses, a decreased HDL-C level showed significant association with worse OS (HR: 0.528; 95% CI: 0.302-0.923; P = 0.025), whereas a decreased TG level showed significant association with worse DFS (HR: 0.569; 95% CI: 0.370-0.873; P = 0.010). Preoperative serum levels of TG and HDL-C may be independent factor to predict outcome in breast cancer patient. Copyright © 2016 Elsevier Ltd. All rights reserved.
Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A.; Jacobs, Danny O.
Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies. PMID:24271489
Santacruz, Lucia; Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A; Jacobs, Danny O
Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.
Schartner, Matthias; Böhm, Johannes; Böhm, Sigrid; Schreiber, Karl Ulrich; Gebauer, André
Observations from ring laser gyroscopes can be used to continuously monitor earth rotation with high resolution and without an external reference frame, which makes them unique in contrast to other techniques like VLBI or GNSS. A combination, however, of ring laser and VLBI data could potentially result in an improved accuracy of estimated earth rotation parameters. In this study, we use observations from the ring laser "G" (Grossring) located at Wettzell (Germany) and combine them with VLBI observations at the normal equation level. The Vienna VLBI and Satellite Software (VieVS) is used to set up the normal equations for each VLBI session as SINEX files. We present combined estimates for polar motion and length of day and assess the impact by the ring laser observations.
Cayan, H.; Erener, G.
This experiment was conducted to measure the effects of olive leaf powder on performance, egg yield, egg quality and yolk cholesterol level of laying hens. A total of 120 Lohmann Brown laying hens of 22 weeks old were used in this experiment. The birds were fed on standard layer diets containing 0, 1%, 2%, or 3% olive leaf powder for 8 weeks. Egg weight and yield were recorded daily; feed intake weekly; egg quality and cholesterol content at the end of the trial. Olive leaf powder had no effect on feed intake, egg weight, egg yield and feed conversion ratio (p>0.05) while olive leaf powder increased final body weight of hens (p<0.05). Dietary olive leaf powder increased yellowness in yolk color (p<0.01) without affecting other quality parameters. Yolk cholesterol content was tended to decrease about 10% (p>0.05). To conclude, olive leaf powder can be used for reducing egg yolk cholesterol content and egg yolk coloring agent in layer diets. PMID:25656181
Ferreira, Guilherme Silva; Pinto, Paula R.; Iborra, Rodrigo T.; Del Bianco, Vanessa; Santana, Monique Fátima Mello; Nakandakare, Edna Regina; Nunes, Valéria S.; Negrão, Carlos E.; Catanozi, Sergio; Passarelli, Marisa
Background: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET) prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT) and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration. Methods: Sixteen-week old male apo E KO mice fed a chow diet were included in the protocol. Animals were trained in a treadmill running, 15 m/min, 5 days/week, for 60 min (T; n = 29). A control group was kept sedentary (S; n = 32). Plasma lipids and glucose were determined by enzymatic techniques and glucometer, respectively. Cholesterol and oxysterols in aortic arch and macrophages were measured by gas chromatography/mass spectrometry. The expression of genes involved in lipid metabolism was determined by RT-qPCR. The effect of AMPK in oxysterols metabolism was determined in J774 macrophages treated with 0.25 mM AICAR. Results: Body weight and plasma TC, TG, HDL-c, glucose, and oxysterols were similar between groups. As compared to S group, AET enhanced 7β-hydroxycholesterol (70%) and reduced cholesterol (32%) in aorta. In addition, exercise increased Cyp27a1 (54%), Cd36 (75%), Cat (70%), Prkaa1 (40%), and Prkaa2 (51%) mRNA. In macrophages, the activation of AMPK followed by incubation with HDL2 increased Abca1 (52%) and Cd36 (220%) and decrease Prkaa1 (19%), Cyp27a1 (47%) and 7α-hydroxycholesterol level. Conclusion: AET increases 7β-hydroxycholesterol in the aortic arch of dyslipidemic mice, which is related to the enhanced expression of Cd36. In addition, the increase and
Ferreira, Guilherme Silva; Pinto, Paula R; Iborra, Rodrigo T; Del Bianco, Vanessa; Santana, Monique Fátima Mello; Nakandakare, Edna Regina; Nunes, Valéria S; Negrão, Carlos E; Catanozi, Sergio; Passarelli, Marisa
Background: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET) prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT) and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration. Methods: Sixteen-week old male apo E KO mice fed a chow diet were included in the protocol. Animals were trained in a treadmill running, 15 m/min, 5 days/week, for 60 min (T; n = 29). A control group was kept sedentary (S; n = 32). Plasma lipids and glucose were determined by enzymatic techniques and glucometer, respectively. Cholesterol and oxysterols in aortic arch and macrophages were measured by gas chromatography/mass spectrometry. The expression of genes involved in lipid metabolism was determined by RT-qPCR. The effect of AMPK in oxysterols metabolism was determined in J774 macrophages treated with 0.25 mM AICAR. Results: Body weight and plasma TC, TG, HDL-c, glucose, and oxysterols were similar between groups. As compared to S group, AET enhanced 7β-hydroxycholesterol (70%) and reduced cholesterol (32%) in aorta. In addition, exercise increased Cyp27a1 (54%), Cd36 (75%), Cat (70%), Prkaa1 (40%), and Prkaa2 (51%) mRNA. In macrophages, the activation of AMPK followed by incubation with HDL2 increased Abca1 (52%) and Cd36 (220%) and decrease Prkaa1 (19%), Cyp27a1 (47%) and 7α-hydroxycholesterol level. Conclusion: AET increases 7β-hydroxycholesterol in the aortic arch of dyslipidemic mice, which is related to the enhanced expression of Cd36. In addition, the increase and
Boes, Eva; Coassin, Stefan; Kollerits, Barbara; Heid, Iris M; Kronenberg, Florian
High-density lipoprotein (HDL) particles exhibit multiple antiatherogenic effects. They are key players in the reverse cholesterol transport which shuttles cholesterol from peripheral cells (e.g. macrophages) to the liver or other tissues. This complex process is thought to represent the basis for the antiatherogenic properties of HDL particles. The amount of cholesterol transported in HDL particles is measured as HDL cholesterol (HDLC) and is inversely correlated with the risk for coronary artery disease: an increase of 1mg/dL of HDLC levels is associated with a 2% and 3% decrease of the risk for coronary artery disease in men and women, respectively. Genetically determined conditions with high HDLC levels (e.g. familial hyperalphalipoproteinemia) often coexist with longevity, and higher HDLC levels were found among healthy elderly individuals. HDLC levels are under considerable genetic control with heritability estimates of up to 80%. The identification and characterization of genetic variants associated with HDLC concentrations can provide new insights into the background of longevity. This review provides an extended overview on the current genetic-epidemiological evidence from association studies on genes involved in HDLC metabolism. It provides a path through the jungle of association studies which are sometimes confusing due to the varying and sometimes erroneous names of genetic variants, positions and directions of associations. Furthermore, it reviews the recent findings from genome-wide association studies which have identified new genes influencing HDLC levels. The yet identified genes together explain only a small amount of less than 10% of the HDLC variance, which leaves an enormous room for further yet to be identified genetic variants. This might be accomplished by large population-based genome-wide meta-analyses and by deep-sequencing approaches on the identified genes. The resulting findings will probably result in a re-drawing and extension of
Boes, Eva; Coassin, Stefan; Kollerits, Barbara; Heid, Iris M.; Kronenberg, Florian
High-density lipoprotein (HDL) particles exhibit multiple antiatherogenic effects. They are key players in the reverse cholesterol transport which shuttles cholesterol from peripheral cells (e.g. macrophages) to the liver or other tissues. This complex process is thought to represent the basis for the antiatherogenic properties of HDL particles. The amount of cholesterol transported in HDL particles is measured as HDL cholesterol (HDLC) and is inversely correlated with the risk for coronary artery disease: an increase of 1 mg/dL of HDLC levels is associated with a 2% and 3% decrease of the risk for coronary artery disease in men and women, respectively. Genetically determined conditions with high HDLC levels (e.g. familial hyperalphalipoproteinemia) often coexist with longevity, and higher HDLC levels were found among healthy elderly individuals. HDLC levels are under considerable genetic control with heritability estimates of up to 80%. The identification and characterization of genetic variants associated with HDLC concentrations can provide new insights into the background of longevity. This review provides an extended overview on the current genetic-epidemiological evidence from association studies on genes involved in HDLC metabolism. It provides a path through the jungle of association studies which are sometimes confusing due to the varying and sometimes erroneous names of genetic variants, positions and directions of associations. Furthermore, it reviews the recent findings from genome-wide association studies which have identified new genes influencing HDLC levels. The yet identified genes together explain only a small amount of less than 10% of the HDLC variance, which leaves an enormous room for further yet to be identified genetic variants. This might be accomplished by large population-based genome-wide meta-analyses and by deep-sequencing approaches on the identified genes. The resulting findings will probably result in a re-drawing and extension of
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...
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) have been associated with a decreased risk of these complications. The aim in this st...
Ware, Kathrine M
Cardiovascular disease is a leading cause of morbidity and mortality in the U.S. and around the globe. A large body of literature accumulated over the past several decades has shown the benefit of lowering serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels to reduce cardiovascular risk. National guidelines suggest therapeutic lifestyle changes, beginning with diet, as a first step toward lowering TC and LDL-C. It has been suggested a plant-based, low fat diet can substantially reduce TC and LDL- C and thereby reduce risk of cardiovascular disease. The purpose of this review is to examine the state of the science regarding the efficacy of plant-based diets in reducing serum TC and LDL-C levels. While results of the research review indicate some benefit, strong evidence supporting the efficacy of plant-based diet in reducing atherogenic lipids is lacking.
Dong, Xiao-Long; Liu, Tai-Hang; Wang, Wei; Pan, Cai-Xia; Du, Guo-Yu; Wu, Yun-Fei; Pan, Min-Hui; Lu, Cheng
B.mori nucleopolyhedrovirus (BmNPV), which produces BV and ODV two virion phenotypes in its life cycle, caused the amount of economic loss in sericulture. But the mechanism of its infection was still unclear. In this study we characterized B.mori nuclear hormone receptor 96 (BmNHR96) as a NHR96 family member, which was localized in the nucleus. We also found BmNHR96 over-expression could enhance the entry of BV as well as cellular cholesterol level. Furthermore, we validated that BmNHR96 increased membrane fusion mediated by GP64, which could probably promote BV-infection. In summary, our study suggested that BmNHR96 plays an important role in BV infection and this function probably actualized by affecting cellular cholesterol level, and our results provided insights to the mechanisms of BV-infection of B.mori.
Morita, Yasuko; Homma, Yasuhiko; Igarashi, Mihoko; Miyano, Ryuusuke; Yamaguchi, Hiroshi; Matsuda, Momoo; Tanigaki, Toshimori; Shiina, Yutaka; Homma, Koichiro
It has not been well defined whether plasma low-density lipoprotein cholesterol (LDL-C) progresses arteriolosclerosis (arteriosclerosis of small arteries) or not. Estimated glomerular filtration rate (e-GFR) is an indicator of the function of renal arterioles and capillaries of glomeruli. The relationship between e-GFR and plasma LDL-C was studied to estimate the effect of plasma LDL-C on the function of renal arterioles and capillaries of glomeruli to speculate the effect of plasma LDL-C on arteriolosclerosis. Major coronary risk factors; blood pressure, plasma lipids, and fasting plasma glucose were compared among 4 groups of examinees of a health evaluation and promotion center separated by e-GFR, namely, Control group, Group 1, 2, 3 from highest e-GFR to lowest e-GFR. Numbers of total male and female subjects were 4602 and 2920, respectively. Plasma LDL-C levels were significantly high in Group 2 and 3 in all male subjects and high in Group 1, 2, and 3 in male subjects with age of fifties, compared with Control group. Plasma LDL-C levels were significantly high in Group 1, 2, and 3 in all female subjects and high in Group 2 and 3 in female subjects with age of fifties, compared with Control group. Plasma levels of LDL-C were not significantly different at each years of age in subjects with age of fifties in both sex. BMI and waist circumference were higher in male subjects with low e-GFR but not in female subjects. Blood pressure and fasting plasma glucose were not high in subjects in Group 1, 2, and 3, compared with Control group in all subjects and subjects with age of fifties in both sex. We concluded that the high plasma level of LDL-C was the major risk factor among coronary risk factors to reduce GFR probably due to impairing the function of renal arterioles and capillaries of glomeruli in subjects with normal kidney function assessed by urinalysis and plasma creatinine. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
... Thromboembolism Aortic Aneurysm More How To Get Your Cholesterol Tested Updated:Apr 3,2017 Cholesterol plays a ... factors for heart disease and stroke . How is cholesterol tested? A cholesterol screening measures your level of ...
Senna, Azza Abo; Zedan, Magda; el-Salam, Gamal E Abd; el-Mashad, Ashraf I
The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy.
Senna, Azza Abo; Zedan, Magda; Abd El Salam, Gamal E.; El Mashad, Ashraf I.
Aim The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. Subjects and Methods In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Results Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Conclusion Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy. PMID:18382699
Straniero, Sara; Cavallini, Gabriella; Donati, Alessio; Metelli, Maria Rita; Tamburini, Ilaria; Pietrini, Pietro; Bergamini, Ettore
Levels of plasma cholesterol, particularly LDL cholesterol, increase with increasing age in humans and rodents. Feeding a fish oil-rich diet may exert hypocholesterolemic effects. The aim of this work was to examine the effects of a life-long administration of a PUFA-enriched diet and of a PUFA-deficient diet in male Sprague-Dawley rats on the age-associated increases in plasma cholesterol and triglycerides. Diet had small effects on body-weight, and had dramatic effects on liver phospholipids-fatty acids. Surprisingly, both diets counteracted the age-associated changes in plasma cholesterol and triglycerides similarly and benefits were already visible in adult rats.
Flynn, Shannon E; Gurm, Roopa; DuRussel-Weston, Jean; Aaronson, Susan; Gakenheimer, Lindsey; Smolarski, Joseph; Simhaee, Daniel; Corriveau, Nicole; Goldberg, Caren; Eagle, Taylor; Rao, Ravi M; Eagle, Kim A; Jackson, Elizabeth A
To examine factors associated with low high-density lipoprotein cholesterol (HDL-C) levels among middle school children. HDL-C levels were the primary outcome of interest. A total of 1,104 middle-school children (mean age 11.6 years, 51.2% female) were included in this analysis, of whom 177 (16%) had an HDL-C level ≤40 mg/dL. More than half of those with low HDL-C were overweight or obese (62.2%) and had greater systolic and diastolic blood pressure, triglyceride (TRG) levels, and low-density lipoprotein cholesterol levels compared with children with an HDL-C level >40 mg/dL. Among those with an HDL-C ≤ 40 mg/dL, 35% also had body mass index ≥85% and TRG levels ≥150 mg/dL. Exercise habits were significantly associated with HDL-C level, whereas sedentary behaviors, such as screen time, were not significantly associated with HDL-C level. Fruit and vegetable intake was also not significantly associated with HDL-C level. Children with low HDL-C levels are more likely to be overweight and to have other physiological indicators of increased cardiovascular risk. Further research is needed to determine if school-based interventions can result in long-term improvements in HDL-C.
Toledo-Ibelles, Paola; Franco, Martha; Carreón-Torres, Elizabeth; Luc, Gérald; Tailleux, Anne; Vargas-Alarcón, Gilberto; Fragoso, José Manuel; Aguilar-Salinas, Carlos; Luna-Luna, María; Pérez-Méndez, Oscar
The kidney has been proposed to play a central role in apo AI catabolism, suggesting that HDL structure is determined, at least in part, by this organ. Here, we aimed at determining the effects of a renal mass reduction on HDL size distribution, lipid content, and apo AI turnover. We characterized HDL subclasses in rabbits with a 75% reduction of functional renal mass (Nptx group), using enzymatic staining of samples separated on polyacrylamide electrophoresis gels, and also performed kinetic studies using radiolabeled HDL-apo AI in this animal model. Creatinine clearance was reduced to 35% after nephrectomy as compared to the basal values, but without increased proteinuria. A slight, but significant modification of the relative HDL size distribution was observed after nephrectomy, whereas cholesterol plasma concentrations gradually augmented from large HDL2b (+54%) to small HDL3b particles (+150%, P<0.05). Cholesteryl esters were the increased fraction; in contrast, free cholesterol phospholipids and triglycerides of HDL subclasses were not affected by nephrectomy. HDL-apo AI fractional catabolic rates were similar to controls. Reduction of functional renal mass is associated to enrichment of HDL subclasses with cholesteryl esters. Structural abnormalities were not related to a low apo AI turnover, suggesting renal contribution to HDL remodeling beyond being just a catabolic site for these lipoproteins. Copyright © 2013 Elsevier Inc. All rights reserved.
Ramakrishnan, Sadeesh K.; Taylor, Matthew; Qu, Aijuan; Ahn, Sung-Hoon; Suresh, Madathilparambil V.; Raghavendran, Krishnan; Gonzalez, Frank J.
Cholesterol synthesis is a highly oxygen-dependent process. Paradoxically, hypoxia is correlated with an increase in cellular and systemic cholesterol levels and risk of cardiovascular diseases. The mechanism for the increase in cholesterol during hypoxia is unclear. Hypoxia signaling is mediated through hypoxia-inducible factor 1α (HIF-1α) and HIF-2α. The present study demonstrates that activation of HIF signaling in the liver increases hepatic and systemic cholesterol levels due to a decrease in the expression of cholesterol hydroxylase CYP7A1 and other enzymes involved in bile acid synthesis. Specifically, activation of hepatic HIF-2α (but not HIF-1α) led to hypercholesterolemia. HIF-2α repressed the circadian expression of Rev-erbα, resulting in increased expression of E4BP4, a negative regulator of Cyp7a1. To understand if HIF-mediated decrease in bile acid synthesis is a physiologically relevant pathway by which hypoxia maintains or increases systemic cholesterol levels, two hypoxic mouse models were assessed, an acute lung injury model and mice exposed to 10% O2 for 3 weeks. In both models, cholesterol levels increased with a concomitant decrease in expression of genes involved in bile acid synthesis. The present study demonstrates that hypoxic activation of hepatic HIF-2α leads to an adaptive increase in cholesterol levels through inhibition of bile acid synthesis. PMID:24421394
Bleda, Silvia; de Haro, Joaquin; Varela, Cesar; Ferruelo, Antonio; Acin, Francisco
Soluble stimuli present in the plasma of patients with peripheral arterial disease (PAD) are capable of directly stimulating intracellular signalling in endothelium. Oxidized-LDL (oxLDL) induces NLRP3 inflammasome activation in macrophages. However, it is not clear how lipid profile affect NLRP1 inflammasome gene expression in endothelial cells. In this study, the effect of cholesterol and TG of plasma of patients with PAD on NLRP1 inflammasome gene expression in human arterial endothelial cells (HAECS) was assessed. We included 113 patients with symptomatic PAD. HAECs were stimulated for 2h using the plasma samples of the study participants. The NLRP1 quantification of the transcription was carried out on the 7500 real-time PCR system using the Taqman® Universal PCR Master Mix and Assays on demand. Relative quantification of the NLRP1 expression was carried out using the ΔΔCt (threshold cycle) comparative method. Plasma from patients with elevated VLDL-cholesterol levels (>33.6mg/dL, the median value of the sample) provoked a higher expression of NLRP1 inflammasome in HAECs (RQ=1.15±0.23 vs. 1.05±0.69; p=0.045), as well as plasma from patients with elevated TGs levels (>168mg/dL, the median value of the sample) (RQ=1.15±0.23 vs. 1.05±0.69; p=0.045). A positive correlation was found between NLRP1 inflammasome expression and VLDL-cholesterol plasma levels (r=0.4; p<0.001) as between NLRP1 inflammasome expression and TG levels (r=0.4; p<0.001). Plasma TG and VLDL cholesterol of patients with atherosclerosis, manifested as PAD, promote the in vitro NLRP1 inflammasome expression in HAECs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Iwaya, Hirokazu; Mizutani, Koichi; Ebihara, Tadashi; Wakatsuki, Naoto
Acoustical indoor positioning — a technology to locate objects or people inside a building using acoustical signals — is a key technology for contextual awareness and ubiquitous computing. To achieve simple localization, in this paper, we propose a transponder-based indoor positioning method. The proposed method does not require clock synchronization for accurate positioning. Furthermore, by using an adaptive signal level normalizer, the terminal can receive acoustic signals with appropriate levels resulting in accurate positioning. We designed a transponder-based indoor positioning method using audible sound and evaluated its performance in experiments. In experiments, three anchors (transponders) of known position are installed on a ceiling of an anechoic chamber, and positioning is performed by setting a terminal in various points. Positioning experiment results showed that the proposed method can achieve on the order of 0.08 ± 0.02 m positioning.
