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1

Unusual high-density lipoprotein subclass distribution during late pregnancy.  

PubMed

Plasma lipoprotein distribution during late pregnancy is unusual since high-density lipoprotein (HDL) levels are increased in the presence of hypertriglyceridemia; the latter is usually associated with decreases in HDL levels. To determine whether there is a relationship between late-pregnancy lipid levels and specific HDL subclasses, HDL size distribution was determined by nondenaturing gradient gel electrophoresis (GGE) in a group of 36 women at 35 to 36 weeks of gestation and again at 6 weeks' postpartum, and in a group of 10 nonpregnant women. At 35 to 36 weeks of gestation, plasma triglyceride (TG) and cholesterol concentrations were significantly increased over postpartum levels (218 +/- 62 v 112 +/- 69 mg/dL and 234 +/- 48 v 197 +/- 36 mg/dL, respectively). During late pregnancy, apolipoprotein A-I (apo A-I) and HDL cholesterol concentrations were also increased relative to postpartum levels (211 +/- 42 v 168 +/- 20 mg/dL and 63 +/- 13 v 53 +/- 11 mg/dL, respectively). GGE analysis indicated that at 35 to 36 weeks of gestation, 86% of the subjects had a substantial increase of the most buoyant and largest of the HDL species, HDL2b; postpartum and nonpregnant HDL subclass distribution was characterized by the predominance of HDL3a, which are smaller, more dense HDL. The shift in the HDL subclass distribution during late pregnancy was associated with significant positive correlations between HDL2b and apo A-I (r = .50, P < .05) and HDL cholesterol (r = .60, P < .001). There were significant elevations in the concentrations of cholesteryl ester transfer protein (CETP) and estrogen during late pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8246775

Silliman, K; Tall, A R; Kretchmer, N; Forte, T M

1993-12-01

2

Relationship between total cholesterol\\/high-density lipoprotein cholesterol ratio, triglyceride\\/high-density lipoprotein cholesterol ratio, and high-density lipoprotein subclasses  

Microsoft Academic Search

Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. This study evaluated the relationship between plasma total cholesterol (TC)\\/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)\\/HDL-C ratio, and HDL subclass distribution. The apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 442

Lianqun Jia; Shiyin Long; Mingde Fu; Bingyu Yan; Ying Tian; Yanhua Xu; Lantu Gou

2006-01-01

3

Low-density lipoprotein subclass patterns and lipoprotein response to a reduced-fat diet in men  

Microsoft Academic Search

Low-density lipoprotein (LDL) subclass pattern B is a common genetically influenced lipoprotein profile characterized by a predominance of small, dense LDL particles, and associated with increased levels of triglyceride-rich lipoproteins, reductions in high-density lipoprotein cholesterol (HDL-C), and increased risk of coronary artery disease compared to individuals with a predominance of larger LDL (pattern A). We sought to determine whether LDL

HARRIETT A. FERNSTROM; BONNIE MILLER; RONALD M. KRAVSS

4

The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution  

Microsoft Academic Search

OBJECTIVE: To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. METHODS: Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. RESULTS:

Li Tian; Yanhua Xu; Mingde Fu; Tao Peng; Yinghui Liu; Shiyin Long

2011-01-01

5

Relationship between apolipoprotein C-III concentrations and high-density lipoprotein subclass distribution  

Microsoft Academic Search

High-density lipoprotein (HDL) subclasses have different antiatherogenic potentials and functional properties. This work presents our findings and discussions on their metabolic implications on apolipoprotein (apo) C-III together with other apolipoprotein levels and HDL subclass distribution profile. Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis coupled with immunodetection in 511 subjects. Concentrations of triglycerides and of

Li Tian; Jin Wu; Mingde Fu; Yanhua Xu; Lianqun Jia

2009-01-01

6

Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women.  

PubMed

To understand the mechanism responsible for maternal hyperlipidemia, 25 healthy pregnant women were studied longitudinally during the three trimesters of gestation and at post-partum, and 11 were studied again at post-lactation. Triglyceride and cholesterol levels increased with gestation in all the lipoprotein fractions. However, the greatest change appeared in low density (LDL) and high density (HDL) lipoproteins, both of which showed an increase in their triglyceride/cholesterol ratio. The proportional distribution of HDL subfractions showed that the HDL2b fraction was the only one that increased with gestation, whereas both HDL3a and HDL3b had the greatest decrease. Cholesteryl ester transfer protein activity increased during the second trimester of gestation. While postheparin lipoprotein lipase activity decreased during the third trimester, postheparin hepatic lipase activity progressively decreased from the first trimester. The 17 beta-estradiol, progesterone, and prolactin hormones progressively increased from the first trimester of gestation. The lipoprotein-triglyceride values correlated linearly and negatively with the logarithm of either postheparin lipase activities, HDL-triglycerides showing the highest correlation coefficient when plotted against the hepatic lipase values (r = -0.757). It appeared that the highest correlation between any of the HDL subclasses and the activity of the enzymes was for hepatic lipase activity versus HDL2b (r = 0.456) or HDL3a (r = 0.519). A significant lineal correlation also appeared between the postheparin hepatic lipase activity and the logarithm of any of the sex hormones studied, the highest value corresponding to estradiol (r = -0.783). Therefore, during gestation, the effect of estrogen in enhancing very low density lipoprotein (VLDL) production and decreasing hepatic lipase activity plays a key role in the accumulation of triglycerides in lipoproteins of density higher than VLDL. PMID:9026528

Alvarez, J J; Montelongo, A; Iglesias, A; Lasunción, M A; Herrera, E

1996-02-01

7

Characteristics of High-density Lipoprotein Subclasses Distribution for Subjects with Desirable Total Cholesterol Levels  

Microsoft Academic Search

Background  To investigate alteration of high density lipoproteins (HDL) subclasses distribution in different total cholesterol (TC) levels,\\u000a mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection.\\u000a 486 Chinese Adults subjects were assigned to different TC groups according to the

Li Tian; Shiyin Long; Mingde Fu; Yinghui Liu; Yanhua Xu; Lianqun Jia

2011-01-01

8

Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence  

Microsoft Academic Search

Several studies have reported an inverse relation- ship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations. The purpose of the present study was to determine whether genetic and pharmacological variation in hepatic lipase activity alters the distribution of HDL subclasses. Two independent ana- lytical methods (nuclear magnetic resonance and gradient gel electrophoresis) were used to compare

Scott M. Grundy; Gloria L. Vega; James D. Otvos; David L. Rainwater

9

Variations in High-Density Lipoprotein Subclasses During the Menstrual Cycle  

PubMed Central

In a study of 41 healthy premenopausal women, plasma high-density lipoprotein-2a (HDL2a) levels (ie, HDL of diameter 8.8 to 9.7 nm) were significantly higher during the luteal phase than during the follicular phase of the cycle. There was no significant variation in HDL2b or any of the HDL3 subclasses.