Cornelli, Umberto; Bondiolotti, Gianpietro; Battelli, Giovanna; Zanoni, Giuseppe; Finco, Annarosa; Recchia, Martino
Cheese is considered to increase the total cholesterol levels (CH) due to the high-saturated fat content. New models are needed to measure the relationship between cholesterol and cheese. Thirty different cheeses produced in Val Brembana, Italy ("furmai da mut", "caprino" and "stracchino"), were added to the diet of 30 groups of 4 rats. Cheeses were analyzed to differentiate the volatile organic compounds (VOCs) and the cholesterol content (Ch(f)). The body weight, CH, urine volume and oxidative balance were measured. Three new indexes in relation to CH were calculated: OI (oxidative index), PI (protective index) and OBRI (oxidative balance risk index). None of the cheeses increased CH. Some of the "furmai de mut" were significantly decreasing CH and improved the oxidative balance. Ch(f) was not affecting the CH levels in plasma. In terms of VOCs, the acetic acid content was correlated (p < 0.05) with the CH reduction and PI improvement. OBRI was reduced mainly in the "stracchino group". The model shows that some cheese can reduce significantly CH levels and improve the antioxidant capacity.
Khadapkar, S V; Sheth, N A; Bhide, S V
Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.
Pastori, Daniele; Baratta, Francesco; Carnevale, Roberto; Cangemi, Roberto; Del Ben, Maria; Bucci, Tommaso; Polimeni, Licia; Labbadia, Giancarlo; Nocella, Cristina; Scardella, Laura; Pani, Arianna; Pignatelli, Pasquale; Violi, Francesco; Angelico, Francesco
Objectives: Reduced vitamin E levels have been reported in patients with non-alcoholic steatohepatitis (NASH), but no conclusive data on patients with simple steatosis (SS) are available. Aim of this study was to investigate the association between serum vitamin E levels and SS. Methods: A cohort of 312 patients with cardio-metabolic risk factors was screened for liver steatosis by ultrasonography (US). We reasonably classified as SS patients with US-fatty liver, normal liver function tests (LFTs) and with Cytokeratin 18 <246 mIU/ml. Liver biopsy was performed in 41 patients with US-fatty liver and persistent elevation of LFTs (>6 months). Serum cholesterol-adjusted vitamin E (Vit E/chol) levels were measured. Results: Mean age was 53.9±12.5 years and 38.4% were women. Non-alcoholic fatty liver disease (NAFLD) was detected at US in 244 patients; of those 39 had biopsy-proven NASH and 2 borderline NASH. Vit E/chol was reduced in both SS (3.4±2.0, P<0.001), and NASH (3.5±2.1, P=0.006) compared with non-NAFLD patients (4.8±2.0 μmol/mmol chol). No difference was found between SS and NASH (P=0.785). After excluding patients with NASH, a multivariable logistic regression analysis found that Vit E/chol (odds ratio (OR): 0.716, 95% confidence interval (CI) 0.602–0.851, P<0.001), alanine aminotransferase (ALT, OR: 1.093, 95% CI 1.029–1.161, P=0.004), body mass index (OR: 1.162, 95% CI 1.055–1.279, P=0.002) and metabolic syndrome (OR: 5.725, 95% CI 2.247–14.591, P<0.001) were factors independently associated with the presence of SS. Conclusions: Reduced vitamin E serum levels are associated with SS, with a similar reduction between patients with SS and NASH, compared with non-NAFLD patients. Our findings suggest that the potential benefit of vitamin E supplementation should be investigated also in patients with SS. PMID:26426796
Eleftheriou, Phaedra; Tseka, Eros; Varaga, Evagelia; Nasiou, Margarita; Sampanis, Christos; Zografou, Ioanna; Oulorgia, Jensila; Damontsidou, Katerina; Zaimi, Terpsithea; Markou, Helen-Irene; Varsamidis, Kostantinos; Petrou, Christos; Limberaki, Eugenia; Ganou, Christina-Joulia
, triglyceride values were within normal range in both cases (123.7±63.2mg/dL in DM1 and 168.1±76.0mg/dL in DM2 patients). Cortisol levels were elevated in both cases with higher values observed in Diabetes type I (280.5±162.9ng/mL in DM1 and 248.5±100.1ng/mL in DM2), while total antioxidant capacity was significantly reduced compared to healthy individuals, 1.470mM, with lower values observed in Diabetes type I (0.680±0.116mM in DM1 and 0.849±0.126mM in DM2). Amylase determination revealed a mean amylase value, 81.7U/ml, within normal range and a negative correlation between cholesterol levels and amylase (r=-0.770) in DM1 patients. No correlation was observed between the determined values or the presence of autoantibodies and antibodies against Neu5Gc in the samples. In conlusion, the lipidemic profile and overall atherogenic and cardiovascular risk factors were worse in Diabetes I compared to Diabetes II patients. Most interestingly, cholesterol levels exhibited a negative correlation with serum amylase values. Since, amylase is not known to be involved in lipid metabolism, cholesterol levels and serum amylase activity may have a common modulator related to Diabetes development.
Song, J; He, J J; Fang, A P; Li, H; Guo, M H; Shen, X; Li, K J
Objective: To analyze the association between food intake and the serum total cholesterol(TC) level in adult Chinese population. Methods: This study included apparent healthy residents aged between 20 and 70 years who participated in the eighth round of China Health and Nutrition Study (CHNS) in 9 regions of China including Liaoning, Helongjiang, Shandong, Jiangsu, Henan, Hunan, Hubei, Guizhou provinces and Guangxi Zhuang Autonomous Region in 2009. The association between the serum TC level and the diet and other related factors were analyzed. Results: (1) Linear trend test showed that age, body mass index, waist circumference, systolic and diastolic blood pressure were positively related with serum TC level in 20-45 and 46-70 years old male and female (all P<0.01), while physical activity level was negatively related with serum TC level in 20-45 and 46-70 years old male and 46-70 years old female (all P<0.01). (2) Multivariate linear regression analysis showed that livestock meat intake was positively related with serum TC level in following populations: 20-45 years old male, β=0.133, P<0.001; 46-70 years old male, β=0.102, P=0.001; 20-45 years old male, β=0.065, P=0.041; years old female, β=0.059, P=0.045. Vegetable oil intake was negatively related with serum TC level in 20-45 years old male (β=-0.071, P=0.021). Saturated fat intake was positively related with serum TC level in 46-70 years old female (β=0.084, P=0.019). Total dietary cholesterol intake was positively related with serum TC level in male (20-45 years old, β=0.067, P=0.021; 46-70 years old, β=0.070, P=0.012), but not in female (20-45 years old, β=0.007, P=0.809; 46-70 years old, β=0.038, P=0.144). Cholesterol intake from livestock meat was positively related with serum TC level in male (20-45 years old, β=0.156, P<0.001; 46-70 years old, β=0.099, P=0.001), and positively related with serum TC level in 46-70 years old female (β=0.063, P=0.028). Cholesterol intake from egg was positively
Schiele, Felix; Park, John; Redemann, Norbert; Luippold, Gerd; Nar, Herbert
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of LDL (low-density lipoprotein) cholesterol. Autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease. The inhibition of PCSK9 function by therapeutic antibodies that block interaction of PCSK9 with the epidermal growth factor-like repeat A domain of LDL receptor (LDLR) was shown to successfully lower LDL cholesterol levels in clinical studies. Here we present data on the identification, structural and biophysical characterization and in vitro and in vivo pharmacology of a PCSK9 antibody (mAb1). The X-ray structure shows that mAb1 binds the module 1 of the C-terminal domain (CTD) of PCSK9. It blocks access to an area bearing several naturally occurring gain-of-function and loss-of-function mutations. Although the antibody does not inhibit binding of PCSK9 to epidermal growth factor-like repeat A, it partially reverses PCSK9-induced reduction of the LDLR and LDL cholesterol uptake in a cellular assay. mAb1 is also effective in lowering serum levels of LDL cholesterol in cynomolgus monkeys in vivo. Complete loss of PCSK9 is associated with insufficient liver regeneration and increased risk of hepatitis C infections. Blocking of the CTD is sufficient to partially inhibit PCSK9 function. Antibodies binding the CTD of PCSK9 may thus be advantageous in patients that do not tolerate complete inhibition of PCSK9.
Viana, M B; Giugliani, R; Leite, V H; Barth, M L; Lekhwani, C; Slade, C M; Fensom, A
Very low serum levels of high density lipoprotein cholesterol ranging from 8.6 to 13.9 mg/dl were detected in four out of 12 sibs of a Brazilian kindred with the non-neuropathic form of Niemann-Pick disease. Hepatosplenomegaly, interstitial infiltration of the lungs, absence of neurological signs, sea-blue histiocytes in the bone marrow and liver, and high values for serum acid phosphatase (18 to 32 U/l) were common to all affected children. Leucocyte acid sphingomyelinase activity ranged from 3.6 to 6.5% of mean control values, and fibroblast activity from 9 to 13% of mean controls. The parents had low-normal levels. The relationship between these findings is unclear and deserves further investigation. Images PMID:2120445
Trikash, Irene; Gumenyuk, Vitaliy; Kuchmerovska, Tamara
Diabetic neuropathy represents one of the most prevalent complications of diabetes mellitus. The aim of this study was to investigate the effect of diabetes-induced disturbances in neurons on the Ca(2+)-triggered membrane fusion process in cell-free system in relation to plasmalemma cholesterol level. The gabapentin therapy on the exocytosis process was also studied. The diabetes in rats was induced by streptozotocin (60 mg/kg of body weight, i.p.). After 4 weeks of diabetes induction the one group of diabetic rats was treated with gabapentin (50 mg/kg, i.p.) during 1 month. Fusion experiments were performed in the cell-free model system using fluorescent dye octadecylrhodamine B. The [2-(14)C]serotonin preloaded synaptosomes were used for assay of stimulated neurotransmitter release. The synaptosomal plasma membrane cholesterol level in diabetic rats was on 12 % higher than in control and was decreased on 5 % after gabapentin therapy. The rate of synaptic vesicles fusion with plasma membranes in the presence of Ca(2+) and synaptosomal cytosolic proteins was decreased to 14.5 % in diabetic rats as compared to control (23 %) and after gabapentin administration to diabetic rats was raised to 18 %. At diabetes the stimulated synaptosomal serotonin release was increased in 1.7-2 folds and was partially normalized by gabapentin therapy. Together, these findings suggest that elevated cholesterol content in neuronal plasma membranes at diabetes impairs the membrane fusion process in neurons that can induce the development of neuropathy. Diabetes-evoked impairments of the exocytotic process can be attenuated by gabapentin therapy.
Laurinavicius, Antonio G; Santos, Itamar S; Santos, Raul D; Bensenor, Isabela M; Conceição, Raquel D; Lotufo, Paulo A
There is evidence that extremely elevated high-density lipoprotein cholesterol (HDL-c), that is, hyperalphalipoproteinemia (HALP) may indicate dysfunctional HDL, conferring increased cardiovascular risk. We studied carotid intima-media thickness (cIMT) a marker of subclinical vascular disease according to HDL-c distribution. cIMT was studied in subjects with "normal" HDL-c levels (HDL-c 40-50 mg/dL for men; 50-60 mg/dL for women, mean 49.6 ± 5.7 mg/dL, n = 3226); in those with HALP (HDL-c ≥90 mg/dL for both sexes, mean 101.2 ± 10 mg/dL, n = 264) and according to HDL-c quintile distribution (n = 9779). Multiple linear regression was used to test the association of HDL-c and cIMT. Subjects with HALP were older (54.5 ± 9.6 vs 51.1 ± 8.8 years, P < .001); more frequently females (86.4% vs 49%, P < .001); and presented a lower burden of risk factors: hypertension (24.6% vs 32.7%, P = .009), diabetes (10.2% vs 20.4%, P < .001), and obesity (18.6% vs 37.6%, P < .001). A similar profile was seen with higher HDL-c quintiles in the whole study population. When compared to normal HDL-c values, HALP was associated with lower maximal cIMT (0.779 ± 0.189 mm vs 0.818 ± 0.200 mm, P = .002), and there was a lower prevalence of individuals with cIMT ≥ 75(th) percentile for age and gender or high cIMT (17.5% vs 26.2%, P = .003). After multivariate analysis, no association was seen between HALP and increasing cIMT values, indeed the 5(th) HDL-c quintile was associated with lower risk of high cIMT (OR = 0.80; 95% CI = 0.68-0.95). HALP is associated with lower cIMT and does not indicate a pro-atherogenic phenotype. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.
Hirata, Takumi; Sugiyama, Daisuke; Nagasawa, Shin-Ya; Murakami, Yoshitaka; Saitoh, Shigeyuki; Okayama, Akira; Iso, Hiroyasu; Irie, Fujiko; Sairenchi, Toshimi; Miyamoto, Yoshihiro; Yamada, Michiko; Ishikawa, Shizukiyo; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori
Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.
Montalti, D; Gutiérrez, Ana María; Reboredo, G R; Salibián, A
The uropygial gland is an organ typical of birds, over which no agreement regarding its function has been attained yet. Authors attribute to the gland an hydrophobic action. The function of the gland is herein explored in rock pigeon, Columba livia, was used as experimental model for trials. The study was focused on the physiological role of the gland in relation to biochemical parameters. Pigeons were separated in groups of six birds each: a) intact control, b) surgical control, c) ablationed. Comparing control specimens with gland-removed specimens, recorded serum levels after 32 days were the following (mean+/-SD): cholesterol (g/l), 3.7+/-0.6 vs. 4.1+/-0.6; total lipids (g/l), 15.7+/-2.0 vs. 13.7+/-2.7; calcium (mg/l), 100.5 +/- 24.3 vs. 99.1 +/- 9.2. None of the differences were statistically significant. Thus, no alterations of basic biochemical parameters associated with metabolism of lipids were registered. In one group of birds the calcium and cholesterol levels were determined 122 days after surgery; in this case values remained unchanged related to the beginning of the trials. Results suggest that the uropygial gland is not physiologically related to either the homeostasis of total lipids, cholesterol or the regulation of calcium metabolism.
Huang, Xuemei; Chen, Honglei; Miller, William C; Mailman, Richard B; Woodard, Jennifer L; Chen, Peter C; Xiang, Dong; Murrow, Richard W; Wang, Yi-Zhe; Poole, Charles
The apolipoprotein E (APOE) epsilon2 allele has been associated with both Parkinson's disease (PD) and lower low-density lipoprotein cholesterol (LDL-C). We tested the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 112 controls. The PD cases were recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and the controls were recruited from the spouse populations of the same clinic. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from unconditional logistic regressions, adjusting for age, gender, smoking status, and use of cholesterol-lowering agents. Lower LDL-C concentrations were associated with a higher occurrence of PD. Compared with participants with the highest LDL-C (> or =138 mg/dL), the OR was 2.2 (95% CI = 0.9-5.1) for participants with LDL-C of 115 to 137, 3.5 (95% CI = 1.6-8.1) for LDL-C of 93 to 114, and 2.6 (95% CI = 1.1-5.9) for LDL-C of < or = 92. Interestingly, use of either cholesterol-lowering drugs, or statins alone, was related to lower PD occurrence. Thus, our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence, either of which finding warrants further investigation.
Sher, Alam; Fakhar-ul-Mahmood, Muhammad; Shah, Syed Nisar Hussain; Bukhsh, Sattar; Murtaza, Ghulam
Comparative hypoglycemic and hypolipidaemic activity of garlic (ethanol) extract and metformin was the aim of the study in 24 normal and diabetic rabbits. In group A of 12 rabbits, the influence of different doses (250, 300 and 350 mg/kg body weight) of garlic extract was evaluated, six of them were kept normal, while six were caused to be diabetic with alloxan (150 mg/kg body weight). In another group B of 12 rabbits, the influence of various doses of metformin (250, 375 and 500 mg/kg body weight) was also assessed in the similar grouping of six normal and six diabetic rabbits. The maximum hypoglycemic response was observed with highest doses of garlic extract (350 mg/kg body weight) in normal rabbits 4 h after garlic extract administration, while in diabetic rabbits, blood glucose level (270.3 ± 0.8 mg/dl) was significantly (p < 0.05) lowered as compared to the control level (303.8 ± 1.8 mg/dl). The levels of triglycerides (44.0 ± 0.9 mg/dl) and cholesterol (32.8 ± 0.7 mg/dl) also significantly (p < 0.05) decreased in normal rabbits after 4 h of extract administration as compared to that of 0 h samples (triglycerides 66.0 ± 1.5 mg/dl and cholesterol 47.5 ± 0.5 mg/dl). In diabetic rabbits, 0 h level of triglyceride and cholesterol was found to be 86.5 ± 1.1 mg/dl and 93.8 ± 0.9 mg/dl, respectively and levels seen in 4 h sample were 61.3 ± 1.2 mg/dl and 57.0 ± 1.8 mg/dl, respectively. In normal as well as diabetic rabbits, garlic extract produced hypoglycemia as well as hypolipidaemia like metformin, but the hypoglycemic effect was more pronounced with metformin, whereas garlic extract was more effective in causing hypolipidaemia as compared to metformin.
Aizawa, Koichi; Inakuma, Takahiro
The effects of dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), on lipid metabolism were examined. Young male Wistar rats were fed diets containing paprika powder, paprika organic solvent extract, residue of paprika extract, and purified capsanthin. Administration of purified capsanthin for 2 weeks resulted in a significant increase in plasma HDL-cholesterol (P < 0.05) without detectable differences in plasma total cholesterol and TAG concentrations. A statistically significant correlation (r 0.567; P < 0.001) was found between dietary capsanthin concentrations and plasma HDL-cholesterol concentrations. Animals receiving diets containing two different capsanthin concentrations exhibited dose-dependent increases in plasma HDL-cholesterol (r 0.597; P < 0.005). While capsanthin was absent in the liver of animals fed the basal diet, it increased markedly in capsanthin-fed animals (P < 0.001). Quantitative analyses of hepatic mRNA levels revealed that capsanthin administration resulted in up-regulation of mRNA for apoA5 and lecithin cholesterol acyltransferase (LCAT), without significant differences in other mRNA levels related to HDL-cholesterol metabolism. These results suggest that capsanthin had an HDL-cholesterol-raising effect on plasma, and the potential to increase cholesterol efflux to HDL particles by increasing apoA5 levels and/or enhancement of LCAT activity.
Zuliani, G; Cavalieri, M; Galvani, M; Volpato, S; Cherubini, A; Bandinelli, S; Corsi, A M; Lauretani, F; Guralnik, J M; Fellin, R; Ferrucci, L
To evaluate the association between plasma lipid fractions and the prevalence of dementia in a large sample of Italian older individuals. A total of 1051 older community-dwelling individuals (age >/=65 years), enrolled in the InChianti study, were included. Diagnosis of dementia was established at baseline and at the 3-year follow-up using Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria. Plasma lipids were measured by standardized methods at baseline and after 3 years. At baseline, 61 individuals (5.8%) were affected by dementia. Demented individuals showed significantly lower total cholesterol (TC), nonhigh-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels compared with controls; no differences were found in triglycerides (TG) and lipoprotein (a) levels. Of the 819 subjects reevaluated at the 3-year follow-up, 81 (9.9%) received a new diagnosis of dementia. Again, demented subjects were characterized by significantly lower TC, non-HDL-C, and HDL-C levels compared with controls, thus confirming the baseline findings. At multivariate logistic regression analysis, HDL-C levels (odds ratio: 0.96, 95% confidence interval: 0.93-0.99), but not TG and non-HDL-C, were associated with dementia independent of important confounders including age, gender, apo E phenotype, stroke, weight loss, interleukin 6 levels, and ankle-brachial index. Among community-dwelling older people, individuals affected by dementia showed significantly lower TC, non-HDL-C, and HDL-C levels; however, at multivariate analysis, only HDL-C was associated with dementia. Our results suggest the existence of an independent relationship between dementia and low HDL-C levels.
Cavalieri, M.; Galvani, M.; Volpato, S.; Cherubini, A.; Bandinelli, S.; Corsi, A. M.; Lauretani, F.; Guralnik, J. M.; Fellin, R.; Ferrucci, L.
Background. To evaluate the association between plasma lipid fractions and the prevalence of dementia in a large sample of Italian older individuals. Methods. A total of 1051 older community-dwelling individuals (age ≥65 years), enrolled in the InChianti study, were included. Diagnosis of dementia was established at baseline and at the 3-year follow-up using Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria. Plasma lipids were measured by standardized methods at baseline and after 3 years. Results. At baseline, 61 individuals (5.8%) were affected by dementia. Demented individuals showed significantly lower total cholesterol (TC), nonhigh–density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels compared with controls; no differences were found in triglycerides (TG) and lipoprotein (a) levels. Of the 819 subjects reevaluated at the 3-year follow-up, 81 (9.9%) received a new diagnosis of dementia. Again, demented subjects were characterized by significantly lower TC, non-HDL-C, and HDL-C levels compared with controls, thus confirming the baseline findings. At multivariate logistic regression analysis, HDL-C levels (odds ratio: 0.96, 95% confidence interval: 0.93–0.99), but not TG and non-HDL-C, were associated with dementia independent of important confounders including age, gender, apo E phenotype, stroke, weight loss, interleukin 6 levels, and ankle–brachial index. Conclusions. Among community-dwelling older people, individuals affected by dementia showed significantly lower TC, non-HDL-C, and HDL-C levels; however, at multivariate analysis, only HDL-C was associated with dementia. Our results suggest the existence of an independent relationship between dementia and low HDL-C levels. PMID:20299544
Nemoto, Kiyomitsu; Ikeda, Ayaka; Ito, Sei; Miyata, Misaki; Yoshida, Chiaki; Degawa, Masakuni
Serum total cholesterol amounts in the stroke-prone hypertensive rat (SHRSP) strain are lower than in the normotensive control strain, Wistar-Kyoto (WKY) rat. To understand the strain difference, constitutive gene expression levels of hepatic cholesterol biosynthetic enzymes in male 8-week-old SHRSP and WKY rats were comparatively examined by DNA microarray and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. Of 22 cholesterol biosynthetic enzyme genes, expression levels of 8 genes, Pmvk, Idi1, Fdps, Fdft1, Sqle, Lss, Sc4mol, and Hsd17b7, in SHRSP were less than 50% those of the WKY rats; especially, the expression level of Sqle gene, encoding squalene epoxidase, a rate-limiting enzyme in cholesterol biosynthesis pathway, was about 20%. The gene expression level of sterol regulatory element-binding protein-2 (SREBP-2), which functions as a transcription factor upregulating gene expression of cholesterol biosynthetic enzymes, in SHRSP was about 70% of that in WKY rats. These results demonstrate the possibility that the lower serum total cholesterol level in SHRSP is defined by lower gene expression of most hepatic cholesterol biosynthetic enzymes. In particular, decreased gene expression level of Sqle gene might be the most essential factor. Moreover, the broad range of lowered rates of these genes in SHRSP suggests that the abnormal function and/or expression not only of SREBP-2 but also of one or more other transcription factors for those gene expressions exist in SHRSP.
Tiwari, Uma; Cummins, Enda
A meta-analysis was performed on epidemiologic studies to assess the relation between β-glucan consumption from oats and from barley on blood cholesterol level, triglyceride/triacylglycerol (TGL/TAG) level, and blood glucose level (BGL) in humans. In addition, the effect of β-glucan on total cholesterol (TC) and BGL was translated into an empirical dose-response model. Thirty research articles that evaluated the effect of different exposure levels of β-glucan on blood cholesterol and BGL were analyzed, yielding 126 clinical studies. There was a significant inverse relation in TC (-0.60 mmol/L, 95% confidence interval [CI] -0.85 to -0.34), low-density lipoprotein (-0.66 mmol/L, 95% CI -0.96 to -0.36), and TGL/TAG (-0.04 mmol/L, 95% CI -0.15 to 0.07) after consumption of β-glucan. In contrast, an increase in high-density lipoprotein cholesterol was noted (0.03 mmol/L, 95% CI -0.06 to 0.13) with the random-effect model. The analysis showed a significant change in BGL (-2.58 mmol/L, 95% CI -3.22 to -1.84) with high heterogeneity between (I(2) = 97%) and across (τ(2) = 5.88) the studies. The fixed-effect model showed a significant change in TC, low-density lipoprotein, and BGL, whereas it showed no significant changes in high-density lipoprotein and TGL/TAG. The dose-response model showed that a 3-g/d dose of oat or barley β-glucan was sufficient to decrease TC. Consumption of 3 g/d of oat or barley β-glucan is sufficient to decrease blood cholesterol, whereas the effect on BGL is still inconclusive, with high heterogeneity, and requires further clinical research studies with longer intervention periods. Copyright © 2011 Elsevier Inc. All rights reserved.
Naito, Hisao; Kamijima, Michihiro; Yamanoshita, Osamu; Nakahara, Ai; Katoh, Takahiko; Tanaka, Naoki; Aoyama, Toshifumi; Gonzalez, Frank J; Nakajima, Tamie
Peroxisome proliferator-activated receptor alpha (PPARA alpha) plays a pivotal role in lipid metabolism. Our previous study reported that PPARA-V227A was a major polymorphism in Japanese, which was associated with markedly lower serum total cholesterol (TC) levels, which were significantly affected by alcohol drinking compared to subjects with the wild-type (PPARA-WT) allele. However, serum lipids are also associated with aging and exercise frequency. The objective of the present study was to evaluate the relationship between PPARA-V227A and these factors. Genetic analysis of the polymorphism was performed in 1058 Japanese men and 281 women, and the relationship with aging, drinking and exercise on serum lipids was analyzed in 989 men and 245 women after exclusion criteria had been applied. In men, drinking increased high-density lipoprotein cholesterol (HDL-C) levels in both PPARA-WT and A227 carriers, but to a significantly higher degree in the latter. In women, TC and low-density lipoprotein cholesterol (LDL-C) levels in the A227 carriers drinking at least once a week were significantly higher than in PPARA-WT carriers. TC and LDL-C levels in males with PPARA-WT increased with aging regardless of drinking habit, while LDL-C levels in the A227 drinking carriers were significantly lower in 45-yr-old or older subjects than in 35- to 45-yr-olds. In addition, no effect of exercising was observed in the A227 carriers, while increase in the HDL-C of the PPARA-WT carriers was exercise frequency dependent. These results suggest that the influence of drinking, aging or exercise on TC, LDL-C and HDL-C levels in the A227 carriers may be different from those in the PPARA-WT subjects.
Zhang, Z B; Xue, Z X; Wu, X J; Wang, T M; Li, Y H; Song, X L; Chao, X F; Wang, G; Nazibam, Nurmamat; Ayxamgul, Bawudun; Gulbahar, Elyas; Zhou, Z Y; Sun, B S; Wang, Y Z; Wang, M
Objective: To understand the prevalence of dyslipidemia and normal blood lipids level in Uygur diabetes patients in Kashgar prefecture in southern area of Xinjiang. Methods: A total of 5 078 local residents aged ≥18 years (42.56% were men) selected through cluster random sampling in Kashgar were surveyed by means of questionnaire survey, physical examination and laboratory test, and 521 diabetes patients were screened. Results: The overall prevalence of dyslipidemia in diabetes patients was 59.50% (310/521) with adjusted rate as 49.39%. Age ≥65 years, overweight, obesity and abdominal obesity increased the risk for dyslipidemia by 0.771 times (95% CI: 1.015-3.088), 1.132 times (95% CI: 1.290-3.523), 1.688 times (95% CI: 1.573-4.592) and 0.801 times (95% CI: 1.028-3.155) respectively. Compared with males, female was a protective factor for dyslipidemia (OR=0.507, 95%CI: 0.334-0.769). The overall normal rate of blood lipids level including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) for type 2 diabetes patients was 11.13%. Female, higher BMI and abdominal obesity were the factors influencing the overall normal blood lipids level. The normal rate of LDL-C level decreased with increase of age, BMI and waist circumferences (trend test χ(2)=18.049, P<0.001; trend test χ(2)=10.582, P=0.001; χ(2)=19.081, P<0.001), but increased with educational level (trend test χ(2)=9.764, P=0.002). Conclusion: The prevalence of dyslipidemia in Uygur diabetes patients in Kashgar was high, however, the overall normal rate of blood lipid level was relatively low. Obesity was the most important risk factor for dyslipidemia in this area. More attention should be paid to dyslipidemia prevention in women.
Marzec, Magdalena E; Wojtysiak, Dorota; Połtowicz, Katarzyna; Nowak, Joanna; Pedrys, Roman
The quality of chicken meat, which is one of the most widely consumed meats in the world, has been the subject of research and studies for many years. There are several ways to improve the quality of this type of meat, including changing the concentrations of individual molecular components. Such important components of meat are inter alia, cholesterol, vitamin E, and some fatty acids such as ω-3 and ω-6. Manipulation of ingredient levels may be achieved by enriching chicken feed with elements of different types such as vegetable oils, garlic, or selenium. Thus far, various biochemical and biophysical methods have been used to study quality of different meat types, especially broiler meat. Here, the authors demonstrate the use of high-resolution time-of-flight secondary ion mass spectrometry (TOF-SIMS) mass spectrometry to assess how variations in animal nutrition affect concentrations of specific lipids in the meat, such as cholesterol and vitamin E. In the presented experiment, there were four different dietary treatments. Feed for animals in the first group was supplemented with soy oil in 50%, the second group's feed was supplemented with linseed oil in 50%, a combination of these two oils in the proportion of 44%:56% was used for the third group, and in the reference group, animals were fed with beef tallow. From each group, four individuals were selected for further analysis. Positive and negative ion mass spectra were generated from the pectoralis superficialis muscle tissue of the left carcass side of each one animal. Using TOF-SIMS with a bismuth cluster ion source (Bi3 (+)), and based on characteristic peaks for cholesterol in the positive mode and vitamin E in the negative mode, the authors have illustrated the relationship of these lipids levels to the various feeding regimens. Simultaneously, the authors characterized the varying dependences on the concentrations of measured lipids in fat and muscle fibers. The cholesterol concentration in muscle
St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH
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
Normal phase liquid chromatography coupled to quadrupole time of flight atmospheric pressure chemical ionization mass spectrometry for separation, detection and mass spectrometric profiling of neutral sphingolipids and cholesterol.
Farwanah, Hany; Wirtz, Jennifer; Kolter, Thomas; Raith, Klaus; Neubert, Reinhard H H; Sandhoff, Konrad
Many lipidomic approaches focus on investigating aspects of sphingolipid metabolism. Special emphasis is put on neutral sphingolipids and cholesterol and their interaction. Such an interest is attributed to the fact that those lipids are altered in a series of serious disorders including various sphingolipidoses. High performance thin-layer chromatography (HPTLC) has become a widely used technique for lipid analysis. However, mass spectrometric profiling is irreplaceable for gaining an overview about the various molecular species within a lipid class. In this work we have developed a sensitive method based on a gradient normal phase high performance liquid chromatography (HPLC) coupled to quadrupole time of flight (QTOF) atmospheric pressure chemical ionization mass spectrometry (APCI-MS) in positive mode, which for the first time enables separation, on-line detection, and mass spectrometric profiling of multiple neutral sphingolipids including ceramide, glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, sphingomyelin as well as cholesterol within less than 15min. An important advantage of the presented HPLC/APCI-MS approach is that the separation pattern emulates the one obtained by an optimized HPTLC method with a multiple stage development. Thus, the lipid classes previously separated and quantified by HPTLC can be easily screened regarding their mass spectrometric profiles by HPLC/APCI-MS. In addition, the selected ionization conditions enable in-source fragmentation providing useful structural information. The methods (HPLC/APCI-MS and the optimized HPTLC) were applied for the analysis of the mentioned lipids in human fibroblasts. This approach is aimed basically at investigators who perform studies based on genetic modifications or treatment with pharmacological agents leading to changes in the biochemical pathways of neutral sphingolipids and cholesterol. In addition, it can be of interest for research on disorders related to
Pezzini, Alessandro; Grassi, Mario; Iacoviello, Licia; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Del Sette, Massimo; Toriello, Antonella; Gandolfo, Carlo; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna; Chiti, Alberto; Calabrò, Rocco Salvatore; Musolino, Rossella; Bovi, Paolo; Tomelleri, Giampaolo; Di Castelnuovo, Augusto; Vandelli, Laura; Ritelli, Marco; Agnelli, Giancarlo; De Vito, Alessandro; Pugliese, Nicola; Martini, Giuseppe; Lanari, Alessia; Ciccone, Alfonso; Lodigiani, Corrado; Malferrari, Giovanni; Del Zotto, Elisabetta; Morotti, Andrea; Costa, Paolo; Poli, Loris; De Giuli, Valeria; Bonaiti, Silvia; La Spina, Paolo; Marcello, Norina; Micieli, Giuseppe; de Gaetano, Giovanni; Colombi, Marina; Padovani, Alessandro
Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Wilson, Stephen; Ginger, Rebecca S; Dadd, Tony; Gunn, David; Lim, Fei-Ling; Sawicka, Magdalena; Sandel, Melanie; Schnetkamp, Paul P M; Green, Martin R
Natural human skin colour is determined both by environmental exposure to ultraviolet light and through inherited genetic variation in a very limited number of genes. Variation of a non-synonymous single-nucleotide polymorphism (nsSNP; rs1426654) in the gene (SLC24A5) encoding the NCKX5 protein is associated with differences in constitutive skin colour in South Asians. The nsSNP encodes the substitution of alanine for threonine at residue 111 (A111T) near a transmembrane region required for exchanger activity, a region which is highly conserved across different species and between NCKX family members. We have shown that NCKX5 is located at the trans-Golgi network of melanocytes and functions as a potassium-dependent sodium-calcium exchanger. When heterologously expressed, the 111T variant of NCKX5 shows significantly lower exchanger activity than the A111 variant. We have postulated that lower exchanger activity causes the reduced melanogenesis and lighter skin in Thr111-positive individuals. We used gene expression microarrays with qPCR replication and validation to assess the impact of siRNA-mediated knockdown of SLC24A5 on the transcriptome of cultured normal human melanocytes (NHM). Very few genes associated with melanogenesis were altered at the transcript level except for MC1R, suggesting that SLC24A5 interacts with at least one well-characterized melanogenic signalling pathway. More surprisingly, the expression of a number of cholesterol homeostatic genes was altered after SLC24A5 knockdown, and the total cholesterol content of NHM was increased. Cholesterol has previously been identified as a potential melanogenic regulator, and our data imply that NCKX5 exchanger function influences natural variation in skin pigmentation via a novel, unknown mechanism affecting cellular sterol levels.
Saeedi, Ramesh; Li, Min; Allard, Matt; Frohlich, Jiri
Low-density lipoprotein cholesterol (LDL-C) is usually calculated using the Friedewald equation. However, this calculation method does not account for the cholesterol associated with lipoprotein(a) [Lp(a)]. Using the Dahlen equation, Li et al. have shown a strong positive correlation between serum Lp(a) levels and overestimation of LDL-C levels. To determine how the extreme levels of Lp(a) influence the LDL-C calculation. We performed a retrospective chart review of the lipid profile and Lp(a) of 223 patients (men and women). LDL-C was calculated using the Friedewald equation. Lp(a) concentrations were measured by an ELISA. Other serum lipids were measured enzymatically by standard methodology. Corrected LDL-C was calculated using the Dahlen equation. We found that this overestimation is very significant in individuals with extreme levels of Lp(a) (mean overestimation of 40% at Lp(a) >1200mg/L). Calculated LDL-C is markedly overestimated in patients with extreme levels of Lp(a). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Jukema, J W; Simoons, M L
In the beginning of this century a possible relation was observed between cholesterol-rich foods, blood cholesterol levels and atherosclerosis by "pioneers" in this field as Anitschkow and De Langen. In the second half of this century a definite link was established between serum cholesterol levels and development of coronary heart disease (CHD). In angiographic studies it has recently been shown that a decrease in total cholesterol as well as in low-density lipoprotein cholesterol level results in a retardation of the progression of vascular disease. Furthermore, clinical event intervention trials demonstrated that therapy with cholesterol synthesis inhibitors reduces not only cardiovascular and total mortality, but also other manifestations of CHD. These recent results prompted to revise, for the second time, the Dutch consensus text for lipid lowering therapy, with the following conclusions. Hypercholesterolaemia is treated with a low-saturated fat diet and normalisation of weight. For individuals, this might result in a reduction of the risk for myocardial infarction or death and for the population in a decrease of the mean serum cholesterol concentration and a reduction of the incidence of CHD. The indication for drug therapy is founded on the expected effectiveness to reduce the incidence of (new manifestations of) CHD, which is related to the level of the absolute risk of vascular disease. Treatment with cholesterol synthesis inhibitors must be considered in (a) patients with familial hypercholesterolaemia; (b) all patients with a history of myocardial infarction or other symptomatic vascular disease with a total cholesterol concentration above 5.0 mmol/l and a life expectancy of at least five years; (c) persons without known vascular disease with a combination of diabetes mellitus, hypertension, hypercholesterolaemia, cigarette smoking and high risk for development of CHD, rising from 25% per 10 years at the age of 40 years to 35-40% per 10 years at the age
Faust, Phyllis L; Kovacs, Werner J
Cholesterol biosynthesis is a multi-step process involving more than 20 enzymes in several subcellular compartments. The pre-squalene segment of the cholesterol/isoprenoid biosynthetic pathway is localized in peroxisomes. This review intends to highlight recent findings illustrating the important role peroxisomes play in cholesterol biosynthesis and maintenance of cholesterol homeostasis. Disruption of the Pex2 gene leads to peroxisome deficiency and widespread metabolic dysfunction. The Pex2(-/-) mouse model for Zellweger syndrome enabled us to evaluate the role of peroxisomes in cholesterol biosynthesis. These studies have shown that Pex2(-/-) mice exhibit low levels of cholesterol in plasma and liver. Pex2(-/-) mice were unable to maintain normal cholesterol homeostasis despite activation of SREBP-2, the master transcriptional regulator of cholesterol biosynthesis, and increased protein levels and activities of cholesterol biosynthetic enzymes. The SREBP-2 pathway remained activated even after normalization of hepatic cholesterol levels in response to bile acid feeding as well as in extrahepatic tissues and the liver of neonatal and longer surviving Pex2 mutants, where cholesterol levels were normal. Several studies have shown that endoplasmic reticulum (ER) stress can dysregulate lipid metabolism via SREBP activation independently of intracellular cholesterol concentration. We demonstrated that peroxisome deficiency activates endoplasmic reticulum stress pathways in Pex2(-/-) mice, especially the integrated stress response mediated by PERK and ATF4 signaling, and thereby leads to dysregulation of the SREBP-2 pathway. Our findings suggest that functional peroxisomes are necessary to prevent chronic ER stress and dysregulation of the endogenous sterol response pathway. The constitutive activation of ER stress pathways might contribute to organ pathology and metabolic dysfunction in peroxisomal disorder patients. Copyright © 2013 Elsevier Masson SAS. All rights
Perdian, D.C.; Cha, Sangwon; Oh, Jisun; Sakaguchi, Donald S.; Yeung, Edward S.; and Lee, Young Jin
Mass spectrometric imaging has been utilized to localize individual astrocytes and to obtain cholesterol populations at the single-cell level in laser desorption ionization (LDI) with colloidal silver. The silver ion adduct of membrane-bound cholesterol was monitored to detect individual cells. Good correlation between mass spectrometric and optical images at different cell densities indicates the ability to perform single-cell studies of cholesterol abundance. The feasibility of quantification is confirmed by the agreement between the LDI-MS ion signals and the results from a traditional enzymatic fluorometric assay. We propose that this approach could be an effective tool to study chemical populations at the cellular level.