Williams, Paul T.; Austin, Melissa A.; Krauss, Ronald M.

2010-01-01

10

Variations in high-density lipoprotein subclasses during the menstrual cycle.  

PubMed

In a study of 41 healthy premenopausal women, plasma high-density lipoprotein-2a (HDL2a) levels (ie, HDL of diameter 8.8 to 9.7 nm) were significantly higher during the luteal phase than during the follicular phase of the cycle. There was no significant variation in HDL2b or any of the HDL3 subclasses. PMID:7968600

Williams, P T; Austin, M A; Krauss, R M

1994-11-01

11

Effects of dietary fat on high-density-lipoprotein subclasses are influenced by both apolipoprotein E isoforms and low-density-lipoprotein subclass patterns.  

PubMed

We examined the effects of replacing dietary fat with carbohydrates on high-density-lipoprotein (HDL) subclasses as measured by nondenaturing polyacrylamide-gradient-gel electrophoresis. One hundred five men received a 6-wk low-fat diet (24% of total energy) and a 6-wk high-fat diet (46% of energy) in a crossover design. Absorbency of protein stain was measured within five HDL subclasses: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). The low-density-lipoprotein-(LDL) subclass pattern was determined by gradient-gel electrophoresis, with pattern B men defined as having an LDL-predominant peak diameter < or = 25.5 nm and an LDL distribution skewed toward larger size particles. On the high-fat diet, 18 men exhibited LDL-subclass pattern B and 87 men exhibited the alternative LDL pattern A. Twelve men had the apolipoprotein (apo) epsilon 2 allele. Replacing dietary fat with carbohydrates 1) significantly decreased HDL3a, HDL2a, and HDL2b; 2) reduced HDL2b significantly more in pattern A than in pattern B men; and 3) increased plasma HDL3b concentrations significantly more in those men with the epsilon 2 allele. Our results suggest that unfavorable HDL changes were significantly more likely to occur in men who had LDL-subclass pattern A or the apo epsilon allele than in men who had pattern B or lacked the epsilon 2 allele. PMID:7762523

Williams, P T; Dreon, D M; Krauss, R M

1995-06-01

12

Characteristics of High-density Lipoprotein Subclasses Distribution for Subjects with Desirable Total Cholesterol Levels  

PubMed Central

Background To investigate alteration of high density lipoproteins (HDL) subclasses distribution in different total cholesterol (TC) levels, mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms. Methods ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection. 486 Chinese Adults subjects were assigned to different TC groups according to the third Report of NCEP (ATP- III) guidelines. Results The increase in contents of small pre?1-HDL, HDL3c, HDL3b, and HDL3a particles clustered and reduce in HDL2b with increased of TC. The distribution of HDL subclasses have shown abnormality characterized by the lower HDL2b (324.2 mg/L) contents and the higher pre?1-HDL (90.4 mg/L) contents for desirable TC Chinese subjects. Among 176 desirable TC subjects, 58.6% subjects with triglyceride (TG) < 2.26 mmol/L, 61.2% subjects with HDL-C ?1.03 mmol/L and 88.6% subjects with low density lipoprotein cholesterol(LDL-C) < 3.34 mmol/L, and the profile of HDL subclasses distribution for above these subjects was reasonable. Conclusions The particles size of HDL subclasses shifted towards smaller with increased TC levels. The TC was liner with HDL2b contents and those can be reduced 17 mg/L for 0.5 mmol/L increment in TC levels. The HDL subclasses distribution phenotype was not expectation for Chinese Population with desirable TC levels. Thus, from the HDL subclasses distribution point, when assessing the coronary heart disease(CHD) risk not only rely on the TC levels, but also the concentrations of TG, HDL-C and LDL-C must considered in case the potential risk for desirable TC subjects with other plasma lipids metabolism disorders.

2011-01-01

13

Alterations of high density lipoprotein subclasses in obese subjects  

Microsoft Academic Search

The object of this study was to investigate the characteristics of lipid metabolism in obese subjects, with particular emphasis\\u000a on the alteration of HDL subclass contents and distributions. A population of 581 Chinese individuals was divided into four\\u000a groups (25 underweight subjects, 288 of desirable weight, 187 overweight, and 45 obese) according to body mass index (BMI).\\u000a Apoprotein A-I (apoA-I)

Li Tian; Lianqun Jia; Mingde Fu; Ying Tian; Yanhua Xu; Haoming Tian; Yuye Yang

2006-01-01

14

Alterations of high density lipoprotein subclasses in obese subjects.  

PubMed

The object of this study was to investigate the characteristics of lipid metabolism in obese subjects, with particular emphasis on the alteration of HDL subclass contents and distributions. A population of 581 Chinese individuals was divided into four groups (25 underweight subjects, 288 of desirable weight, 187 overweight, and 45 obese) according to body mass index (BMI). Apoprotein A-I (apoA-I) contents of plasma HDL sub-classes were determined by 2-D gel electrophoresis associated with an immunodetection method. The concentrations of TG and the apoA-I content of pre-beta 1-HDL were significantly higher (P < 0.01 and P < 0.01, respectively), but the levels of HDL cholesterol, and the apoA-I contents of HDL2a and HDL2b were significantly lower (P < 0.01, P < 0.05, and P < 0.01, respectively) in obese subjects than in subjects having a desirable weight. Moreover, with the elevation of BMI, small-sized pre-beta 1-HDL increased gradually and significantly, whereas large-sized HDL2b decreased gradually and significantly. Meanwhile, the variations in HDL subclass distribution were more obvious with the elevation of TG levels in obese as well as overweight subjects. In addition, Pearson correlation analysis revealed that BMI and TG levels were positively correlated with pre-beta 1-HDL but negatively correlated with HDL2b. Multiple regression analysis also showed that TG concentrations were associated independently and positively with high pre-beta 1-HDL and independently and negatively with low HDL2b in obese and overweight subjects. The HDL particle size was smaller in obese and overweight subjects. The shift to smaller size was more obvious with the elevation of BMI and TG, especially TG levels. These observations, in turn, indicated that HDL maturation might be abnormal, and reverse cholesterol transport might be impaired. PMID:17120933

Tian, Li; Jia, Lianqun; Mingde, Fu; Tian, Ying; Xu, Yanhua; Tian, Haoming; Yang, Yuye

2006-08-01

15

Alterations in low-density lipoprotein and high-density lipoprotein subclasses among hispanic women with polycystic ovary syndrome: influence of insulin and genetic factors  

Microsoft Academic Search

Objective: To examine the influence of hyperandrogenism on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass levels as well as lipoprotein (a) levels in hyperandrogenic women compared with a control group.Design: Case-control study.Setting: University-based outpatient clinic.Patient(s): Sixteen Hispanic women with polycystic ovary syndrome were compared with 21 controls matched for age, weight, and ethnicity.Intervention(s): None.Main Outcome Measure(s): Fasting serum levels

Richard S Legro; Patricia Blanche; Ronald M Krauss; Rogerio A Lobo

1999-01-01

16

The relationship between high density lipoprotein subclass profile and plasma lipids concentrations  

Microsoft Academic Search

HDL particles posses multiple antiatherogenic activities and the identification and differentiation of individual HDL subclasses may be useful in documentation and understanding of metabolic changes of different HDL subclasses. The major plasma lipids exist and are transported in the form of lipoprotein complexes. Hence, alterations in plasma lipids levels can interfere with the composition, content, and distribution of plasma lipoprotein

Li Tian; Mingde Fu

2010-01-01

17

The Value and Distribution of High-Density Lipoprotein Subclass in Patients with Acute Coronary Syndrome  

PubMed Central

Background High-density lipoprotein (HDL) enhances cholesterol efflux from the arterial wall and exhibits potent anti-inflammatory and anti-atherosclerosis (AS) properties. Whether raised HDL levels will clinically benefit patients with acute coronary syndrome (ACS) and the value at which these effects will be apparent, however, is debatable. This study examined the HDL subclass distribution profile in patients with ACS. Methods Plasma HDL subclasses were measured in 158 patients with established ACS and quantified by two-dimensional gel electrophoresis and immunoblotting. ACS diagnosis was based on symptoms of cardiac ischemia, electrocardiogram (ECG) abnormalities, speciality cardiac enzyme change along with presence of coronary heart disease (CHD) on coronary angiography. Results The small-sized pre?1-HDL, HDL3b, and HDL3a levels were significantly higher, and the large-sized HDL2a and HDL2b levels were significantly lower in patients with ACS than in those with stable angina pectoris (SAP) and in normal control subjects. Meanwhile, with an elevation in the low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), body mass index (BMI), and blood pressure (BP), and the reduction in the high density lipoprotein cholesterol (HDL-C) levels, the HDL2b contents significantly decreased and the pre?1-HDL contents significantly increased in patients with ACS. The correlation analysis revealed that the apolipoprotein (apo)A-I levels were positively and significantly with all HDL subclasses contents; plasma total cholesterol (TC) and fasting plasma glucose (FPG) levels were inversely associated with HDL2a, and HDL2b. Moreover, the FPG levels were positively related to HDL3c, HDL3b, and HDL3a in ACS patients. Conclusion The HDL subclass distribution profile remodeling was noted in the patients with ACS. Plasma lipoprotein and FPG levels, BP, and BMI play an important role in the HDL subclass metabolism disorder for patients with ACS. The HDL subclass distribution phenotype might be useful as a novel biomarker to assist in the risk stratification of patients with ACS.

Tian, Li; Li, Chuanwei; Liu, Yinghui; Chen, Yucheng; Fu, Mingde

2014-01-01

18

Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women  

Microsoft Academic Search

To understand the mechanism responsible for ma- ternal hyperlipidemia, 25 healthy pregnant women were stud- ied longitudinally during the three trimesters of gestation and at post-partum, and 11 were studied again at post-lactation. Triglyceride and cholesterol levels increased with gestation in all the lipoprotein fractions. However, the greatest change appeared in low density (LDL) and high density (HDL) lipo- proteins,

J. J. Alvarez; A. Montelongo; A. Iglesias; M. A. Lasuncion; E. Herreral

19

Effect of combination nicotinic acid and gemfibrozil treatment on intermediate density lipoprotein, and subclasses of low density lipoprotein and high density lipoprotein in patients with combined hyperlipidemia.  

PubMed

The goal of this study was to determine, using analytic ultracentrifugation, the effect of nicotinic acid alone or nicotinic acid added to gemfibrozil on lipoprotein subclass distribution, including intermediate-density lipoprotein (IDL; low-density to very low density flotation rate [S(f)] 12 to 20); low-density lipoprotein (LDL) subfractions LDL-I (S(f) 7 to 12), LDL-II (S(f) 5 to 7), LDL-III (S(f) 3 to 5), and LDL-IV (S(f) 0 to 3); and high-density lipoprotein (HDL) subfractions HDL(2) (high-density flotation rate 3.5 to 9.0) and HDL(3) (high-density flotation rate 0 to 3.5). Patients with combined hyperlipidemia were randomized to nicotinic acid (1,500 mg/day) plus placebo or nicotinic acid plus gemfibrozil (1,200 mg/d) for 12 weeks. Baseline characteristics were similar between the 2 groups, and mean LDL cholesterol (180 +/- 33 mg/dl) and triglycerides (310 +/- 126 mg/dl) were typical for patients with combined hyperlipidemia. Treatment with nicotinic acid resulted in a reduction in dense LDL (S(f) 5 to 7; p = 0.02), which was counterbalanced by an increase in buoyant LDL (S(f) 7 to 12; p = 0.03) that resulted in no significant LDL mass or LDL cholesterol change. IDL was reduced (p = 0.005) and HDL(2) increased by 143% (p = 0.004). The combination of nicotinic acid and gemfibrozil resulted in a further 17.8% reduction in apolipoprotein B (p = 0.06), a further 33.8% reduction in IDL (p = 0.06), and a greater reduction in the apolipoprotein B/apolipoprotein A-I ratio (p = 0.02). The combination of nicotinic acid and gemfibrozil reduced atherogenic by IDL 71%, dense LDL-III by 52%, and apolipoprotein B by 37% and increased protective HDL(2) by 90%. In conclusion, this investigation revealed that a combination of a fibric acid derivative and nicotinic acid offers greater improvement in detailed lipoprotein subclass distribution and apolipoprotein ratios than monotherapy. PMID:19166694

Superko, H Robert; Garrett, Brenda C; King, Spencer B; Momary, Kathryn M; Chronos, Nicolas A; Wood, Peter D

2009-02-01

20

Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?  