Perdian, D C; Cha, Sangwon; Oh, Jisun; Sakaguchi, Donald S; Yeung, Edward S; Lee, Young Jin
Mass spectrometric imaging has been utilized to localize individual astrocytes and to obtain cholesterol populations at the single-cell level in laser desorption ionization (LDI) with colloidal silver. The silver ion adduct of membrane-bound cholesterol was monitored to detect individual cells. Good correlation between mass spectrometric and optical images at different cell densities indicates the ability to perform single-cell studies of cholesterol abundance. The feasibility of quantification is confirmed by the agreement between the LDI-MS ion signals and the results from a traditional enzymatic fluorometric assay. We propose that this approach could be an effective tool to study chemical populations at the cellular level.
Wysokiński, Adam; Strzelecki, Dominik; Kłoszewska, Iwona
The aim of this study is to investigate differences in triglycerides (TGA), cholesterol (TC), HDL, LDL and glucose (FPG) levels in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Results for 2305 Caucasian patients were included in the study (1377 women, 59.7%; mean age 45.6). Mean TGA level was: schizophrenia: 139.9±90.6 mg/dL, unipolar depression: 125.4±70.8 mg/dL, bipolar disorder: 141.1±81.9 mg/dL, bipolar depression: 147.7±82.8 mg/dL mg/dL, bipolar mania: 120.2±76.1 mg/dL, inter-group differences were significant (p<0.001). Mean TC level was: schizophrenia: 188.5±40.4 mg/dL, unipolar depression: 198.8±50.7 mg/dL, bipolar disorder: 194.4±48.3 mg/dL, bipolar depression: 198.9±48.8 mg/dL, bipolar mania: 180.1±43.8 mg/dL, inter-group differences were significant (p<0.001). Mean HDL level was: schizophrenia: 45.3±13.9 mg/dL, unipolar depression: 48.1±14.8 mg/dL, bipolar disorder: 45.4±15.3 mg/dL, bipolar depression: 45.1±15.4 mg/dL, bipolar mania: 46.4±15.1 mg/dL, inter-group differences were significant (p<0.001). Mean LDL level was: schizophrenia: 115.4±34.7 mg/dL, unipolar depression: 125.7±44.1 mg/dL, bipolar disorder: 120.9±42.1 mg/dL, bipolar depression: 124.5±43.1 mg/dL, bipolar mania: 109.3±36.9 mg/dL, inter-group differences were significant (p<0.001). Mean FPG level was: schizophrenia: 95.9±24.9 mg/dL, unipolar depression: 94.8±22.9 mg/dL, bipolar disorder: 97.2±24.4 mg/dL, bipolar depression: 98.3±25.3 mg/dL, bipolar mania: 93.9±21.1 mg/dL, inter-group differences were not significant (p=0.08). Odds ratios for glucose and lipids abnormalities, correlations with age, sex distribution in diagnostic groups for normal ranges of glucose and lipids, differences in glucose and lipids levels between the age groups were also calculated. Our results confirm that there is a high prevalence of lipid and glucose abnormalities in patients with schizophrenia and mood disorders (both unipolar and
Goodman, D.S.; Deckelbaum, R.J.; Palmer, R.H.; Dell, R.B.; Ramakrishnan, R.; Delpre, G.; Beigel, Y.; Cooper, M.
Total body turnover of cholesterol was studied in two patients with abetalipoproteinemia, a 32-year-old man and a 31-year-old woman. The patients received (14C)cholesterol intravenously, and the resulting specific activity-time curves (for 40 and 30 weeks, respectively) were fitted with a three-pool model. Parameters were compared with those from studies of cholesterol turnover in 82 normal and hyperlipidemic subjects. A three-pool model gave the best fit for the abetalipoproteinemic patients, as well as for the 82 previously studied subjects, suggesting general applicability of this model. Cholesterol production rates in the two abetalipoproteinemic subjects (0.82 and 0.89 g/day) were close to values predicted for persons of their body weight. Thus, total body turnover rate of cholesterol was quite normal in abetalipoproteinemia, confirming previous reports. Very low values (9.2 and 8.4 g) were found for M1, the size of the rapidly exchanging compartment pool 1, in the two abetalipoproteinemic subjects. These values were well below the values predicted (from the comparison study population) for normal persons of this size with low plasma cholesterol levels. For one patient, total body exchangeable cholesterol was very low, although not significantly below the predicted values for a person of his size. In the second patient, the observed estimate for total body exchangeable cholesterol was well within the range of values predicted for persons of her size with low to extremely low cholesterol levels.
Rosenthal, M B; Barnard, R J; Rose, D P; Inkeles, S; Hall, J; Pritikin, N
Recent studies have implicated elevated levels of serum estradiol in males as the major predisposing factor for myocardial infarction, with serum cholesterol playing a secondary role. The purpose of the present study was to investigate the effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet and daily exercise on levels of serum estradiol, testosterone, and lipids in males. Twenty-one males participating in the Pritikin Longevity Center 26-day residential program volunteered for the study. During the program, serum estradiol levels were significantly reduced from 47.2 +/- 4.6 to 23.8 +/- 2.5 pg/ml (mean +/- SE) whereas serum testosterone levels were unchanged (5.1 +/- 0.3 versus 5.1 +/- 0.2 ng/ml). Total serum cholesterol levels were reduced from 229 +/- 9 to 181 +/- 7 mg/dl whereas triglyceride levels were reduced from 301 +/- 66 to 151 +/- 13 mg/dl. High-density lipoprotein-cholesterol levels fell from 41 +/- 3 to 35 +/- 1 mg/dl whereas the ratio of total cholesterol to high-density lipoprotein-cholesterol was unchanged (5.5 +/- 0.4 versus 5.1 +/- 0.3).
Choi, I H; Park, W Y; Kim, Y J
This study was carried out to evaluate the effects of supplementing diets with garlic powder and alpha-tocopherol on performance, serum cholesterol levels, and meat quality of chickens. Three hundred 1-d-old male broiler chicks were assigned to 5 diet treatments (0, 1, 3, and 5% garlic powder and 3% garlic powder + 200 IU of alpha-tocopherol/kg) with 3 replications of 20 birds for 35 d. There were no significant differences in broiler performance among the treatments. Moisture and crude ash contents of chicken thigh muscle were not different among all treatments, but dietary garlic powder and alpha-tocopherol supplementation resulted in significantly higher CP and lower crude fat contents in comparison with control (P < 0.05). Increasing the levels of garlic powder and applying garlic powder plus alpha-tocopherol significantly decreased total and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol in broiler blood (P < 0.05). The pH and TBA reactive substances values were significantly reduced (P < 0.05) by the inclusion of garlic powder and alpha-tocopherol. However, no significant differences in water-holding capacity or shear force values were observed among the treatments. For broiler thigh muscle color, L* (lightness) values were decreased (P < 0.05), and a* (redness) and b* (yellowness) values were increased (P < 0.05) with the increased garlic powder levels and the combination of garlic powder and alpha-tocopherol. In terms of fatty acid composition in thigh muscle, unlike saturated fatty acid and total saturated fatty acid, dietary garlic powder or garlic powder plus alpha-tocopherol supplementation increased unsaturated fatty acid, total unsaturated fatty acid, and total unsaturated fatty acid:total saturated fatty acid ratios. These results suggest that 5% garlic powder or 3% garlic powder plus 200 IU of alpha-tocopherol antioxidant properties were effective for enhancing lipid and color stability.
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
Makarchikov, Alexander F; Wins, Pierre; Janssen, Edwin; Wieringa, Bé; Grisar, Thierry; Bettendorff, Lucien
Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues and it may act as a phosphate donor for the phosphorylation of proteins, suggesting a potential role in cell signaling. Two mechanisms have been proposed for the enzymatic synthesis of ThTP. A thiamine diphosphate (ThDP) kinase (ThDP+ATP if ThTP+ADP) has been purified from brewer's yeast and shown to exist in rat liver. However, other data suggest that, at least in skeletal muscle, adenylate kinase 1 (AK1) is responsible for ThTP synthesis. In this study, we show that AK1 knockout mice have normal ThTP levels in skeletal muscle, heart, brain, liver and kidney, demonstrating that AK1 is not responsible for ThTP synthesis in those tissues. We predict that the high ThTP content of particular tissues like the Electrophorus electricus electric organ, or pig and chicken skeletal muscle is more tightly correlated with high ThDP kinase activity or low soluble ThTPase activity than with non-stringent substrate specificity and high activity of adenylate kinase.
Ahmed, Haitham M; Miller, Michael; Nasir, Khurram; McEvoy, John W; Herrington, David; Blumenthal, Roger S; Blaha, Michael J
Prior studies observing associations between low levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease (CVD) have often been conducted among persons with metabolic or other lipid abnormalities. In this study, we investigated the association between primary low HDL cholesterol and coronary heart disease (CHD), CVD, and all-cause death after adjustment for confounders in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants who were free of clinical CVD were recruited from 6 US research centers from 2000 to 2002 and followed for a median duration of 10.2 years. We defined "primary low HDL cholesterol" as HDL cholesterol level <40 mg/dL (men) or <50 mg/dL (women), triglyceride level <100 mg/dL, and low-density lipoprotein cholesterol level <100 mg/dL (n = 158). We defined an "optimal" lipid profile as HDL cholesterol ≥40 mg/dL (men) or ≥50 mg/dL (women) and triglycerides and low-density lipoprotein cholesterol <100 mg/dL (n = 780). For participants with primary low HDL cholesterol versus those with an optimal lipid profile, adjusted hazard ratios for total CHD, CVD, and death were 2.25 (95% confidence interval (CI): 1.20, 4.21; P = 0.011), 1.93 (95% CI: 1.11, 3.34; P = 0.020), and 1.11 (95% CI: 0.67, 1.84; P = 0.69), respectively. Participants with primary low HDL cholesterol had higher risks of CHD and CVD than participants with optimal lipid profiles but no difference in survival after a median 10.2 years of follow-up. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: email@example.com.
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
Kanda, Eiichiro; Ai, Masumi; Iwamoto, Asami; Okazaki, Mitsuyo; Maeda, Yoshitaka; Sasaki, Sei; Yoshida, Masayuki
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. 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). 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). 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.
Adorni, M. P.; Zimetti, F.; Puntoni, M.; Bigazzi, F.; Sbrana, F.; Minichilli, F.; Bernini, F.; Ronda, N.; Favari, E.; Sampietro, T.
High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to reduce LDL-C levels, has been shown to also affect HDL levels and composition. We studied LDL-apheresis effects on six FH and nine FCH subjects’ serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. The procedure reduced total cholesterol (TC), LDL-C, and apoB plasma levels (−69%, −80% and −74%, respectively), parameters only partially restored two days later. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (−27% and −16%, respectively), were restored to almost normal levels two days later. LDL-apheresis reduced serum aqueous diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored whereas ABCA1-CEC remained low two days later. Sera immediately and two days after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion, LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces also serum capacity to deliver cholesterol to macrophages. Despite a potentially negative effect on HDL levels and composition, LDL-apheresis may counteract foam cells formation. PMID:22414482
Proitsi, Petroula; Lupton, Michelle K; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F
Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Genetic predisposition to increased blood cholesterol and triglyceride
Proitsi, Petroula; Lupton, Michelle K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F.
Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n = 10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10−8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10−8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR] = 1.005, 95% CI 0.82–1.24, p = 0.962 per 1 unit increase in HDL-c; OR = 0.901, 95% CI 0.65–1.25, p = 0.530 per 1 unit increase in LDL-c; OR = 1.104, 95% CI 0.89–1.37, p = 0.362 per 1 unit increase in triglycerides; and OR = 0.954, 95% CI 0.76–1.21, p = 0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller
de Munter, Wouter; van der Kraan, Peter M; van den Berg, Wim B; van Lent, Peter L E M
There is increasing evidence that low-density lipoprotein (LDL) cholesterol plays a role in the pathology of OA. Specifically, oxidized LDL (oxLDL), which has been shown to play an essential role during development of atherosclerosis, could be involved in processes such as synovial inflammation, cartilage destruction and bone deformations. OxLDL can activate synovial cells such as macrophages, endothelial cells and synovial fibroblasts, resulting in release of growth factors, MMP and pro-inflammatory cytokines. In this review article, we discuss the role of LDL and oxLDL in OA joint pathology and share our viewpoint of possible mechanisms by which these proteins could influence the development and progression of OA. The proposed theory could provide insight into the aetiopathology of OA and give rise to new potential treatments.
Vella, Sandro; Bezzina Sultana, Maureen; Fava, Stephen
We investigated the hypotheses that mean population body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and the prevalence of type 2 diabetes (T2DM) are correlated with type 1 diabetes (T1DM) incidence rates. Population-based mean incidence rates for T1DM in children aged ≤14 years participating in the World Health Organization Diabetes Mondial (DiaMond) project were compared with population mean values for BMI, SBP, TC and FPG, as well as prevalence rates for T2DM as reported by The Global Burden of Metabolic Risk Factors Chronic Diseases Collaborating Group, using Spearman's rank correlation and multiple regression analysis. The mean incidence rate for T1DM in boys was significantly correlated with country mean BMI, SBP and TC in men and mean TC in women, and negatively correlated with the country incidence of T2DM in either gender. We also found significant correlations between mean incidence rates of T1DM in girls and mean BMI, SBP and TC in men and mean TC in women. In multiple regression analyses, mean TC emerged as the sole significant predictor for T1DM in both boys (P < 0.001, adjusted R2 = 0.393) and girls (P < 0.001, adjusted R2 = 0.372). Population mean total cholesterol is a significant predictor for country incidence of type 1 diabetes in both boys and girls. This association may fuel the rising incidence rates of type 1 diabetes reported in many countries.
Calan, Ozlem Gursoy; Akan, Pinar; Cataler, Aysenur; Dogan, Cumhur; Kocturk, Semra
Increased amyloid beta (AB) peptide concentration is one of the initiating factors in the neurodegeneration process. It has been suggested that cholesterol induces the synthesis of AB peptide from amyloid precursor protein or facilitates the formation of amyloid plaque by lowering the aggregation threshold of the peptide. It is also shown that AB peptides may affect cholesterol metabolism and the synthesis of steroid hormones such as progesterone and estradiol. Pregnenolone (P) and pregnenolone sulfate (PS) are the major steroids produced from cholesterol in neural tissue. In toxicity conditions, the effect of AB peptides on P and PS levels has not yet been determined. Furthermore, it has not been clearly defined how changes in cellular P and PS levels affect neuronal cell survival. The aim of this study was to determine the effects of AB peptides on cellular changes in P and PS levels depending on the level of their main precursor, cholesterol. Cholesterol and toxic concentrations of AB fragments (AB 25-35, AB 1-40 and AB 1-42) were applied to PC-12 and SH-SY5Y cells. Changes in cellular cholesterol, P and PS levels were determined simultaneously in a dose-and time-dependent manner. The cell viability and cell death types were also evaluated. AB peptides affected both cell viability and P/PS levels. Steroid levels were altered depending on AB fragment type and the cholesterol content of the cells. Treatment with each of the AB fragments alone increased P levels by twofold. However, combined treatment with AB peptides and cholesterol increased P levels by approximately sixfold, while PS levels were increased only about 2.5 fold in both cell lines. P levels in the groups treated with AB 25-35 were higher than those in AB 1-40 and AB 1-42 groups. The cell viabilities were significantly low in the group treated by AB and cholesterol (9 mM). The effect of AB peptides on P levels might be a result of cellular self-defense. On the other hand, the rate of P increase
Ebuehi, O A T; Ajuluchukwu, A E; Afolabi, O T; Ebuehi, O M; Akinwande, A I
Diabetes mellitus is a disorder of carbohydrate metabolism and is associated with oxidative reactions. The present study is to determine the activities of catalase, lipid peroxidation, glucose, protein, cholesterol and triglyceride concentrations in the liver and kidney in alloxan-induced diabetes in female and male rats. In addition, the study is to ascertain if gender differences affect oxidative stress in diabetes. Forty male (165 +/- 8.46 g) and female (162.7 +/- 7.94 g) albino Sprague Dawley rats were used for the study. The rats were injected intraperitoneally with a single dose of 150 mg/body weight of alloxan monohydrate, to induce diabetes-for 14 days. The rats were divided into four groups, consisting of 10 diabetic male, 10 non-diabetic male, 10 diabetic female and 10 non-diabetic female. The rats were fed rat chow and water ad libitum for 14 days and then sacrificed by decapitation. Blood was taken by cardiac puncture, while liver and kidney were quickly excised. The catalase activity, lipid peroxidation, glucose, protein, cholesterol and triglyceride concentrations in the liver and kidney of rats were determined. Bats administered alloxan monohydrate had elevated plasma glucose levels. The body weights of diabetic female and male rats were significantly reduced compared to the non-diabetic rats. The catalase activities in liver and kidney of diabetic male or female rats were significantly lower than in non-diabetic rats but the reduction was more pronounced in diabetic female rats. The liver lipid peroxidation, cholesterol and triglyceride levels were significantly higher in the diabetic male or female than in the non-diabetic rats, but with no significant differences in the diabetic female or male rats. Data of the study indicate that sex differences do not significantly affect oxidative stress in alloxan-induced diabetes mellitus.
Satoh, Michihiro; Ohkubo, Takayoshi; Asayama, Kei; Murakami, Yoshitaka; Sakurai, Masaru; Nakagawa, Hideaki; Iso, Hiroyasu; Okayama, Akira; Miura, Katsuyuki; Imai, Yutaka; Ueshima, Hirotsugu; Okamura, Tomonori
No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population. © 2015 American Heart Association, Inc.