PubMed Central

Background Some patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ?150 mg/dL. Results Both treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ?150 mg/dL. Conclusions When assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels. Trial Registration (Registered at clinicaltrials.gov: Clinical trial # NCT00276484)

2010-01-01

21

Increase in plasma high-density lipoprotein 2b subclass protein concentration after pravastatin treatment in patients with hypercholesterolemia  

Microsoft Academic Search

To determine the effects of pravastatin on plasma lipid levels, on low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle size and HDL subclass protein concentration, we studied 31 patients with hypercholesterolemia (9 men and 22 women, aged 36 to 79 years [mean age, 61.5 ± 10.3 years]). Patients were treated with pravastatin 10 mg daily for 12 weeks. After treatment,

Takeshi Hibino; Nagahiko Sakuma; Akihiko Yoneyama; Takaaki Sato; Takao Fujinami

1996-01-01

22

The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution  

PubMed Central

Objective To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. Methods Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. Results Contents of pre?1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, pre?1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of pre?1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ? 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. Conclusions The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of pre?1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.

2011-01-01

23

Association of the low-density lipoprotein cholesterol\\/high-density lipoprotein cholesterol ratio and concentrations of plasma lipids with high-density lipoprotein subclass distribution in the Chinese population  

Microsoft Academic Search

BACKGROUND: To evaluate the relationship between the low-density lipoprotein cholesterol (LDL-C)\\/high-density lipoprotein cholesterol (HDL-C) ratio and HDL subclass distribution and to further examine and discuss the potential impact of LDL-C and HDL-C together with TG on HDL subclass metabolism. RESULTS: Small-sized pre?1-HDL, HDL3b and HDL3a increased significantly while large-sized HDL2a and HDL2b decreased significantly as the LDL-C\\/HDL-C ratio increased. The

Li Tian; Yinghui Liu; Yang Qin; Shiyin Long; Yanhua Xu; Mingde Fu

2010-01-01

24

The relationship between high density lipoprotein subclass profile and plasma lipids concentrations.  

PubMed

HDL particles possess multiple antiatherogenic activities and the identification and differentiation of individual HDL subclasses may be useful in documentation and understanding of metabolic changes of different HDL subclasses. The major plasma lipids exist and are transported in the form of lipoprotein complexes. Hence, alterations in plasma lipids levels can interfere with the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. The research review major discussed the relationship between plasma lipids levels and HDL subclasses distribution. The general shift toward smaller size of HDL particle size in HTG, HCL and MHL subjects, and the changes were more prominent with the elevation of TG and TC levels which imply that HDL maturation might be abnormal and RCT pathway might be weaken, and these changes were more seriously in MHL subjects. Plasma contents of small sized HDL particles significantly higher, whereas those of large sized HDL particles were significantly lower with elevation of TG/HDL-C and TC/HDL-C ratios. Increased in the TC/HDL-C ratio alone did not influence the distributions of HDL subclasses significantly when the TG/HDL-C ratio was low (TG/HDL-C ? 2.5). Hence, the TG/HDL-C ratio might be more sensitive to reflect the alteration of HDL subclass distribution than the TC/HDL-C ratio. In LDL-C/HDL-C ? 2.3 group, the pattern of distribution in HDL subclass was in agreement with the normolipidemic subjects. Moreover, considering the relative ease of measuring TC/HDL-C, TG/HDL-C and LDL-C/HDL-C ratios, as opposed to measuring HDL subclasses, these 3 ratios together may be a good indicator of HDL subclass distribution. The protective effect of increased apoA-I levels against the reduction of HDL(2b) caused by elevated TG concentration. On one hand, plasma HDL-C and apoA-I appear to play a coordinated role in the assembly of HDL particles and the determination of their contents among the total subjects. On the other hand, the apoA-I level might be a more powerful factor than HDL-C to influence the distribution of HDL subclasses in hyperlipidemic subjects. At the same time, from point of HDL subclasses distribution, the plasma lipids, apos concentrations and apos ratios should be considered while assessing the CHD risk. Abnormality of HDL subclasses distribution may result in accelerated atherosclerosis, therapeutic normalization of attenuated antiatherogenic HDL function in terms of both particle number and distribution of HDL particles is the target of innovative pharmacological approaches to large-sized HDL particles rising, including enhanced apoA-I levels. PMID:20950490

Tian, Li; Fu, Mingde

2010-01-01

25

The relationship between high density lipoprotein subclass profile and plasma lipids concentrations  

PubMed Central

HDL particles posses multiple antiatherogenic activities and the identification and differentiation of individual HDL subclasses may be useful in documentation and understanding of metabolic changes of different HDL subclasses. The major plasma lipids exist and are transported in the form of lipoprotein complexes. Hence, alterations in plasma lipids levels can interfere with the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. The research review major discussed the relationship between plasma lipids levels and HDL subclasses distribution. The general shift toward smaller size of HDL particle size in HTG, HCL and MHL subjects, and the changes were more prominent with the elevation of TG and TC levels which imply that HDL maturation might be abnormal and RCT pathway might be weaken, and these changes were more seriously in MHL subjects. Plasma contents of small sized HDL particles significantly higher, whereas those of large sized HDL particles were significantly lower with elevation of TG/HDL-C and TC/HDL-C ratios. Increased in the TC/HDL-C ratio alone did not influence the distributions of HDL subclasses significantly when the TG/HDL-C ratio was low (TG/HDL-C ? 2.5). Hence, the TG/HDL-C ratio might be more sensitive to reflect the alteration of HDL subclass distribution than the TC/HDL-C ratio. In LDL-C/HDL-C ? 2.3 group, the pattern of distribution in HDL subclass was in agreement with the normolipidemic subjects. Moreover, considering the relative ease of measuring TC/HDL-C, TG/HDL-C and LDL-C/HDL-C ratios, as opposed to measuring HDL subclasses, these 3 ratios together may be a good indicator of HDL subclass distribution. The protective effect of increased apoA-I levels against the reduction of HDL2b caused by elevated TG concentration. On one hand, plasma HDL-C and apoA-I appear to play a coordinated role in the assembly of HDL particles and the determination of their contents among the total subjects. On the other hand, the apoA-I level might be a more powerful factor than HDL-C to influence the distribution of HDL subclasses in hyperlipidemic subjects. At the same time, from point of HDL subclasses distribution, the plasma lipids, apos concentrations and apos ratios should be considered while assessing the CHD risk. Abnormality of HDL subclasses distribution may result in accelerated atherosclerosis, therapeutic normalization of attenuated antiatherogenic HDL function in terms of both particle number and distribution of HDL particles is the target of innovative pharmacological approaches to large-sized HDL particles rising, including enhanced apoA-I levels.

2010-01-01

26

Small, dense low-density lipoprotein subclass pattern B: Issues for the clinician  

Microsoft Academic Search

A large portion of coronary artery disease (CAD) can be attributed to disorders of lipoprotein metabolism. However, these\\u000a disorders are a complex interaction of genetic susceptibility and environmental interaction. The most common disorder of lipoprotein\\u000a metabolism contributing to CAD is the Small, Dense Low-Density Lipoprotein Pattern B disorder, also known as the Atherogenic\\u000a Lipoprotein Profile (ALP), which consists of multiple

H. Robert Superko

1999-01-01

27

Effect of Estrogen on Very Low Density Lipoprotein and Low Density Lipoprotein Subclass Metabolism in Postmenopausal Women  

Microsoft Academic Search

Estrogen decreases low density lipoprotein (LDL) particle size, and smaller LDL particles are associated with coronary atherosclerosis. To understand the metabolic basis for this change, we studied the effect of oral 17b-estradiol (2 mg\\/day) on apolipoprotein B-100 (apoB) metabolism, in eight healthy postmenopausal women. The study was a randomized, double blinded, placebo-controlled, cross-over trial with intervention sequences of 6 weeks

HANNIA CAMPOS; BRIAN W. WALSH; HELENA JUDGE; FRANK M. SACKS

2010-01-01

28

Identification of multiple subclasses of plasma low density lipoproteins in normal humans  

Microsoft Academic Search

Density gradient ultracentrifugation of low density lipoproteins (LDL) from 12 normal subjects showed multiple, distinct isopycnic bands. Each band could be assigend to one of four density intervals and the boundaries of these intervals were consistent among all the subjects. Analytic ultracentrifuge flotation (S\\/sub f\\/°) rates were assigned to the four density intervals, and there was a strong correlation between

Ronald M. Krauss; David J. Burke

1982-01-01

29

High-density lipoprotein subclass and particle size in coronary heart disease patients with or without diabetes  

PubMed Central

Background A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes. Methods Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection. Results Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL2b+pre?2, and HDL2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The pre?1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL2a, and HDL2b+pre?2. Conclusions The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.

2012-01-01

30

Low density lipoprotein subclasses and response to a low-fat diet in healthy men  

SciTech Connect

Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-fat, 87 subjects had predominantly large, buoyant LDL as measured by gradient gel electrophoresis and confirmed by analytic ultracentrifugation (pattern A), while the remainder had primarily smaller, denser LDL (pattern B). On low-fat, 36 men changed from pattern A to B. Compared with the 51 men in the stable A group, men in the stable B group (n = 18) had a three-fold greater reduction in LDL cholesterol and significantly greater reductions in plasma apoB and mass of intermediate (LDL II) and small (LDL III) LDL subtractions measured by analytic ultracentrifugation. In both stable A and change groups, reductions in LDL-cholesterol were not accompanied by reduced plasma apoB, consistent with the observation of a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, without significant change in particle number. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in response to a low-fat diet.

Krauss, R.M.; Dreon, D.M. [Lawrence Berkeley Lab., CA (United States). Life Sciences Div.

1994-11-01

31

Association of the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and concentrations of plasma lipids with high-density lipoprotein subclass distribution in the Chinese population  

PubMed Central

Background To evaluate the relationship between the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and HDL subclass distribution and to further examine and discuss the potential impact of LDL-C and HDL-C together with TG on HDL subclass metabolism. Results Small-sized pre?1-HDL, HDL3b and HDL3a increased significantly while large-sized HDL2a and HDL2b decreased significantly as the LDL-C/HDL-C ratio increased. The subjects in low HDL-C level (< 1.03 mmol/L) who had an elevation of the LDL-C/HDL-C ratio and a reduction of HDL2b/pre?1-HDL regardless of an undesirable or high LDL-C level. At desirable LDL-C levels (< 3.34 mmol/L), the HDL2b/pre?1-HDL ratio was 5.4 for the subjects with a high HDL-C concentration (? 1.55 mmol/L); however, at high LDL-C levels (? 3.36 mmol/L), the ratio of LDL-C/HDL-C was 2.8 in subjects, and an extremely low HDL2b/pre?1-HDL value although with high HDL-C concentration. Conclusion With increase of the LDL-C/HDL-C ratio, there was a general shift toward smaller-sized HDL particles, which implied that the maturation process of HDL was blocked. High HDL-C concentrations can regulate the HDL subclass distribution at desirable and borderline LDL-C levels but cannot counteract the influence of high LDL-C levels on HDL subclass distribution.

2010-01-01

32

Associations of genotypes at the apolipoprotein AI-CIII-AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses.  

PubMed

Association studies were carried out in a sample of 86 patients from Sweden who had survived a myocardial infarction (MI) at a young age and 93 age-matched healthy individuals, to compare the impact of polymorphisms at the apolipoprotein (apo) AI-CIII-AIV gene cluster on among-individual differences in plasma lipid and lipoprotein traits, the five high density lipoprotein (HDL) subclasses (2b to 3c), lipoprotein lipase (LPL) activity and presence and progression of atherosclerosis. Individuals were genotyped for four polymorphisms; 5'apoAI (G/A-75), 3'apoAI (PstI; P +/-), apoCIII (C/T1100) and apoCIII (PvuII; V +/-), using PCR-based techniques. Allele frequencies were similar in healthy individuals and patients (frequencies of alleles in combined population: 5'apoAI-A-75 = 0.14, 3'apoAI-P- = 0.05, apoCIII-T1100 = 0.27 and apoCIII-V- = 0.18). In the healthy individuals, levels of low density lipoprotein (LDL) triglycerides were significantly associated with genotypes of the apoCIII-PvuII polymorphism (p = 0.02), but no other associations were found between lipids or HDL subclasses and single polymorphisms in the apoAI-CIII-AIV gene cluster. Levels of triglycerides and very low density lipoprotein (VLDL) triglycerides were significantly higher in the presence of the haplotype defined by the presence of apoCIII-T1100 and common alleles of the other three polymorphisms, explaining 5.8% and 7.8% (p = 0.03 and 0.01), respectively, of sample variance. In the patients, no associations were found between lipids or HDL subclasses and variation at the apoAI-CIII-AIV gene cluster. Associations were also examined between levels of HDL subclasses and variation at the apoE (common isoforms), apoB (signal peptide and XbaI polymorphisms) and lipoprotein lipase (PvuII, HindIII and Serine447/Stop polymorphisms) gene loci. In the patient group only, levels of protein in HDL2b, HDL2a and HDL3b subclasses were significantly associated with genotypes of the LPL-HindIII polymorphism (22.1, 19.3 and 11.4%, respectively, of sample variance; p < 0.05). Finally, associations were examined between genotypes at the apoAI-CIII-AIV gene cluster and the extent of coronary atherosclerosis. Global severity of atherosclerosis at the first angiography was weakly associated with genotypes of the apoCIII-C/T1100 polymorphism, presence of the T1100 allele being associated with 53% lower median score (1.6 vs 0.75; p = 0.09).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7834891