Eggertsen, Robert; Andreasson, Åke; Andrén, Lennart
Objective To assess the effect of treatment with a St John's Wort product (Movina®) on cholesterol levels (total cholesterol, LDL-cholesterol, and HDL-cholesterol) in patients with hypercholesterolemia on treatment with a stable dose of simvastatin. Design Controlled, randomized, open, crossover pharmacodynamic study. Setting Two primary healthcare centres. Intervention Patients were treated with Movina® one tablet (containing 300 mg of Hypericum perforatum) twice daily and control (a commercially available multivitamin tablet, Vitamineral®). The trial started with a run-in period of 4 weeks. Then the treatment order between control and active treatment was decided (randomization using sealed envelopes). The duration of each treatment period was 4 weeks and simvastatin treatment was kept unchanged during the whole study period (12 weeks). Subjects Twenty-four patients with hypercholesterolemia treated with a stable dose of simvastatin (10–40 mg daily) for at least three months. Main outcome measures Assessments of total cholesterol, HDL- cholesterol, LDL-cholesterol, and triglycerides were performed in the morning with the patients in a fasting condition. Results All patients completed the study. LDL-cholesterol was significantly increased during active treatment compared with control. Thus, the mean LDL-cholesterol after 4 weeks’ active treatment was 2.72 mmol/L compared with 2.30 mmol/L after treatment with control (p <0.0001). An increase in total-cholesterol was also observed (5.08 mmol/L compared with 4.56 mmol/L, p <0.0001). Conclusion Products containing St John's Wort should not be given to patients with hypercholesterolemia who are on treatment with simvastatin. PMID:17846933
Fang, Longhou; Choi, Soo-Ho; Baek, Ji Sun; Liu, Chao; Almazan, Felicidad; Ulrich, Florian; Wiesner, Philipp; Taleb, Adam; Deer, Elena; Pattison, Jennifer; Torres-Vázquez, Jesús; Li, Andrew C.; Miller, Yury I.
Cholesterol is a structural component of the cell, indispensable for normal cellular function, but its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (ApoA-I) and to the ApoA-I-containing high-density lipoprotein (HDL)1-3. Maintaining efficient cholesterol efflux is essential for normal cellular function4-6. However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that ApoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells (EC) to HDL and thereby regulates angiogenesis. AIBP/HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 dimerization and signaling, and inhibits VEGF-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Remarkably, Aibp regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell autonomous regulator of zebrafish angiogenesis. Aibp knockdown results in dysregulated sprouting/branching angiogenesis, while forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1/Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1/Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from EC and that effective cholesterol efflux is critical for proper angiogenesis. PMID:23719382
Methyl protodioscin increases ABCA1 expression and cholesterol efflux while inhibiting gene expressions for synthesis of cholesterol and triglycerides by suppressing SREBP transcription and microRNA 33a/b levels.
Ma, Weilie; Ding, Hang; Gong, Xiaohua; Liu, Zhen; Lin, Yalin; Zhang, Zhizhen; Lin, Guorong
Sterol regulatory element-binding proteins (SREBPs) regulate homeostasis of LDL, HDL and triglycerides. This study was aimed to determine if inhibition of SREBPs by methyl protodioscin (MPD) regulates downstream gene and protein expressions of lipid metabolisms. In THP-1 macrophages, MPD increases levels of ABCA1 mRNA and protein in dose- and time-dependent manners, and apoA-1-mediated cholesterol efflux. The underlying mechanisms for the effects is that MPD inhibits the transcription of SREBP1c and SREBP2, and decreases levels of microRNA 33a/b hosted in the introns of SREBPs, which leads to reciprocally increase ABCA1 levels. In HepG2 cells, MPD shows the same effects as these observed in THP-1 macrophages. MPD also decreases the gene expressions of HMGCR, FAS and ACC for cholesterol and fatty acid synthesis. MPD further promotes LDL receptor through reducing the PCSK9 level. Collectively, the study demonstrates that MPD potentially increase HDL cholesterol while reducing LDL cholesterol and triglycerides. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Hong, Sun Hee; Kim, Mijeong; Woo, Minji
BACKGROUND/OBJECTIVES Owing to health concerns related to the consumption of traditional snacks high in sugars and fats, much effort has been made to develop functional snacks with low calorie content. In this study, a new recipe for Korean rice cookie, dasik, was developed and its antioxidative, lipid-lowering, and anti-inflammatory effects and related mechanisms were elucidated. The effects were compared with those of traditional rice cake dasik (RCD), the lipid-lowering effect of which is greater than that of traditional western-style cookies. MATERIALS/METHODS Ginseng-added brown rice dasik (GBRD) was prepared with brown rice flour, fructooligosaccharide, red ginseng extract, and propolis. Mice were grouped (n = 7 per group) into those fed a normal AIN-76 diet, a high-fat diet (HFD), and HFD supplemented with RCD or GBRD. Dasik in the HFD accounted for 7% of the total calories. The lipid, reactive oxygen species, and peroxynitrite levels, and degree of lipid peroxidation in the plasma or liver were determined. The expression levels of proteins involved in lipid metabolism and inflammation, and those of antioxidant enzymes were determined by western blot analysis. RESULTS The plasma and hepatic total cholesterol concentrations in the GBRD group were significantly decreased via downregulation of sterol regulatory element-binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (P < 0.05). The hepatic peroxynitrite level was significantly lower, whereas glutathione was higher, in the GBRD group than in the RCD group. Among the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were significantly upregulated in the GBRD group (P < 0.05). In addition, nuclear factor-kappaB (NF-κB) expression in the GBRD group was significantly lower than that in the RCD group. CONCLUSIONS GBRD decreases the plasma and hepatic cholesterol levels by downregulating cholesterol synthesis. This new dasik recipe also improves the antioxidative and anti
Jayashankar, C A; Andrews, Henley Punnen; Vijayasarathi; Pinnelli, Venkata BharatKumar; Shashidharan, Basappaji; Nithin Kumar, H N; Vemulapalli, Swaapnika
We aimed to identify the predictors of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (type 2 DM). About fifty Asian Indian patients with type 2 DM patients aged >40 years and fifty sex- and age-matched nondiabetic controls were enrolled for this study. Following complete medical history and baseline clinical data, laboratory investigations were performed to assess fasting and postprandial plasma glucose levels, lipid profile, blood urea, serum creatinine, and serum uric acid levels. Body mass index (BMI), waist-to-hip ratio, serum uric acid, serum total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, very LDL cholesterol were significantly higher among diabetic patients compared to controls. On univariate analysis, serum LDL cholesterol (odds ratio [OR]: 29.67, P < 0.001), serum uric acid (OR: 25.65, P < 0.001), low high-density lipoprotein (HDL) cholesterol (OR: 21.12, P < 0.001), hypertension (OR: 17.06, P < 0.001), family history of cardiovascular disease (CVD) (OR: 9.43, P = 0.002), and duration of diabetes (OR: 4.65, P = 0.03) were identified as predictors of CVD among diabetic patients. On multivariate regression, only LDL cholesterol (OR: 1.51, P = 0.002) and serum uric acid (OR: 1.21, P = 0.01) were the independent predictors of CAD among diabetic patients. Significant positive correlation of serum uric acid with duration of diabetes (r = 0.38, P = 0.006), BMI (r = 0.35, P = 0.01), triglycerides (r = 0.356, P = 0.01), LDL cholesterol (r = 0.38, P = 0.007), HDL cholesterol (r = -0.514, P < 0.001), and hypertension (r = 0.524, P < 0.001) was observed. Serum LDL cholesterol and hyperuricemia may serve as independent predictors of CAD among Asian Indian subjects with type 2 DM.
Wei, Hao; Tarling, Elizabeth J; McMillen, Timothy S; Tang, Chongren; LeBoeuf, Renée C
In addition to triacylglycerols, adipocytes contain a large reserve of unesterified cholesterol. During adipocyte lipolysis and cell death seen during severe obesity and weight loss, free fatty acids and cholesterol become available for uptake and processing by adipose tissue macrophages (ATMs). We hypothesize that ATMs become cholesterol enriched and participate in cholesterol clearance from adipose tissue. We previously showed that ABCG1 is robustly upregulated in ATMs taken from obese mice and further enhanced by caloric restriction. Here, we found that ATMs taken from obese and calorie-restricted mice derived from transplantation of WT or Abcg1-deficient bone marrow are cholesterol enriched. ABCG1 levels regulate the ratio of classically activated (M1) to alternatively activated (M2) ATMs and their cellular cholesterol content. Using WT and Abcg1(-/-) cultured macrophages, we found that Abcg1 is most highly expressed by M2 macrophages and that ABCG1 deficiency is sufficient to retard macrophage chemotaxis. However, changes in myeloid expression of Abcg1 did not protect mice from obesity or impaired glucose homeostasis. Overall, ABCG1 modulates ATM cholesterol content in obesity and weight loss regimes leading to an alteration in M1 to M2 ratio that we suggest is due to the extent of macrophage egress from adipose tissue.
Zhao, Qin; Li, Jianfei; Yang, Jin; Li, Rongshan
The aim of the study was to evaluate associations of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels with prognosis in coronary heart disease (CHD) patients with heart failure (HF).Patients who were angiographical-diagnosis of CHD and echocardiographical-diagnosis of left ventricular ejection fraction (LVEF) < 45% were enrolled. Baseline characteristics were collected and association of TC and HDL-C levels with rehospitalization for HF and all-cause mortality was assessed.A total of 118 patients were recruited. Mean age was 58.6 ± 10.9 years and male accounted for 65%. Mean LVEF was 39.5 ± 4.0%. Twenty-eight patients were rehospitalized for HF and 6 patients were dead. In patients with poor prognosis, lower body mass index (BMI), TC, HDL-C and albumin while higher high sensitivity C-reactive protein (Hs-CRP) was observed. TC was positively correlated with BMI and albumin, and HDL-C was inversely correlated with Hs-CRP. The associations of TC level and rehospitalization for HF and all-cause mortality were attenuated but consistently significant through model 1 to 4, with odds ratio (OR) of 0.97 (95% confidence interval [CI]: 0.92-0.99). Associations of HDL-C level and rehospitalization for HF and all-cause mortality were also consistently significant through model 1 to 4, with OR of 0.95 (95% CI: 0.90-0.98). Strength of association was attenuated prominently in model 3 after adjusted for Hs-CRP, and no change was observed after further adjusted for BMI and albumin.Higher baseline TC and HDL-C levels are associated with better outcome in CHD patients with HF.
Zhao, Qin; Li, Jianfei; Yang, Jin; Li, Rongshan
Abstract The aim of the study was to evaluate associations of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels with prognosis in coronary heart disease (CHD) patients with heart failure (HF). Patients who were angiographical-diagnosis of CHD and echocardiographical-diagnosis of left ventricular ejection fraction (LVEF) < 45% were enrolled. Baseline characteristics were collected and association of TC and HDL-C levels with rehospitalization for HF and all-cause mortality was assessed. A total of 118 patients were recruited. Mean age was 58.6 ± 10.9 years and male accounted for 65%. Mean LVEF was 39.5 ± 4.0%. Twenty-eight patients were rehospitalized for HF and 6 patients were dead. In patients with poor prognosis, lower body mass index (BMI), TC, HDL-C and albumin while higher high sensitivity C-reactive protein (Hs-CRP) was observed. TC was positively correlated with BMI and albumin, and HDL-C was inversely correlated with Hs-CRP. The associations of TC level and rehospitalization for HF and all-cause mortality were attenuated but consistently significant through model 1 to 4, with odds ratio (OR) of 0.97 (95% confidence interval [CI]: 0.92–0.99). Associations of HDL-C level and rehospitalization for HF and all-cause mortality were also consistently significant through model 1 to 4, with OR of 0.95 (95% CI: 0.90–0.98). Strength of association was attenuated prominently in model 3 after adjusted for Hs-CRP, and no change was observed after further adjusted for BMI and albumin. Higher baseline TC and HDL-C levels are associated with better outcome in CHD patients with HF. PMID:28248864
Dávalos, Alberto; Fernández-Hernando, Carlos
There has been strong evolutionary pressure to ensure that an animal cell maintain levels of cholesterol within tight limits for normal function. Imbalances in cellular cholesterol levels are a major player in the development of different pathologies associated to dietary excess. Although epidemiological studies indicate that elevated levels of high-density lipoprotein (HDL)-cholesterol reduce the risk of cardiovascular disease, recent genetic evidence and pharmacological therapies to raise HDL levels do not support their beneficial effects. Cholesterol efflux as the first and probably the most important step in reverse cholesterol transport is an important biological process relevant to HDL function. Small non-coding RNAs (microRNAs), post-transcriptional control different aspects of cellular cholesterol homeostasis including cholesterol efflux. miRNA families miR-33, miR-758, miR-10b, miR-26 and miR-106b directly modulates cholesterol efflux by targeting the ATP-binding cassette transporter A1 (ABCA1). Pre-clinical studies with anti-miR therapies to inhibit some of these miRNAs have increased cellular cholesterol efflux, reverse cholesterol transport and reduce pathologies associated to dyslipidemia. Although miRNAs as therapy have benefits from existing antisense technology, different obstacles need to be solved before we incorporate such research into clinical care. Here we focus on the clinical potential of miRNAs as therapeutic target to increase cholesterol efflux and reverse cholesterol transport as a new alternative to ameliorate cholesterol-related pathologies. PMID:23435093
The importance of equipment noise normalization in the complex of measures aimed at reducing noise in work spaces, as well as the necessity of correlating these norms with the criteria that establish the noxious values of noise for man are outlined.
Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...
Krycer, James Robert; Brown, Andrew John
Prostate cancer (PCa) is the most common cancer in men in developed countries. Epidemiological studies have associated high blood-cholesterol levels with an increased risk of PCa, whilst cholesterol-lowering drugs (statins) reduce the risk of advanced PCa. Furthermore, normal prostate epithelial cells have an abnormally high cholesterol content, with cholesterol levels increasing further during progression to PCa. In this review, we explore why and how this occurs. Concurrent to this observation, intense efforts have been expended in cardiovascular research to better understand the regulators of cholesterol homeostasis. Here, we apply this knowledge to elucidate the molecular mechanisms driving the accumulation of cholesterol in PCa. For instance, recent evidence from our group and others shows that major signalling players in prostate growth and differentiation, such as androgens and Akt, modulate the key transcriptional regulators of cholesterol homeostasis to enhance cholesterol levels. This includes adjusting central carbon metabolism to sustain greater lipid synthesis. Perturbations in cholesterol homeostasis appear to be maintained even when PCa approaches the advanced, 'castration-resistant' state. Overall, this provides a link between cholesterol accumulation and PCa cell growth. Given there is currently no cure for castration-resistant PCa, could cholesterol metabolism be a novel target for PCa therapy? Overall, this review presents a picture that cholesterol metabolism is important for PCa development: growth-promoting factors stimulate cholesterol accumulation, which in turn presents a possible target for chemotherapy. Consequently, we recommend future investigations, both to better elucidate the mechanisms driving this accumulation and applying it in novel chemotherapeutic strategies.
Deser, Serkan Burc; Bayoglu, Burcu; Besirli, Kazım; Cengiz, Mujgan; Arapi, Berk; Junusbekov, Yerik; Dirican, Ahmet; Arslan, Caner
Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.
van Tienhoven-Wind, L J N; Dallinga-Thie, G M; Dullaart, R P F
Low-normal thyroid function within the euthyroid range may confer higher plasma triglycerides, but relationships with plasma apolipoprotein (apo) E, which plays an important role in the metabolism of triglyceride-rich apoB-containing lipoproteins, are unknown. We determined relationships of plasma apoE with thyroid stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects with and without Type 2 diabetes mellitus (T2DM). TSH, free T4, lipids, and apoE were measured in fasting plasma from 72 T2DM subjects and 82 nondiabetic subjects. The APOE genotype was also determined. Free T4 was slightly higher in T2DM (p=0.030), but TSH levels were not different vs. nondiabetic subjects. The APOE genotype distribution was not different between the groups. None of the participants had the ε2/ε2 genotype. Plasma triglycerides were higher in T2DM (p=0.037). ApoB and apoE levels were not different between the groups. In all subjects combined, multivariable analysis showed that plasma triglycerides (p=0.039), non-high density lipoprotein (non-HDL) cholesterol (p=0.030), and apoE levels (p=0.002) were each independently and positively associated with TSH after adjustment for age, sex, T2DM and the presence of the APOE ε3 allele. Furthermore, the associations of TSH with apoE remained present after adjustment for either triglycerides, non-HDL cholesterol, or apoB (p=0.005 to 0.023). The presence of T2DM did not modify the relationships of TSH with these (apo) lipoprotein variables (p=0.11 to 0.36). In conclusion, low-normal thyroid function, as indicated by higher TSH levels within the euthyroid range, may influence the metabolism of triglyceride-rich lipoproteins by affecting apoE regulation. © Georg Thieme Verlag KG Stuttgart · New York.
Hyperlipidemia - cholesterol and lifestyle; CAD - cholesterol and lifestyle; Coronary artery disease - cholesterol and lifestyle; Heart disease - cholesterol and lifestyle; Prevention - cholesterol and lifestyle; Cardiovascular disease - ...
Abulhul, Esam; McDonald, Kenneth; Martos, Ramon; Phelan, Dermot; Spiers, J Paul; Hennessy, Martina; Baugh, John; Watson, Chris; O'Loughlin, Christina; Ledwidge, Mark
The role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP. This study determined whether there was an increase in serum markers of inflammation, fibrosis (including PIIINP), and B-type natriuretic peptide (BNP) in patients with systolic HF and normal total cholesterol and determined the effects of long-term treatment with atorvastatin on these markers. Fifty-six white patients with systolic HF and normal cholesterol levels (age 72  years; 68% male; body mass index 27.0 [7.3] kg/m(2); ejection fraction 35 %; 46% with history of smoking) were randomly allocated to atorvastatin treatment for 6 months, titrated to 40 mg/d (A group) or not (C group). Age- and/or sex-matched subjects without HF (N group) were also recruited. Biomarkers were measured at baseline (all groups) and 6 months (A and C groups). Serum markers of collagen turnover, inflammation, and BNP were significantly elevated in HF patients compared with normal participants (all P < 0.05). There were correlations between these markers in HF patients but not in normal subjects. Atorvastatin treatment for 6 months caused a significant reduction in the following biomarkers compared with baseline: BNP, from median (interquartile range) 268 (190-441) pg/mL to 185 (144-344) pg/mL; high-sensitivity C-reactive protein (hs-CRP), from 5.26 (1.95 -9.29) mg/L to 3.70 (2.34-6.81) mg/L; and PIIINP, from 4.65 (1.86) to 4.09 (1.25) pg/mL (all P < 0.05 baseline vs 6 months). Between-group differences were significant for PIIINP only (P = 0.027). There was a positive interaction between atorvastatin effects and baseline hs-CRP and PIIINP (P < 0.01). Long-term statin therapy reduced PIIINP in this small, selected HF population with elevated baseline levels. Further evaluation of statin therapy in the management of HF patients with elevated PIIINP is
Greene, Stephen J; Vaduganathan, Muthiah; Lupi, Laura; Ambrosy, Andrew P; Mentz, Robert J; Konstam, Marvin A; Nodari, Savina; Subacius, Haris P; Fonarow, Gregg C; Bonow, Robert O; Gheorghiade, Mihai
Lower cholesterol levels are associated with worse outcomes in patients with chronic heart failure (HF) and have been shown to predict in-hospital mortality. The relation between lipid profile and postdischarge outcomes in patients hospitalized for worsening HF is less clear. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), 3,957 patients hospitalized for worsening HF with ejection fractions ≤40% were examined. Baseline total cholesterol and triglyceride levels were measured <48 hours after admission and evaluated as continuous variables. The primary end points of all-cause mortality and cardiovascular mortality or hospitalization for HF were compared using Cox regression models. Patient characteristics at randomization were also compared among quartiles of total cholesterol. Patients with lower total cholesterol tended to have lower blood pressure, ejection fractions, serum sodium, and albumin, and were more likely to have worse HF functional class, to have higher natriuretic peptide levels, and to have histories of diabetes mellitus, renal insufficiency, and coronary revascularization (all p values <0.001). After adjustment for baseline clinical risk factors, total cholesterol was predictive of all-cause mortality (hazard ratio 0.73, 95% confidence interval 0.63 to 0.85, p <0.001) and cardiovascular mortality or hospitalization for HF (hazard ratio 0.73, 95% confidence interval 0.66 to 0.82, p <0.001) at median follow-up of 9.9 months. Lower baseline triglyceride level was also associated with worse outcomes. In conclusion, lower baseline total cholesterol is correlated with a high-risk patient profile and is a marker of disease severity in patients hospitalized for worsening HF with reduced ejection fraction. Baseline total cholesterol and triglyceride levels are predictive of mortality and HF rehospitalization beyond traditional risk factors. Copyright © 2013 Elsevier Inc. All
Ulloa, Natalia; Arteaga, Eugenio; Bustos, Paulina; Durán-Sandoval, Daniel; Schulze, Kim; Castro, Graciela; Jauhiainen, Matti; Fruchart, Jean Charles; Calvo, Carlos
Thirty healthy postmenopausal women were randomized into 2 groups that received a sequential combined hormone-replacement therapy (HRT) (n = 18; conjugated equine estrogen 0.625 mg/d for 28 days and 5 mg of medroxyprogesterone acetate during the last 14 days) or placebo (n = 12). Plasma samples were collected before and during treatment (days 0, 15, 43, 71). High-density lipoprotein (HDL) lipid content, lipoprotein (Lp)A-I and LpA-I:LpA-II concentration, lecithin:cholesterol acyl transferase activity (LCAT), phospholipid transfer protein (PLTP) activity, and the plasma capacity to carry out cholesterol efflux from Fu5AH cells were measured. Most significant changes were found within the first 15 days after HRT. After 71 days of HRT, we found an increase in LpA-I lipoparticles (27%) and the following HDL lipids: phospholipids (21%), triglycerides (45%), and free cholesterol (43%), as well as an increase in cholesterol efflux (12.5%). PLTP activity, on the other hand, decreased 21% after 71 days of treatment. No significant changes in LCAT activity, HDL-cholesterol ester or LpA-I:LpA-II particles were found. Positive correlation between cholesterol efflux and the variables LpA-I and HDL-phospholipids were observed. PLTP was negatively correlated with apolipoprotein (apo) A-I, LpA-I, and LpA-I:LpA-II. In summary, our study, performed during 3 hormonal cycles, shows that HRT not only modifies HDL-cholesterol level, but also its lipid composition and HDL lipoparticle distribution. HRT enhances the plasma capacity to carry out cholesterol efflux from the Fu5AH system and decreases the activity of PLTP, a key protein regulating HDL levels. Considering the protocol sampling, these results represent mainly the estrogenic effect of HRT.