Peacock, R E; Hamsten, A; Johansson, J; Nilsson-Ehle, P; Humphries, S E

1994-10-01

33

Relation of cholesterol esterification rate to the plasma distribution of high-density lipoprotein subclasses in normal and hypertensive women.  

PubMed

We studied the particle size distribution of plasma high-density lipoproteins (HDL) by gradient gel electrophoresis and by assay of cholesterol esterification rate (FERHDL) in plasma depleted of very low (VLDL) and low-density (LDL) lipoproteins in 32 hypertensive women (53 +/- 10 y old) and in an age-matched group of 21 apparently healthy women. There were no significant differences between the groups with respect to their plasma total, HDL- and LDL-cholesterol. The plasma triglyceride (TG) concentration was significantly higher in the group of hypertensive women, and HDL-free cholesterol was significantly lower in the hypertensive group. There were highly significantly differences in the relative proportions of HDL subclasses between the hypertensive and control women: HDL2b was significantly lower and HDL3b,c was significantly higher in hypertensive patients compared to controls. FERHDL was 12 +/- 4%/h in the control group and 18 +/- 6%/h in patients with hypertension (p < 0.001). There was a strong positive correlation between FERHDL and the relative content of HDL3b,c, and a strong negative correlation between FERHDL and HDL2b in both groups. Comparison of subgroups of healthy and hypertension pre- and postmenopausal women revealed, apart from age, no significant differences between the healthy subjects in any of the above parameters. PMID:8714788

Dobiásová, M; Stríbrná, J; Frohlich, J J

1995-12-01

34

The relationship between high density lipoprotein subclass profile and apolipoprotein concentrations.  

PubMed

The HDL fraction in human plasma is heterogeneous in terms of size, shape, composition, and surface charge. The HDL subclasses contents were quantified by 2-dimensional non-denaturing gel electrophoresis, immunoblotting, and image analysis. This research review systematically analyzed the relationship between the contents of HDL subclasses and the concentrations and ratios of the 5 major plasma apolipoproteins (apo). As the concentration of apoA-I increases, the contents of all HDL subclasses increase significantly. The most significant association was observed between large-sized HDL2b contents and apoA-I. ApoA-II played a dual function in the contents of HDL subclasses, and both small-sized HDL3b and HDL3a and large-sized HDL2b tended to increase with apoA-II concentration. An increase in the concentrations of apoC-II, C-III, and B-100 resulted in higher levels of small-sized HDL particles and lower levels of large-sized HDL particles. Plasma apoB- 100, apoC-II, and apoC-III appear to play a coordinated role in assembly of HDL particles and the determination of their contents. Higher concentrations of apoA-I could inhibit the reduction in content of large-sized HDL2b effected by apoB-100, C-II, and C-III. The pre?1-HDL contents increased significantly and those of HDL2b declined progressively with an increased apoB-100/apoA-I or a decreased apoC-III/apoC-II ratio. In summary, each apo has distinct but interrelated roles in HDL particle generation and metabolism. ApoA-I and apoC-II concentrations are independent determinants of HDL subtypes in circulation and apoA-I levels might be a more powerful factor to influence HDL subclasses distribution. Moreover, apoB- 100/apoA-I ratio could reliably and sensitively reflect the HDL subclass profile. PMID:21747218

Tian, L; Fu, M

2011-06-01

35

Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses.  

PubMed

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of age, adiposity, alcohol intake, and exogenous estrogen with high-density lipoprotein (HDL) subclasses in 427 members of 51 principally Mormon kindreds. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 mm). Age and alcohol intake were obtained from questionnaires, and body mass index was computed from clinic measurements as weight (kg)/height (m)2. The results suggest that HDL3b concentrations were higher after menopause than before. Adult men (> or = 18 years old) had significantly higher HDL3c and HDL3b and significantly lower HDL2b and HDL2a levels than younger boys. Compared with the women, adult men had higher levels of HDL3c and HDL3b and lower levels of HDL2b, HDL2a, and larger-diameter HDL3a particles. There were no significant differences between the HDL profiles of women and younger boys, suggesting that divergence in HDL occurs during puberty. Eighty-eight percent of the increase in HDL associated with estrogen replacement in postmenopausal women occurred within HDL3a and HDL2a. Reported alcohol intake in adult men correlated with two HDL regions: one within the HDL2b region and a second within the HDL3a/2a region, whereas in women the positive correlation between alcohol and HDL levels was within the HDL2b region only. In both men and premenopausal adult women, increasing levels of body mass index were associated with higher levels of HDL3b and lower levels of HDL2b.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8218107

Williams, P T; Vranizan, K M; Austin, M A; Krauss, R M

1993-11-01

36

The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: The stanford coronary risk intervention project baseline survey  

Microsoft Academic Search

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was

Paul T. Williams; William L. Haskell; Karen M. Vranizan; Ronald M. Krauss

1995-01-01

37

Association between moderately oxidized low-density lipoprotein and high-density lipoprotein particle subclass distribution in hemodialyzed and post-renal transplant patients*  

PubMed Central

Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman’s rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=?0.306, P=0.012), LDL-C (R=?0.283, P=0.020), and non-HDL-C (R=?0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-?-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.

Kimak, Elzbieta; Halabis, Magdalena; Baranowicz-Gaszczyk, Iwona; Solski, Janusz; Ksiazek, Andrzej

2011-01-01

38

Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A? in subjects with prediabetes.  

PubMed

Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels <100 mg/dL (all p < 0.05). The proportion of small HDL3 over HDL cholesterol (HDL-C) was significantly increased in prediabetic subjects compared with their controls (p < 0.05). The activity of the anti-atherogenic HDL-associated lipoprotein-associated phospholipase A? (HDL-LpPLA?) was significantly lower in subjects with prediabetes (p < 0.05), whereas the activity of paraoxonase 1 (using both paraoxon and phenyl acetate as substrates) did not significantly differ between subjects with or without prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA?. PMID:23546765

Filippatos, Theodosios D; Rizos, Evangelos C; Tsimihodimos, Vasilios; Gazi, Irene F; Tselepis, Alexandros D; Elisaf, Moses S

2013-06-01

39

Relation of Lipoprotein Subclasses as Measured by Proton Nuclear Magnetic Resonance Spectroscopy to Coronary Artery Disease  

Microsoft Academic Search

Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL),

David S. Freedman; James D. Otvos; Elias J. Jeyarajah; Joseph J. Barboriak; Alfred J. Anderson; John A. Walker

40

Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the pravastatin limitation of atherosclerosis in the coronary arteries (PLAC-I) trial  

Microsoft Academic Search

Lipoprotein subclass measurements may enhance the prediction of coronary artery disease (CAD) risk, but clinical application of such information has been hindered by the relatively laborious and time-consuming nature of laboratory measurement methods. In this study, lipoprotein subclass analyses were performed on frozen plasma samples from 241 participants in the Pravastatin Limitation of Atherosclerosis in the Coronary arteries Trial using

Robert S Rosenson; James D Otvos; David S Freedman

2002-01-01

41

High-density lipoprotein subclasses and esterification rate of cholesterol in children: effect of gender and age.  

PubMed

Since the development of coronary heart disease (CAD) is affected by a specific pattern of plasma high density lipoprotein (HDL) effects it may be useful to know whether this occurs already in childhood. In this study we evaluated particle size distribution of HDL by gradient gel electrophoresis and the determination of cholesterol esterification rate (FER(HDL)) in plasma depleted of apo B lipoproteins in 221 children (108 boys and 113 girls) aged 4 months to 20 years. Total plasma- (TC), low-density lipoprotein- (LDL-C) and HDL- (HDL-C) cholesterol, HDL unesterified cholesterol (HDL-UC) and plasma triglycerides (TG) were also measured. There were no significant gender and age differences with respect to the plasma TC, LDL-TC and TG but concentration of HDL-TC increased with age. Post-pubertal girls had significantly higher relative concentrations of HDL2b compared to boys (30.4% vs 17.2%), while HDL3b,c was lower in post-pubertal girls (8.7% vs. 16.5%). FER(HDL) correlated inversely with HDL2b and positively with HDL3b,c particles and was significantly higher in boys of the post-pubertal group compared to girls (16.9%/h vs 12.5%/h). While in girls there was a positive correlation between age and HDL-C, HDL-UC and the relative concentration of HDL2b no significant correlation were observed in boys. In girls the increase in TC showed a significant correlation with a simultaneous increase in HDL-C, HDL-UC and HDL2b. In boys TC correlated significantly with changes in TG only. When HDL2b and HDL3b,c cholesterol levels are calculated from HDL-C concentration and per cent distribution the differences between males and females are further emphasized. These data indicate that HDL particle size distribution is age- and gender-dependent. PMID:9764883

Dobiásová, M; Urbanová, Z; Rauchová, H; Samánek, M; Frohlich, J J

1998-09-01

42

Effects of Lipid-Lowering Drugs on High-Density Lipoprotein Subclasses in Healthy Men--A Randomized Trial  

PubMed Central

Context and Objective Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution. Design and Participants A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l) and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l). They were treated with ezetimibe (10 mg/day, n?=?24), simvastatin (40 mg/day, n?=?24) or their combination (n?=?24) for 14 days. Blood was drawn before and after the treatment period. HDL subclasses were determined using polyacrylamide gel-tube electrophoresis. Multivariate regression models were used to determine the influence of treatment and covariates on changes in HDL subclass composition. Results Baseline HDL subclasses consisted of 33±10% large, 48±6% intermediate and 19±8% small HDL. After adjusting for baseline HDL subclass distribution, body mass index, LDL-C and the ratio triglycerides/HDL-C, there was a significant increase in large HDL by about 3.9 percentage points (P<0.05) and a decrease in intermediate HDL by about 3.5 percentage points (P<0.01) in both simvastatin-containing treatment arms in comparison to ezetimibe. The parameters obtained after additional adjustment for the decrease in LDL-C indicated that about one third to one half of these effects could be explained by the extent of LDL-C-lowering. Conclusions In healthy men, treatment with simvastatin leads to favorable effects on HDL subclass composition, which was not be observed with ezetimibe. Part of these differential effects may be due to the stronger LDL-C-lowering effects of simvastatin. Trial Registration ClinicalTrials.gov NCT00317993

Spenrath, Nadine; Montalto, Giuseppe; Krone, Wilhelm; Gouni-Berthold, Ioanna

2014-01-01

43

Small, dense, low-density lipoprotein and atherosclerosis  

Microsoft Academic Search

Disorders of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclass distribution are more common contributors\\u000a to coronary artery disease (CAD) than is elevated low-density lipoprotein cholesterol (LDLC). Recent research has emphasized\\u000a the importance of LDL and HDL subclass distribution in patient management and response to treatments. Laboratory determination\\u000a of LDL and HDL subclass distribution involves analytic ultracentrifugation or polyacrylalmide gradient

H. Robert Superko

2000-01-01

44

The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B  

SciTech Connect

To better define the role of environmental factors on LDL phenotypic expression, the authors determined LDL patterns in patients with acquired immunodeficiency syndrome (AIDS), and infection characterized by hypertriglyceridemia and weight loss. Similar to previous studies, plasma triglyceride levels were increased, whereas plasma cholesterol, LDL cholesterol, and HDL cholesterol levels were decreased in the AIDS subjects compared to those in age-matched controls. The percentage of AIDS subjects with the LDL B phenotype was increased 2.5-fold, demonstrating an increased prevalence of the LDL B phenotype in an acquired form of hypertriglyceridemia. For each LDL phenotype in AIDS, serum triglyceride levels were higher than the same phenotypic pattern in controls, with the most marked elevations in triglycerides found in AIDS subjects with the LDL B phenotype. In contrast to what was observed in controls, HDL cholesterol levels were decreased in all AIDS subjects and were unrelated to LDL pattern. Total and LDL cholesterol levels were higher in controls with the LDL B phenotype than in those with the LDL A phenotype, but there was no difference in total and LDL cholesterol in AIDS subjects with LDL B compared to A. On multiple regression analysis in subjects with AIDS, plasma triglyceride levels, age, and HDL cholesterol all contribute to the occurrence of the LDL B phenotype, but elevations in plasma triglyceride levels are the strongest independent predictor. Body mass index was not a predictor of LDL B phenotype in AIDS. These results suggest that disturbances in triglyceride metabolism that are caused by AIDS lead to the appearance of the LDL subclass B phenotype and provide further evidence that environmental or disease states that perturb lipid metabolism can produce an increased prevalence of the LDL B phenotype. 35 refs., 1 fig., 5 tabs.