Cox, C; Mann, J; Sutherland, W; Chisholm, A; Skeaff, M
The physiological effects of coconut oil, butter, and safflower oil on lipids and lipoproteins have been compared in moderately hypercholesterolemic individuals. Twenty eight participants (13 men, 15 women) followed three 6-week experimental diets of similar macronutrient distribution with the different test fats providing 50% total dietary fat. Total cholesterol and low density lipoprotein cholesterol were significantly higher (P < 0.001) on the diet containing butter [6.8 +/- 0.9, 4.5 +/- 0.8 mmol/l] (mean +/- SD), respectively than on the coconut oil diet (6.4 +/- 0.8; 4.2 +/- 0.7 mmol/l) when levels were significantly higher (P < 0.01) than on the safflower diet (6.1 +/- 0.8; 3.9 +/- 0.7 mmol/l). Findings with regard to the other measures of lipids and lipoproteins were less consistent. Apolipoprotein A-I was significantly higher on coconut oil (157 +/- 17 mg/dl) and on butter (141 +/- 23 mg/dl) than on safflower oil (132 +/- 22 mg/dl). Apolipoprotein B was also higher on butter (86 +/- 20 mg/dl) and coconut oil (91 +/- 32 mg/dl) than on safflower oil (77 +/- 19 mg/dl). However gender differences were apparent. In the group as a whole, high density lipoprotein did not differ significantly on the three diets whereas levels in women on the butter and coconut oil diet were significantly higher than on the safflower oil diet. Triacylglycerol was higher on the butter diet than on the safflower and coconut oil diets but the difference only reached statistical significance in women. Cholesteryl ester transfer activity was significantly higher on butter than safflower oil in the group as a whole and in women.(ABSTRACT TRUNCATED AT 250 WORDS)
Background Rheumatoid arthritis (RA) is associated with increased morbidity and mortality from cardiovascular disease (CVD). This can be only partially attributed to traditional CVD risk factors such as dyslipidaemia and their downstream effects on endothelial function. The most common lipid abnormality in RA is reduced levels of high-density lipoprotein (HDL) cholesterol, probably due to active inflammation. In this longitudinal study we hypothesised that anti-tumor necrosis factor-α (anti-TNFα) therapy in patients with active RA improves HDL cholesterol, microvascular and macrovascular endothelial function. Methods Twenty-three RA patients starting on anti-TNFα treatment were assessed for HDL cholesterol level, and endothelial-dependent and -independent function of microvessels and macrovessels at baseline, 2-weeks and 3 months of treatment. Results Disease activity (CRP, fibrinogen, DAS28) significantly decreased during the follow-up period. There was an increase in HDL cholesterol levels at 2 weeks (p < 0.05) which was paralleled by a significant increase in microvascular endothelial-dependent function (p < 0.05). However, both parameters returned towards baseline at 12 weeks. Conclusion Anti-TNFα therapy in RA patients appears to be accompanied by transient but significant improvements in HDL cholesterol levels, which coexists with an improvement in microvascular endothelial-dependent function. PMID:22824166
Bukhari, Shazia A; Rajoka, Muhammad Ibrahim; Ibrahim, Z; Jalal, Fatima; Rana, Shahid Mahboob; Nagra, Saeed A
Maternal oxidative stress during pregnancy may impair fetal growth and help in the development of diseases in adulthood. The aim of current study was to assess total oxidation status (TOS), related parameters and their relationship to DNA damage (%) and homocysteine level in normal pregnant women in low-income participants. In a cross-sectional study healthy women were grouped as normal, while age matched nulliparous and singleton pregnancies were included for first, second and third trimester groups. TOS (P<0.01), melanodialdehyde (MDA) (P<0.001), aspartate aminotransferase (AST) (P<0.01), triiodothyronine (T3) (P<0.01), thyroxine (T4) (P<0.01), and homocysteine (P<0.001), in pregnant women were significantly higher as compared to normal healthy women. While serum total proteins (P<0.01), albumin (P<0.01) and total antioxidant status (TAS) (P<0.001) decreased significantly as compared to normal healthy women. Women in third trimester showed a significantly high level of body temperature (P<0.01), triglyceride (P<0.01), LDL-cholesterol (P<0.05), AST (P<0.01), T3 (P<0.01), homocysteine (P<0.001), TOS (P<0.01) and MDA (P<0.001) but a lower concentration of serum proteins, albumin and TAS at the end of the pregnancy. Pearson correlation indicated a positive relationship of homocysteine with triglycerides (P<0.027), TOS (P<0.01), MDA (P<0.035) and had a negative relationship with total protein (P<0.026). DNA damage was strongly related with T3 (P<0.008), TOS (P<0.02), MDA (P<0.037) and MBI (P<0.048) profiles of pregnant women. These changes were considered normal for pregnant women having optimum blood pressure and normal child birth. Hormonal influences and hemodilution may contribute towards the observed changes in this study.
Three experiments designed to test autistic children's nonverbal and verbal categorization abilities are reported in this paper. In the first two experiments, 14 autistic children were compared to 14 retarded and 14 normal children matched on verbal mental age. Their ability to categorize pictures from basic level categories and from biological and artifactual superordinate level categories was assessed using a matching-to-sample procedure. The three groups of subjects were similar in their performance. Basic level categorization was easier than more abstract categorization, and for all three groups, prototypicality played a role in categorizing superordinate level concepts; that is, children in all three groups made more errors categorizing peripheral examples. In the third experiment, a subgroup of 7 autistic children showed evidence that their lexicons were well organized and that they appreciated the meaning relationships among words at the superordinate level. These findings suggest that autistic children do not suffer a specific cognitive deficit in the ability to categorize and form abstract concepts, as has been previously suggested in the literature.
Olgun, Osman; Yazgan, Oktay; Cufadar, Yusuf
This study was conducted to determine the effects of supplementation of different levels boron and copper on performance, lipids in yolk and plasma contains in layer diets. In this trial a total of 320 layer chicken (26 weeks old age) was randomly distributed in 16 experimental groups. In each experiment group were consist at 5 replicates, and in each replicates there were 4 birds. During the 16 weeks experiment period, birds were fed with 16 experimental diets. Experimental diets were consisting of all possible combination of 4 levels of added boron (0, 60, 120 and 240 mg/kg) and 4 levels of added copper (0, 75, 150 and 300 mg/kg) to the basal ration. Effect of treatments on body weight change and plasma glucose levels were not significant. However, added boron and copper had a significant effect on plasma high-density lipoprotein cholesterol fraction. While added boron had a significant adverse effect on performance parameters, added copper had a significant positive effect on the same parameters. Yolk lipid contents were increased by addition of boron to the ration. However, yolk lipid contents were decreased by addition of copper to the ration. Plasma lipid contents were also decreased by addition of copper and boron in the ration. Results of the present study showed that laying hens from 26 to 42 weeks of age should be fed with 60 mg/kg boron and 150 mg/kg copper supplementation in the diet. Copyright © 2012 Elsevier GmbH. All rights reserved.
Momose, Yuko; Maeda-Yamamoto, Mari; Nabetani, Hiroshi
We conducted a systematic review of the literature for the ability of green tea epigallocatechin gallate (EGCG) to lower low-density lipoprotein cholesterol (LDL-C). Study subjects were limited to healthy individuals and randomized, controlled trials on human serum lipid levels, especially LDL-C, conducted. A total of 17 trials (n = 1356) met all of the inclusion criteria. According to weighted mean differences for changes from baseline with 95% confidence intervals (CI), 107-856 mg/d of EGCG for 4 to 14 weeks reduced LDL-C by -9.29 mg/dl (95% CI, -12.27 to -6.31). Sub-analysis was performed to compare the EGCG lowering effect on LDL-C between non-obese and obese subjects, EGCG dose, baseline of LDL-C levels, or BMI. We concluded that consumption of green tea EGCG resulted in a significant reduction of LDL-C at any baseline level and any dose between 107 and 856 mg/d, and the effect size was slightly dependent on the baseline lipid level of the subjects.
Juren, Andrew J; Sarwal, Gautamn; Al-Sarraf, Ahmad; Vrablik, Michal; Chan, Darren; Humphries, Karin H; Frohlich, Jiri J
Diabetes mellitus and low levels of high-density lipoprotein cholesterol (HDL-C) are among several known risk factors for coronary artery disease. Recent research has shown potential mechanistic links between these two diseases. The aim of our study was to characterize, by examining particular coronary artery disease risk factors, patients with extremely high and low levels of HDL-C who were referred to a prevention clinic. We compared the phenotypes of 113 patients with HDL-C levels greater than the 90th percentile with 212 patients with levels less than the 10th percentile by using a retrospective chart review. The cohort with high HDL-C had a remarkable difference in the incidence of type 2 diabetes (1.8% vs 21.7%). The high HDL-C cohort also had a greater age (52.1 years vs 46.7 years), more light or moderate alcohol consumption (70.8% vs 49.4%), more healthy diet (30.1% vs 22.4%), more light or moderate exercise (90.8% vs 52.2%), and a lower body mass index (25.2 kg/m² vs 28.1 kg/m²). Compared with the low HDL-C group--and also the general population--the high HDL-C cohort had a remarkably low prevalence of diabetes mellitus. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.
Mirmiran, Parvin; Ramezankhani, Azra; Azizi, Fereidoun
This study investigated the combined effect of saturated fat and cholesterol intake on serum lipids among Tehranian adults. In 443 subjects >or=18 y, dietary intake was assessed. Height and weight were measured and body mass index was calculated. Serum cholesterol, triacylglycerol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol levels were calculated. Cholesterol intakes >or=300 mg/d and saturated fat intakes >or=7% of total energy were defined as high intakes. Individuals were categorized into four groups based on cholesterol and saturated fat intakes. Subjects' mean age was 40.1 +/- 14.6 y; those in whom cholesterol and saturated fat intake was normal had significantly less energy and fat intake than those with high cholesterol and saturated fat intakes (P < 0.01). Saturated fat intake had a significant effect on serum total and HDL-C levels. Subjects with a normal saturated fat intake had significantly less serum total and HDL-C than those who had high saturated fat intake (P < 0.01 and P < 0.05, respectively). Adjusting for age, sex, and body mass index, the main effect of cholesterol intake on HDL-C was significant (P = 0.05). Mean serum HDL-C was lower in subjects who had normal cholesterol intake than in those with high cholesterol intake. These results show that cholesterol and saturated fat intakes have no combined effect on serum low-density lipoprotein cholesterol level, whereas cholesterol intake per se affects serum HDL-C level.
Tabara, Yasuharu; Ueshima, Hirotsugu; Takashima, Naoyuki; Hisamatsu, Takashi; Fujiyoshi, Akira; Zaid, Maryam; Sumi, Masaki; Kohara, Katsuhiko; Miki, Tetsuro; Miura, Katsuyuki
While alcohol consumption is known to increase plasma high-density lipoprotein (HDL) cholesterol levels, its relationship with low-density lipoprotein (LDL) cholesterol levels is unclear. Aldehyde dehydrogenase 2 (ALDH2) is a rate-controlling enzyme in alcohol metabolism, but a large number of Japanese people have the inactive allele. Here, we conducted a Mendelian randomization analysis using the ALDH2 genotype to clarify a causal role of alcohol on circulating cholesterol levels and lipoprotein particle numbers. This study was conducted in three independent general Japanese populations (men, n = 2289; women, n = 1940; mean age 63.3 ± 11.2 years). Alcohol consumption was assessed using a questionnaire. Lipoprotein particle numbers were determined by nuclear magnetic resonance spectroscopy. Alcohol consumption increased linearly in proportion to the number of subjects carrying the enzymatically active *1 allele in men (p < 0.001). The *1 allele was also positively associated with HDL cholesterol level (adjusted mean ± standard error, *1*1: 60 ± 0.5, *1*2: 56 ± 0.6, *2*2: 55 ± 1.3 mg/dl, p < 0.001) and inversely associated with LDL cholesterol level (116 ± 0.9, 124 ± 1.1, 130 ± 2.6 mg/dl, p < 0.001). The *1 allele was also positively associated with HDL particle numbers (per-allele: 2.60 ± 0.32 μmol/l, p < 0.001) and inversely associated with LDL particle numbers (-67.8 ± 19.6 nmol/l, p = 0.001). Additional Mendelian randomization analysis failed to clarify the involvement of cholesteryl ester transfer protein in alcohol-related changes in lipoprotein cholesterol levels. No significant association was observed in women, presumably due to their small amount of alcohol intake. Alcohol consumption has a causal role in not only increasing HDL cholesterol levels but also decreasing LDL cholesterol levels and particle numbers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Schreurs, Bernard G.; Sparks, D. Larry
Background Cholesterol-fed rabbits have been documented to show increased amyloid-β (Aβ) deposits in the brain that can be exacerbated by the quality of drinking water especially if rabbits drink tap water or distilled water containing copper. One mechanism of cholesterol and Aβ clearance may be through the ATP-binding cassette transporter A1 (ABCA1). Objective and Methods Using an ABCA1 antibody, we determined the number of ABCA1-immunopositive neurons in three areas of rabbit brain as a function of feeding 2% cholesterol and providing tap water, distilled water, or distilled water to which aluminum, copper, or zinc was added. Results The number of neurons with ABCA1 immunoreactivity was increased significantly as a result of dietary cholesterol in the rabbit hippocampus and inferior and superior temporal cortex. The number of neurons with ABCA1 immunoreactivity was further increased in all three areas as a result of cholesterol-fed rabbits drinking tap water or distilled water with copper. Finally, cholesterol-fed rabbits that drank distilled water with aluminum also showed an increased number of ABCA1-immunopositive neurons in inferior and superior temporal cortex. Conclusions These data suggest that ABCA1 levels increase in parallel with previously documented increases in Aβ levels as a result of high dietary cholesterol and copper in the drinking water. Addition of aluminum to distilled water may have a similar effect in the temporal cortex. ABCA1 has been proposed as a means of clearing Aβ from the brain and manipulations that increase Aβ also result in an increase of clearance machinery. PMID:26444796
Schreurs, Bernard G; Sparks, D Larry
Cholesterol-fed rabbits have been documented to show increased amyloid-β (Aβ) deposits in the brain that can be exacerbated by the quality of drinking water especially if rabbits drink tap water or distilled water containing copper. One mechanism of cholesterol and Aβ clearance may be through the ATP-binding cassette transporter A1 (ABCA1). Using an ABCA1 antibody, we determined the number of ABCA1-immunopositive neurons in three areas of rabbit brain as a function of feeding 2% cholesterol and providing tap water, distilled water, or distilled water to which aluminum, copper, or zinc was added. The number of neurons with ABCA1 immunoreactivity was increased significantly as a result of dietary cholesterol in the rabbit hippocampus and inferior and superior temporal cortex. The number of neurons with ABCA1 immunoreactivity was further increased in all three areas as a result of cholesterol-fed rabbits drinking tap water or distilled water with copper. Finally, cholesterol-fed rabbits that drank distilled water with aluminum also showed an increased number of ABCA1-immunopositive neurons in inferior and superior temporal cortex. These data suggest that ABCA1 levels increase in parallel with previously documented increases in Aβ levels as a result of high dietary cholesterol and copper in the drinking water. Addition of aluminum to distilled water may have a similar effect in the temporal cortex. ABCA1 has been proposed as a means of clearing Aβ from the brain and manipulations that increase Aβ also result in an increase of clearance machinery.
Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.
A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development.
van Zwieten, Rob; Bochem, Andrea E; Hilarius, Petra M; van Bruggen, Robin; Bergkamp, Ferry; Hovingh, G Kees; Verhoeven, Arthur J
Maintenance of the asymmetric distribution of phospholipids across the plasma membrane is a prerequisite for the survival of erythrocytes. Various stimuli have been shown to induce scrambling of phospholipids and thereby exposure of phosphatidylserine (PS). In two types of patients, both with aberrant plasma cholesterol levels, we observed an aberrant PS exposure in erythrocytes upon stimulation. We investigated the effect of high and low levels of cholesterol on the ATP-dependent flippase, which maintains phospholipid asymmetry, and the ATP-independent scrambling activity, which breaks down phospholipid asymmetry. We analyzed erythrocytes of a patient with spur cell anemia, characterized by elevated plasma cholesterol, and the erythrocytes of Tangier disease patients with very low levels of plasma cholesterol. In normal erythrocytes, loaded with cholesterol or depleted of cholesterol in vitro, the same analyses were performed. Changes in the cholesterol/phospholipid ratio of erythrocytes had marked effects on PS exposure upon cell activation. Excess cholesterol profoundly inhibited PS exposure, whereas cholesterol depletion led to increased PS exposure. The activity of the ATP-dependent flippase was not changed, suggesting a major influence of cholesterol on the outward translocation of PS. The effects of cholesterol were not accompanied by eminent changes in cytoskeletal and membrane proteins. These findings emphasize the importance of cholesterol exchange between circulating plasma and the erythrocyte membrane as determinant for phosphatidylserine exposure in erythrocytes.
Chaen, Hideto; Kinchiku, Shigesumi; Kajiya, Shoko; Uenomachi, Hitoshi; Yuasa, Toshinori; Takasaki, Kunitsugu; Ohishi, Mitsuru
Aim: Low-density lipoprotein cholesterol (LDL-C) is routinely estimated using the Friedewald equation [LDL-C(F)]. A novel method for LDL-C [LDL-C(M)] estimation recently proposed by Martin et al. was reported to be more accurate than the Friedewald formula in subjects in the United States. The validity of LDL-C(M) in different races and patients with diabetes mellitus (DM) has not been elucidated. The purpose of this study was to validate the LDL-C(M) estimates in Japanese population with type 2 DM by comparing with LDL-C(F) and directly measured LDL-C [LDL-C(D)]. Methods: Both LDL-C(M) and LDL-C(F) levels were compared against LDL-C(D) measured by selective solubilization method in 1,828 Japanese patients with type 2 DM. Results: On linear regression analysis, LDL-C(M) showed a stronger correlation than that shown by LDL-C(F) (R = 0.979 vs. R = 0.953, respectively) with LDL-C(D). We further analyzed the effect of serum triglyceride (TG) concentrations on the accuracy of LDL-C(F) and LDL-C(M). Although LDL-C levels showed a positive correlation with TG levels, the LDL-C(F) levels tended to show a greater divergence from LDL-C(D) levels than that shown by LDL-C(M) with changes in TG levels. Conclusion: We for the first time demonstrated a more useful measurement of LDL-C levels estimated by Martin's method than that estimated by the Friedewald equation in Japanese patients with DM. PMID:27592628
Cherubini, Antonella; Palomba, Andrea; Morosin, Marco; Russo, Giulia; Mazzone, Carmine; Barbati, Giulia; Tarantini, Luigi; Cioffi, Giovanni; Cattin, Luigi; Sinagra, Gianfranco; Di Lenarda, Andrea
It is known that less than half of patients with coronary heart disease reaches the target of LDL cholesterol (LDL-C) <100 mg/dl. According to the latest international guidelines, this target has been lowered to <70 mg/dl in very high-risk patients. From November 1, 2009 to December 31, 2012, 4953 patients with coronary heart disease were enrolled in the Cardiovascular Registry of Trieste (Italy). We assessed clinical data, LDL-C levels, statin prescription and medium-term outcome in patients with coronary heart disease. At first clinical evaluation, LDL-C values were available for only 61.5% of patients. The target level of LDL-C <70 mg/dl was reached in 17% of cases and LDL-C <100 mg/dl in 53%. Patients with lower LDL-C levels were more frequently males, with higher cardiovascular risk profile, more comorbidity and more frequent polypharmacy. LDL-C levels influenced statin prescription: in patients with LDL-C ≥ 100 mg/dl, cardiologists started or modified the dosage of statin therapy twice more than in patients with LDL-C <100 mg/dl, even if only in less than 20% of cases. Patients with LDL-C <100 mg/dl in statin therapy had better prognosis, whereas patients with low LDL-C levels without statin therapy had the worst prognosis. Other prognostic factors in this population with LDL-C <100 mg/dl were age, presence of heart failure, comorbidities (evaluated with Charlson index) and polypharmacy. In our population of outpatients with coronary heart disease, the target of LDL-C <100 mg/dl was reached in 53% of cases. LDL-C levels influenced statin prescription and modification of dosages. The medium-term outcome is closely influenced by the achievement of target LDL-C levels and statin prescription.
Tsun, Joseph G. S.; Yung, Susan; Chau, Mel K. M.; Shiu, Sammy W. M.; Chan, Tak Mao; Tan, Kathryn C. B.
Background Lipid accumulation has been shown to accelerate renal injury, and the intracellular accumulation of lipids may be caused by alterations in synthesis as well as lipid uptake and efflux. We have investigated the role of cellular cholesterol transport proteins including adenosine triphosphate binding cassette transporter A1 (ABCA1), G1 (ABCG1) and scavenger receptor class B type I (SR-BI) in diabetic nephropathy. Methods Protein expression and the ability to mediate cholesterol efflux of ABCA1, ABCG1 and SR-BI was determined in human renal mesangial cells and proximal tubular epithelial cells cultured under normal or high glucose conditions. Renal expression of these cholesterol transporters was examined in a murine model of streptozotocin-induced type 1 diabetes. Results ABCA1, ABCG1 and SR-BI were expressed in both human renal mesangial cells and proximal tubular epithelial cells, and mediated cholesterol efflux to apolipoprotein AI and HDL. In vitro, hyperglycemia reduced the expression and the ability to mediate cholesterol efflux of all three cholesterol transporters (p<0.05). In vivo studies showed that intra-renal accumulation of lipids was increased in diabetic mice, particularly in mice with nephropathy. This was associated with a significant reduction in the expression of ABCA1, ABCG1 and SR-BI in the kidneys. These changes were already seen in diabetic mice without nephropathy and preceded the development of nephropathy. Diabetic mice with nephropathy had the lowest level of these cholesterol transporters. Conclusion Inducing diabetes with streptozotocin significantly reduced renal expression of ABCA1, ABCG1 and SR-BI. Defects in cholesterol export pathway in renal cells could therefore promote cholesterol accumulation and might contribute to the development of diabetic nephropathy. PMID:25181357
Dwyer, J H; Rieger-Ndakorerwa, G E; Semmer, N K; Fuchs, R; Lippert, P
The current study was conducted to determine if smokers and nonsmokers differ in serum concentrations of high-density lipoprotein cholesterol (HDL-C) before smoking initiation and if a decline in HDL-C levels could be detected among adolescents during the first two years of smoking. Changes in HDL-C levels and smoking were observed longitudinally in 1983, 1984, and 1985 among 691 seventh and eighth graders (age range, 12 to 14 years) from two German cities; 82% were nonsmokers at baseline. For these baseline nonsmokers, no differences in baseline HDL-C concentrations were found between those who became smokers and those who remained nonsmokers. In contrast, those who became light (one to 39 cigarettes per week) or moderate (greater than or equal to 40 cigarettes per week) smokers by one or two years after the initial examination evidenced lower mean HDL-C concentrations relative to persistent nonsmokers at follow-up, constituting a decrement of -0.016 mmol/L [SE = .035] (-0.6 mg/dL) [SE = 1.4] for light smokers and -0.114 mmol/L [SE = .064] (-4.4 mg/dL) [SE = 2.5] for moderate smokers. These findings suggest that short-term exposure to cigarette smoke at low levels may have atherogenic consequences.
Di Paola, R; Marucci, A; Trischitta, V
A wide range of studies both in humans and animal models point GALNT2 as a shaper of serum HDL-C and TG levels. Available data in humans indicate that, while under conditions of extreme GALNT2 loss-of-function HDL-C is the main target, a fine-tuning of GALNT2 changes is mostly associated with TG levels. Understanding whether different degrees of GALNT2 change do modulate different serum lipid fractions and, if so, addressing the mechanisms underlying such pleiotropic effects has the potential not only to improve our understanding of HDL-C and TG metabolism, but also to make GALNT2 becoming a target for treating atherogenic dyslipidemia and related clinical events. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Wei, Xue-Biao; Chen, Feng; Huang, Jie-Leng; He, Peng-Cheng; Wei, Yan-Xing; Tan, Ning; Chen, Ji-Yan; Yu, Dan-Qing; Liu, Yuan-Hui
The monocyte to high-density lipoprotein cholesterol ratio (MHR) appears to be a newly emerging inflammatory marker. However, its prognostic value in patients with infective endocarditis (IE) and normal left ventricular ejection fraction (LVEF) has been unclear.Methods and Results:We enrolled consecutive patients with IE and normal LVEF and divided into 3 groups based on the tertiles of MHR. Of 698 included patients, 44 (6.3%) died while in hospital. The occurrence of in-hospital death (3.9%, 4.3%, and 10.8%, P=0.003) and of major adverse clinical events (MACEs) (15.6%, 20.9%, and 30.6%, P<0.001) increased from the lowest to the highest MHR tertiles, respectively. Receiver-operating characteristic analysis demonstrated that MHR had good predictive value for in-hospital death (area under the curve [AUC] 0.670, 95% confidence interval [CI] 0.58-0.76, P<0.001) and was similar to C-reactive protein (AUC 0.670 vs. 0.702, P=0.444). Furthermore, MHR >21.3 had a sensitivity of 74.4% and specificity of 57.6% for predicting in-hospital death. Multiple analysis showed that MHR >21.3 was an independent predictor of both in-hospital (odds ratio 3.98, 95% CI 1.91-8.30, P<0.001) and long-term death (hazard ratio 2.29, 95% CI 1.44-3.64, P<0.001) after adjusting for age, female, diabetes mellitus, estimated glomerular filtration rate <90 mL/min/1.73 m(2), and surgical treatment. Kaplan-Meier survival curves showed that patients with MHR >21.3 had an increased rate of long-term death compared to those without (P=0.002). Elevated MHR was independently associated with in-hospital and long-term death in patients with IE and normal LVEF.
Holme, Ingar; Tonstad, Serena
We aimed to clarify the strength of the association between conventional and metabolic risk factors to coronary heart disease (CHD) mortality across short, intermediate, and long periods of follow-up and whether the effects of risk factors are heterogeneous across serum cholesterol levels. The Oslo Study prospective cohort of 14,846 men aged 40-49 years was followed from screening in 1972-73 until 2006, during which time 1655 subjects died of CHD. Multivariate-adjusted Cox proportional models compared hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD mortality across 0-12, 12-24, and 24-33 years of follow-up. Interactions between risk factors and quartile level of total serum cholesterol were assessed. Total cholesterol, blood pressure, and cigarette smoking were associated with CHD mortality in multivariate analyses across all follow-up periods. Nonfasting triglyceride levels were associated with CHD in multivariate analyses (0-12 years, HR 1.12, 95% CI 1.00-1.25; 12-24 years, HR 1.13, 95% CI 1.04-1.23; 24-33 years, HR 1.09, 95% CI 1.00-1.19; 0-33 years, HR 1.10, 95% CI 1.05-1.16). A metabolic risk factor score (based on blood pressure, triglycerides, body mass index, and glucose) retained predictivity across all periods. The relations between systolic blood pressure, triglycerides, and metabolic risk factor score to CHD were stronger in the lower than the upper quartiles of serum cholesterol (p < 0.001). Conventional risk factors and nonfasting triglycerides increased CHD mortality across all periods of follow-up. The association with metabolic variables was strongest in men with low total cholesterol levels supporting the idea that lowering cholesterol should be the primary target of primary prevention.
Prasanthi, Jaya R.P.; Schrag, Matthew; Dasari, Bhanu; Marwarha, Gurdeep; Kirsch, Wolff M.; Ghribi, Othman
Accumulation of amyloid-β (Aβ) peptide and the hyperphosphorylation of tau protein are major hallmarks of Alzheimer’s disease (AD). The causes of AD are not well known but a number of environmental and dietary factors are suggested to increase the risk of developing AD. Additionally, altered metabolism of iron may have a role in the pathogenesis of AD. We have previously demonstrated that cholesterol-enriched diet causes AD-like pathology with iron deposition in rabbit brain. However, the extent to which chelation of iron protects against this pathology has not been determined. In this study, we administered the iron chelator deferiprone in drinking water to rabbits fed with a 2% cholesterol diet for 12 weeks. We found that deferiprone (both at 10 and 50 mg/kg/day) significantly decreased levels of Aβ40 and Aβ42 as well as BACE1, the enzyme that initiates cleavage of amyloid-β protein precursor to yield Aβ. Deferiprone also reduced the cholesterol diet-induced increase in phosphorylation of tau but failed to reduce reactive oxygen species generation. While deferiprone treatment was not associated with any change in brain iron levels, it was associated with a significant reduction in plasma iron and cholesterol levels. These results demonstrate that deferiprone confers important protection against hypercholesterolemia-induced AD pathology but the mechanism(s) may involve reduction in plasma iron and cholesterol levels rather than chelation of brain iron. We propose that adding an antioxidant therapy to deferiprone may be necessary to fully protect against cholesterol-enriched diet-induced AD-like pathology. PMID:22406440
Alkhouri, Naim; Eng, Katharien; Lopez, Rocio; Nobili, Valerio
Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular disease (CVD) risk in children. Non-high density lipoprotein-cholesterol (non-HDL-C) has been shown to be a good predictor of cardiovascular events. Recent data in adults found non-alcoholic steatohepatitis (NASH) to be associated with significantly higher levels of non-HDL-C than simple steatosis, suggestive it might be used as a non-invasive tool to diagnose NASH. The goal of our study was to assess non-HDL-C levels in children with NAFLD. Our cohort consisted of pediatric patients with biopsy-proven NAFLD. Anthropometric, laboratory, and histologic data were obtained on all patients. Univariable analysis was performed to assess differences in clinical characteristics between groups. Spearman rank correlation coefficients were calculated to assess the correlation between non-HDL-C levels and clinical variables. ANCOVA was used to adjust for possible confounders. 302 subjects with NAFLD were included in our study; 203 with NASH and 99 without NASH. Subjects with NASH had significantly higher non-HDL-C levels than those without (p = 0.004). Histologic features of NASH, including ballooning, inflammation, and fibrosis were found to be weakly correlated with non-HDL-C levels, (p < 0.05 for all). After adjusting for the presence of metabolic syndrome (MetS), ALT, and GGT, the association between non-HDL-C and NASH was not significant (p = 0.66). In Conclusion, non-HDL-C levels are higher in children with NASH than those with simple steatosis, suggesting increased CVD risk. This may be a reflection of the higher prevalence of MetS. Non-HDL-C had a positive association with histologic features of NASH.
Tsai, Ching-Wei; North, Kari E; Tin, Adrienne; Haack, Karin; Franceschini, Nora; Saroja Voruganti, V; Laston, Sandy; Zhang, Ying; Best, Lyle G; MacCluer, Jean W; Beaty, Terri H; Navas-Acien, Ana; Kao, W H Linda; Howard, Barbara V
Elevated LDL cholesterol (LDL-C) is an important risk factor for atherosclerosis and cardiovascular disease. Variants in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have been associated not only with plasma LDL-C concentration, but also with ischemic heart disease. Little is known about the genetic architecture of PCSK9 and its influence on LDL-C in American Indians. We aimed to investigate the genetic architecture in the 1p32 region encompassing PCSK9 and its influence on LDL-C in American Indians. The Strong Heart Family Study (SHFS) is a family-based genetic study. Two thousand four hundred fifty eight American Indians from Arizona, Oklahoma, North Dakota, and South Dakota, who were genotyped by Illumina MetaboChip. We genotyped 486 SNPs in a 3.9 Mb region at chromosome 1p32 encompassing PCSK9 in 2458 American Indians. We examined the association between these SNPs and LDL-C. For common variants (MAF ≥ 1%), meta-analysis across the three geographic regions showed common variants in PCSK9 were significantly associated with higher LDL-C. The most significant SNP rs12067569 (MAF = 1.7 %, β = 16.9 ± 3.7, P = 5.9 × 10(-6)) was in complete LD (r(2) = 1) with a nearby missense SNP, rs505151 (E670G) (β = 15.0 ± 3.6, P = 3.6 × 10(-5)). For rare variants (MAF < 1%), rs11591147 (R46L, MAF = 0.9%) was associated with lower LDL-C (β = - 31.1 ± 7.1, P = 1.4 × 10(-5)). The mean (SD) of LDL-C was 76.9 (7.8) and 107.4 (1.0) mg/dL for those with and without the R46L mutation, respectively. One person who was homozygous for R46L had LDL-C levels of 11 mg/dL. In one family, 6 out of 8 members carrying the R46L mutation had LDL-C levels below the lower 10% percentile of LDL-C among all study participants. Both rare and common variants in PCSK9 influence plasma LDL-C levels in American Indians. Follow-up studies may disclose the influence of these mutations on the risk of CVD and responses to cholesterol-lowering medications.
North, Kari E.; Tin, Adrienne; Haack, Karin; Franceschini, Nora; Saroja Voruganti, V.; Laston, Sandy; Zhang, Ying; Best, Lyle G.; MacCluer, Jean W.; Beaty, Terri H.; Kao, W. H. Linda; Howard, Barbara V.
Context: Elevated LDL cholesterol (LDL-C) is an important risk factor for atherosclerosis and cardiovascular disease. Variants in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have been associated not only with plasma LDL-C concentration, but also with ischemic heart disease. Little is known about the genetic architecture of PCSK9 and its influence on LDL-C in American Indians. Objective: We aimed to investigate the genetic architecture in the 1p32 region encompassing PCSK9 and its influence on LDL-C in American Indians. Design: The Strong Heart Family Study (SHFS) is a family-based genetic study. Participants: Two thousand four hundred fifty eight American Indians from Arizona, Oklahoma, North Dakota, and South Dakota, who were genotyped by Illumina MetaboChip. Results: We genotyped 486 SNPs in a 3.9 Mb region at chromosome 1p32 encompassing PCSK9 in 2458 American Indians. We examined the association between these SNPs and LDL-C. For common variants (MAF ≥ 1%), meta-analysis across the three geographic regions showed common variants in PCSK9 were significantly associated with higher LDL-C. The most significant SNP rs12067569 (MAF = 1.7 %, β = 16.9 ± 3.7, P = 5.9 × 10−6) was in complete LD (r2 = 1) with a nearby missense SNP, rs505151 (E670G) (β = 15.0 ± 3.6, P = 3.6 × 10−5). For rare variants (MAF < 1%), rs11591147 (R46L, MAF = 0.9%) was associated with lower LDL-C (β = − 31.1 ± 7.1, P = 1.4 × 10−5). The mean (SD) of LDL-C was 76.9 (7.8) and 107.4 (1.0) mg/dL for those with and without the R46L mutation, respectively. One person who was homozygous for R46L had LDL-C levels of 11 mg/dL. In one family, 6 out of 8 members carrying the R46L mutation had LDL-C levels below the lower 10% percentile of LDL-C among all study participants. Conclusions: Both rare and common variants in PCSK9 influence plasma LDL-C levels in American Indians. Follow-up studies may disclose the influence of these mutations on the risk of CVD and responses
Arold, Stephen; Sullivan, Patrick; Bilousova, Tina; Teng, Edmond; Miller, Carol A.; Poon, Wayne W.; Vinters, Harry V.; Cornwell, Lindsey B.; Saing, Tommy; Cole, Gregory M.
The apolipoprotein E4 allele (APOE4) contributes to Alzheimer’s disease (AD) risk and APOE2 is protective, but the relevant cellular mechanisms are unknown. We have used flow cytometry analysis to measure apolipoprotein E (apoE) and amyloid beta peptide (Aβ) levels in large populations of synaptic terminals from AD and aged cognitively normal controls, and demonstrate that modest but significant increases in soluble apoE levels accompany elevated Aβ in AD cortical synapses and in an APP/PS1 rat model of AD. Dual labeling experiments document co-localization of apoE and Aβ in individual synapses with concentration of Aβ in a small population of apoE-positive synapses in both AD and controls. Consistent with a clearance role, the apoE level was higher in Aβ-positive synapses in control cases. In aged targeted replacement mice expressing human apoE, apoE2/4 synaptic terminals demonstrated the highest level of apoE and the lowest level of Aβ compared to apoE3/3 and apoE4/4 lines. In apoE2/4 terminals, the pattern of immunolabeling for apoE and Aβ closely resembled the pattern in human control cases, and elevated apoE was accompanied by elevated free cholesterol in apoE2/4 synaptic terminals. These results are consistent with a role for APOE in Aβ clearance in AD synapses, and suggest that optimal lipidation of apoE2 compared to E3 and E4 makes an important contribution to Aβ clearance and synaptic function. PMID:22020632
Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark
Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.
Winitz, M. (Inventor)
By feeding a human subject as the sole source of sustenance a defined diet wherein the carbohydrate consists substantially entirely of glucose, maltose or a polysaccharide of glucose, the blood serum cholesterol level of the human subject is substantially reduced. If 25 percent of the carbohydrate is subsequently supplied in the form of sucrose, an immediate increase from the reduced level is observed. The remainder of the defined diet normally includes a source of amino acids, such as protein or a protein hydrolysate, vitamins, minerals and a source of essential fatty acid.
Fears, R; Richards, D H; Ferres, H
Compactin, [7-(1,2,6,7,8,8a-hexahydro-2-methyl-8-(2-methylbutyrylox)naphthyl)-3-hydroxyheptan-5-olide], a potent competitive inhibitor of the rate-determining step in cholesterol biosynthesis, was used to study the influence of changes in cholesterogenesis on serum cholesterol levels. Up to 3 h after a single oral dose (20 or 50 mg/kg) or after the last of a series of daily oral doses (50 mg/kg for 7 or 28 days) to young, male normolipidaemic rats, compactin consistently inhibited cholesterogenesis measured using 3H20 in liver, ileum and other extrahepatic tissues without affecting fatty acid synthesis. Compactin did not reduce serum or tissue cholesterol nor affect the serum concentration of other lipids nor the ratio between lipoprotein classes. A diurnal variation in the effect of compactin on cholesterogenesis was observed. For example, by 12--20 h after dosing, cholesterogenesis at all sites was increased above the comparable control value, indicating the induction of enzyme synthesis and overall there was little effect on the mass of cholesterol synthesized per day. Similar results were obtained using male chicks. Inhibition of cholesterogenesis by compactin was also observed in cholestyramine-treated rats, in which cholesterol turnover was markedly increased, and even in cholesterol-fed rats, in which cholesterogenesis already was repressed. In neither case, however, was inhibition of cholesterogenesis accompanied by a hypocholesterolaemic effect. It is concluded that a more persistent suppression of cholesterogenesis, than that observed with compactin in the rat, may be required in order to affect serum cholesterol concentrations.
Pan, Si-Yuan; Dong, Hang; Guo, Bao-Feng; Zhang, Yi; Yu, Zhi-Ling; Fong, Wang-Fun; Han, Yi-Fan; Ko, Kam-Ming
Schisandrin B, an active ingredient isolated from the fruit of Schisandra chinensis, increased serum and hepatic triglyceride levels in mice. In the present study, the effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice without and with the influence of fenofibrate were investigated. Parameters on hepatic index (the ratio of liver weight to body weight × 100) were also analyzed. Mice were intragastrically treated with schisandrin B at a single dose of 0.2, 0.4, 0.8, or 1.6 g/kg, without or with fenofibrate pretreatment (0.1 g/kg/day for 4 days, p.o.). Twenty-four hours after schisandrin B treatment, serum/hepatic triglyceride and total cholesterol levels were measured. Schisandrin B treatment dose-dependently increased serum and hepatic triglyceride levels as well as hepatic index in mice. In contrast, hepatic total cholesterol levels were decreased in a dose-dependent manner in schisandrin B-treated mice. Data obtained from effective kinetics analysis indicated that the action of schisandrin B on serum triglyceride had a higher specificity than those on hepatic total cholesterol and hepatic index. While fenofibrate pretreatment inhibited the schisandrin B-induced elevation in serum triglyceride levels, it completely abrogated the elevation of hepatic triglyceride levels in schisandrin B-treated mice. The combined treatment with schisandrin B and fenofibrate decreased hepatic total cholesterol level and increased the hepatic index in an additive or semi-additive manner, respectively. In conclusion, the results of effective kinetics analysis indicated that the schisandrin B-induced hypertriglyceridemia was competitively inhibited by fenofibrate. Schisandrin B may offer the prospect of setting up a mouse model of hypertriglyceridemia and fatty liver for screening triglyceride-lowering drug candidates.
Scharinger, Bernhard; Messner, Barbara; Türkcan, Adrian; Schuster, Daniela; Vuorinen, Anna; Pitterl, Florian; Heinz, Katharina; Arnhard, Kathrin; Laufer, Günther; Grimm, Michael; Stuppner, Hermann; Oberacher, Herbert; Eller, Philipp; Ritsch, Andreas; Bernhard, David
The health benefit through the control of lipid levels in hyperlipidaemic individuals is evident from a large number of studies. The pharmacological options to achieve this goal shall be as specific and personalized as the reasons for and co-factors of hyperlipidaemia. It was the goal of this study to reveal the impact of leoligin on cholesterol levels and to define its mechanism of action. Oral application of leoligin in ApoE-/- mice led to significantly reduced total serum cholesterol levels and a reduction in postprandial blood glucose peak levels. In the absence of biochemical signs of toxicity, leoligin treatment resulted in reduced weight gain in mice. The effects of leoligin on serum cholesterol levels may be due to a direct inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) by a unique, non-statin-like binding mode. Postprandial serum glucose peaks may be reduced by a mild peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonistic activity of leoligin. No effect on atherosclerotic plaque size was observed. As a non-toxic, cholesterol-, peak glucose-, and weight gain-lowering compound, leoligin continues to fulfil characteristics of a potential agent for the treatment of cardiovascular disease (CVD). The counterregulatory overexpression of hepatic HMGCR in leoligin treated animals possibly explains the missing permanent anti-atherosclerotic effect.
Broitman, S A
Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.
Ding, Rong-jing; Ma, Chang-sheng; Chen, Hong; Wu, Yan; Yang, Xin-chun; Hua, Qi; Li, Rui-jie; Ren, Wen-lin; Wang, Ming-sheng; Xiang, Xiao-ping; Du, Xin; Pi, Lin; Hu, Da-yi
To investigate the low-density lipoprotein cholesterol (LDL-C) levels in outpatients with coronary heart disease (CHD) visiting cardiology outpatient clinics of 8 hospitals in Beijing. A total of 903 outpatients with CHD were enrolled from 4 three-tier hospitals and 4 two-tier hospitals in Beijing. All patients were asked to finish the questionnaire including demographic data, CHD history, the knowledge on cholesterol, and the use of statins. Blood lipid was examined and the LDL-C control rate and related factors were then analyzed. Questionnaire was obtained from 876 patients [619 male: 70.7%, mean age: (64.9 ± 10.7) years old] and blood lipid data were available in 709 patients. The general LDL-C control rate was 36.9% (262/709) and was 13.5% (27/173) in very high risk CHD patients, and lower in patients treated in two-tier hospitals than patients treated in three-tier hospitals[31.3% (121/386) vs. 43.7% (141/323), P < 0.01], in female patients than in male patients [27.1% (60/261) vs. 41.3% (201/496), P < 0.01] and in diabetic patients than in non-diabetic patients [13.5% (27/200) vs. 44.7% (197/441), P < 0.01]. The LDL-C control rate was lower in patients less than 60 years old and patients over 80 years old than that in 60-70 years old patients and 70 - 80 years old patients (P < 0.05). LDL-C control rate was not affected by the history of hypertension, percutaneous coronary intervention or coronary artery bypass grafting, smoking, lipid examination frequency, knowledge on goal level of LDL-C, diet control and regularly physical exercising (all P > 0.05). There were 18.2% (129/709) patients not taking statins or not aware if they were taking statin or not. The main reason for not taking statin [47.9% (23/48)] was statin was no prescribed by doctors, followed by withdrawal by patients due to various reasons [27.1% (13/48)]. LDL-C control rate was low in patients with CHD visiting cardiology outpatient clinics in Beijing. The CHD patients and cardiologists
Das, S S; Chaudhary, R; Khetan, D; Shukla, J S; Agarwal, P; Mishra, R B
It is well known that citrate induces ionized hypocalcaemia by the chelating effect during plateletpheresis. However, the kinetics of serum magnesium (Mg) ions has not been well documented. We, therefore, evaluated biochemical changes in healthy donors during plateletpheresis procedure. Ten healthy donors underwent plateletpheresis on continuous cell separator (CS3000, Baxter, Round Lake, IL, USA) and 10 on intermittent flow cell separator (MCS 3p, Hemonetics, Braintree, MA, USA). Serum levels of total and ionized calcium (tCa and iCa, respectively) and Mg (tMg and iMg, respectively) were measured before, during and after the procedures. Although, the fall in tCa (from 2.62 +/- 0.12 to 2.36 +/- 0.12 mmol L(-1)) and tMg (from 0.89 +/- 0.01 to 0.79 +/- 0.01 mmol L(-1)) was modest and not significant; drop in iCa (from 1.33 +/- 0.1 to 0.84 +/- 0.1 mmol L(-1)) and iMg (from 0.53 +/- 0.01 to 0.35 +/- 0.1 mmol L(-1)) was statistically significant (P < 0.001). There were no significant differences observed between the CS3000 and MCS 3p cell separators regarding the fall in Ca and Mg. None of the donors experienced any adverse reactions during the procedures. In the study, an acute ionized hypocalcaemia and hypomagnesaemia have been observed after the plateletpheresis; therefore, measurement of both the ions may be monitored. However, there is no justification for prophylactic supplementation of either of these elements.
Romanenko, Victor G; Rothblat, George H; Levitan, Irena
Membrane potential of aortic endothelial cells under resting conditions is dominated by inward-rectifier K(+) channels belonging to the Kir 2 family. Regulation of endothelial Kir by membrane cholesterol was studied in bovine aortic endothelial cells by altering the sterol composition of the cell membrane. Our results show that enriching the cells with cholesterol decreases the Kir current density, whereas depleting the cells of cholesterol increases the density of the current. The dependence of the Kir current density on the level of cellular cholesterol fits a sigmoid curve with the highest sensitivity of the Kir current at normal physiological levels of cholesterol. To investigate the mechanism of Kir regulation by cholesterol, endogenous cholesterol was substituted by its optical isomer, epicholesterol. Substitution of approximately 50% of cholesterol by epicholesterol results in an early and significant increase in the Kir current density. Furthermore, substitution of cholesterol by epicholesterol has a stronger facilitative effect on the current than cholesterol depletion. Neither single channel properties nor membrane capacitance were significantly affected by the changes in the membrane sterol composition. These results suggest that 1) cholesterol modulates cellular K(+) conductance by changing the number of the active channels and 2) that specific cholesterol-protein interactions are critical for the regulation of endothelial Kir. PMID:12496090
... Venous Thromboembolism Aortic Aneurysm More Good vs. Bad Cholesterol Updated:Apr 3,2017 Cholesterol can't dissolve ... test . View an animation of cholesterol . LDL (Bad) Cholesterol LDL cholesterol is considered the “bad” cholesterol because ...
Limon, Onder; Sahin, Erkan; Kantar, Funda Ugur; Oray, Deniz; Ugurhan, Asli Aydinoglu
Acute pancreatitis can have a variable presentation and diagnosis is based on clinical presentation, serum amylase and lipase levels and computed tomography. Negative predictive value of serum lipase in diagnosing acute pancreatitis is approximately to 100 percent and a normal blood lipase level in acute pancreatitis is an extremely rare condition. Here we reported two cases with normal serum amylase and lipase levels.
To date, most of the major types of Kir channels, Kir2s, Kir3s, Kir4s and Kir6s, have been found to partition into cholesterol-rich membrane domains and/or to be regulated by changes in the level of membrane cholesterol. Surprisingly, however, in spite of the structural similarities between different Kirs, effects of cholesterol on different types of Kir channels vary from cholesterol-induced decrease in the current density (Kir2 channels) to the loss of channel activity by cholesterol depletion (Kir4 channels) and loss of channel coupling by different mediators (Kir3 and Kir6 channels). Recently, we have gained initial insights into the mechanisms responsible for cholesterol-induced suppression Kir2 channels, but mechanisms underlying cholesterol sensitivity of other Kir channels are mostly unknown. The goal of this review is to present a summary of the current knowledge of the distinct effects of cholesterol on different types of Kir channels in vitro and in vivo. PMID:19548316
Freeman, Michael R; Solomon, Keith R
Cholesterol is a neutral lipid that accumulates in liquid-ordered, detergent-resistant membrane domains called lipid rafts. Lipid rafts serve as membrane platforms for signal transduction mechanisms that mediate cell growth, survival, and a variety of other processes relevant to cancer. A number of studies, going back many years, demonstrate that cholesterol accumulates in solid tumors and that cholesterol homeostasis breaks down in the prostate with aging and with the transition to the malignant state. This review summarizes the established links between cholesterol and prostate cancer (PCa), with a focus on how accumulation of cholesterol within the lipid raft component of the plasma membrane may stimulate signaling pathways that promote progression to hormone refractory disease. We propose that increases in cholesterol in prostate tumor cell membranes, resulting from increases in circulating levels or from dysregulation of endogenous synthesis, results in the coalescence of raft domains. This would have the effect of sequestering positive regulators of oncogenic signaling within rafts, while maintaining negative regulators in the liquid-disordered membrane fraction. This approach toward examining the function of lipid rafts in prostate cancer cells may provide insight into the role of circulating cholesterol in malignant growth and on the potential relationship between diet and aggressive disease. Large-scale characterization of proteins that localize to cholesterol-rich domains may help unveil signaling networks and pathways that will lead to identification of new biomarkers for disease progression and potentially to novel targets for therapeutic intervention.
Arnqvist, Lisa; Dutta, Paresh C.; Jonsson, Lisbeth; Sitbon, Folke
Transgenic potato (Solanum tuberosum cv Désirée) plants overexpressing a soybean (Glycine max) type 1 sterol methyltransferase (GmSMT1) cDNA were generated and used to study sterol biosynthesis in relation to the production of toxic glycoalkaloids. Transgenic plants displayed an increased total sterol level in both leaves and tubers, mainly due to increased levels of the 24-ethyl sterols isofucosterol and sitosterol. The higher total sterol level was due to increases in both free and esterified sterols. However, the level of free cholesterol, a nonalkylated sterol, was decreased. Associated with this was a decreased glycoalkaloid level in leaves and tubers, down to 41% and 63% of wild-type levels, respectively. The results show that glycoalkaloid biosynthesis can be down-regulated in transgenic potato plants by reducing the content of free nonalkylated sterols, and they support the view of cholesterol as a precursor in glycoalkaloid biosynthesis. PMID:12692338
Porter, Forbes D.; Herman, Gail E.
Cholesterol homeostasis is critical for normal growth and development. In addition to being a major membrane lipid, cholesterol has multiple biological functions. These roles include being a precursor molecule for the synthesis of steroid hormones, neuroactive steroids, oxysterols, and bile acids. Cholesterol is also essential for the proper maturation and signaling of hedgehog proteins, and thus cholesterol is critical for embryonic development. After birth, most tissues can obtain cholesterol from either endogenous synthesis or exogenous dietary sources, but prior to birth, the human fetal tissues are dependent on endogenous synthesis. Due to the blood-brain barrier, brain tissue cannot utilize dietary or peripherally produced cholesterol. Generally, inborn errors of cholesterol synthesis lead to both a deficiency of cholesterol and increased levels of potentially bioactive or toxic precursor sterols. Over the past couple of decades, a number of human malformation syndromes have been shown to be due to inborn errors of cholesterol synthesis. Herein, we will review clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, HEM dysplasia, X-linked dominant chondrodysplasia punctata, Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like deficiency, and Antley-Bixler syndrome. PMID:20929975
Bouguerra, S. Aouichat; Benazzoug, Y.; Bekkhoucha, F.; Bourdillon, M. C.
To simulate diabetic conditions, the effects of high glucose concentration on collagen synthesis and cholesterol level in cultured aortic smooth muscle cells of Psammomys were investigated. For collagen biosynthesis, smooth muscle cells (SMCs) were incubated in synthetic proliferative phase and in postconfluent phase with 3H-proline. Cellular cholesterol was determined by enzymatic method. Under high glucose concentration, the results showed morphological modifications characterized by morphometric cellular, nuclear, and nucleolar changes. In biochemical studies, the authors observed an increase of free and esterified cellular cholesterol as well as of total proteins, collagen biosynthesis, and α1 (I+III) and α2 (I) chains of collagen contained in the SMCs and in the extracellular matrix. These results showed the sensitivity of Psammomys aortic SMCs to high glucose concentration and would constitute an interesting cellular model to study atherosclerosis pathogeny in experimental diabetes. PMID:15512791
... ve ever gone to the grocery store or food market, you've probably seen foods with labels on them that say "low in ... body. You also can get cholesterol from the foods you eat. Meat, fish, eggs, butter, cheese, and whole or low-fat milk all have cholesterol in ...
Bongard, Vanina; Dallongeville, Jean; Arveiler, Dominique; Ruidavets, Jean-Bernard; Amouyel, Philippe; Wagner, Aline; Ferrières, Jean
Controlling low-density lipoprotein (LDL)-cholesterol concentration is of tremendous importance to reduce cardiovascular risk. To investigate the attainment of LDL-cholesterol targets recommended in French and European guidelines on cardiovascular prevention, according to levels of cardiovascular risk. Participants aged 35 to 74 years (n=4609) were randomly selected from the general population of three French regions. A standardized data collection was performed to assess cardiovascular risk as described in the French and European guidelines. Overall, 17.5% of participants were considered to be at high risk and 25.4% at high or very high risk, according to the French and European guidelines, respectively. Only 1.2% of participants with no cardiovascular risk factors according to the French guidelines had an LDL-cholesterol concentration above the recommended target, whereas 82.5% of high-risk subjects did not attain their goal (70.8% among high-risk subjects receiving lipid-lowering therapy). Among untreated people, the median reduction in LDL-cholesterol needed to reach target ranged from 6.6% (lowest-risk groups) to 36.0% (highest-risk subjects). When risk was classified according to the European guidelines, the majority of participants did not reach the recommended LDL-cholesterol targets, irrespective of their level of risk or lipid-lowering therapy. In a majority of primary prevention candidates with multiple risk factors and in most high-risk subjects, LDL-cholesterol targets recommended by French guidelines are not being achieved, either because of insufficient treatment or because subjects are not recognized as being at risk. More stringent targets proposed by the European guidelines are not being achieved in most cases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Background The consumption of foods containing probiotic and prebiotic ingredients is growing consistently every year, and in view of the limited number of studies investigating their effect in the elderly. Objective The objective of this study was to evaluate the effect of the consumption of a symbiotic shake containing Lactobacillus acidophilus, Bifidobacterium bifidum and fructooligosaccharides on glycemia and cholesterol levels in elderly people. Methods A randomized, double-blind, placebo-controlled study was conducted on twenty volunteers (ten for placebo group and ten for symbiotic group), aged 50 to 60 years. The criteria for inclusion in the study were: total cholesterol > 200 mg/dL; triglycerides > 200 mg/dL and glycemia > 110 mg/dL. Over a total test period of 30 days, 10 individuals (the symbiotic group) consumed a daily dose of 200 mL of a symbiotic shake containing 108 UFC/mL Lactobacillus acidophilus, 108 UFC/mL Bifidobacterium bifidum and 2 g oligofructose, while 10 other volunteers (the placebo group) drank daily the same amount of a shake that did not contain any symbiotic bacteria. Blood samples were collected 15 days prior to the start of the experiment and at 10-day intervals after the beginning of the shake intake. The standard lipid profile (total cholesterol, triglycerides and HDL cholesterol) and glycemia, or blood sugar levels, were evaluated by an enzyme colorimetric assay. Results The results of the symbiotic group showed a non-significant reduction (P > 0.05) in total cholesterol and triglycerides, a significant increase (P < 0.05) in HDL cholesterol and a significant reduction (P < 0.05) in fasting glycemia. No