Feingold, K.R.; Krauss, R.M.; Pang, M.; Doerrler, W.; Jensen, P.; Grunfeld, C. (Univ. of California, San Francisco (United States) Lawrence Berkeley Lab., CA (United States))

1993-06-01

45

High-density lipoprotein subclasses distribution and composition in Mexican adolescents with low HDL cholesterol and\\/or high triglyceride concentrations, and its association with insulin and c-reactive protein  

Microsoft Academic Search

We tested whether low high-density lipoprotein cholesterol (HDL-C) and\\/or high triglycerides are associated to abnormal HDL subclasses distribution and composition, and their relationships with fasting insulin and C-reactive protein (CRP). Four groups of adolescents were studied: group 1 (HDL-C?35mg\\/dl+TG?150mg\\/dl; n=16); group 2 (isolated HDL-C?35mg\\/dl; n=31); group 3 (isolated TG?150mg\\/dl; n=20); and group 4 (CT<200mg\\/dl, HDL-C>35mg\\/dl, LDL-C<130mg\\/dl, and TG<150mg\\/dl; n=39). Tanner

Aida Medina-Urrutia; Juan G. Juarez-Rojas; Rocio Martínez-Alvarado; Esteban Jorge-Galarza; Rosalinda Posadas-Sánchez; Guillermo Cardoso-Saldaña; Enrique Mendoza-Perez; Carlos Posadas-Romero

2008-01-01

46

Sleep Apnea Is Related to the Atherogenic Phenotype, Lipoprotein Subclass B  

PubMed Central

Study Objectives: Sleep apnea has been implicated as an independent risk factor for atherosclerotic coronary artery disease (CAD). An association between the severity of sleep apnea and total cholesterol levels has previously been reported. However, the association with small dense low density lipoprotein (LDL) cholesterol concentration (subclass B), one of the strongest predictors of atherosclerosis, is unknown. We examined the relationship between sleep apnea and LDL subclass B, considering body size. Methods: This is a cross-sectional observational cohort of participants enrolled in a cardiovascular health study. Sleep apnea was assessed with a validated portable monitor. Lipid panels included total cholesterol, triglycerides, high density lipoprotein cholesterol, LDL cholesterol, and LDL subclasses A, B, and A/B. Sleep apnea was analyzed categorically using the apnea hypopnea index (AHI). Results: A total of 519 participants were evaluated. Mean age was 58.7 ± 7.4 years; BMI was 29.6 ± 5.7; 65% were female; 59% were Caucasian, and 37% were African American. Among participants with abnormal waist circumference by ATP III criteria, moderate to severe sleep apnea (AHI ? 25) was not independently associated with LDL subclass B. In contrast, among participants with normal waist circumference, moderate to severe sleep apnea was associated with 4.5-fold odds of having LDL subclass B. Conclusions: Sleep apnea is independently associated with an atherogenic phenotype (LDL subclass B) in non-obese individuals. The association between sleep apnea and LDL subclass B in those with normal waist circumference may account, in part, for the increased risk of atherosclerosis and subsequent vascular events. Citation: Luyster FS; Kip KE; Drumheller OJ; Rice TB; Edmundowicz D; Matthews K; Reis SE; Strollo PJ. Sleep apnea is related to the atherogenic phenotype, lipoprotein subclass B. J Clin Sleep Med 2012;8(2):155-161.

Luyster, Faith S.; Kip, Kevin E.; Drumheller, Oliver J.; Rice, Thomas B.; Edmundowicz, Daniel; Matthews, Karen; Reis, Steven E.; Strollo, Patrick J.

2012-01-01

47

Effects of extended-release niacin on lipoprotein subclass distribution  

Microsoft Academic Search

The efficacy of extended-release niacin (niacin ER) on lipoprotein subclasses was evaluated in patients with primary hypercholesterolemia using a proton nuclear magnetic resonance method. Paired plasma samples collected at baseline and after 12 weeks’ treatment with niacin ER 1,000 (n = 21) or 2,000 (n = 20) mg\\/day or placebo (n = 19) were available for 60 eligible patients from

John M Morgan; David M Capuzzi; Ronnie I Baksh; Charles Intenzo; Christina M Carey; Dana Reese; Kalen Walker

2003-01-01

48

Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy  

PubMed Central

Background Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients. Results The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications. Conclusion In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

Decewicz, David J; Neatrour, David M; Burke, Amy; Haberkorn, Mary Jane; Patney, Heather L; Vernalis, Marina N; Ellsworth, Darrell L

2009-01-01

49

Expression of Human Apoliprotein AI in Transgenic Mice Results in Reduced Plasma Levels of Murine Apolipoprotein AI and the Appearance of Two New High Density Lipoprotein Size Subclasses  

Microsoft Academic Search

In Western societies high density lipoprotein (HDL) levels correlate inversely with the risk for coronary heart disease. The primary protein component of both human and mouse HDL is apolipoprotein A-I (apoAI), which comprises >70% of HDL protein and 30% of HDL mass. Human HDLs include particles of several distinct size subpopulations, whereas HDLs from inbred C57BL\\/6 mice contain a single

Edward M. Rubin; Brian Y. Ishida; Shirley M. Clift; Ronald M. Krauss

1991-01-01

50

The associations of high-density lipoprotein subclasses with insulin and glucose levels, physical activity, resting heart rate, and regional adiposity in men with coronary artery disease: the Stanford Coronary Risk Intervention Project baseline survey.  

PubMed

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). HDL peak diameter was determined from the predominant peak of the HDL particle distribution when plotted against particle diameter. Four men who were non-insulin-dependent diabetics as defined by a fasting glucose exceeding 140 mg/dL had significantly higher plasma HDL3b levels and significantly smaller HDL peak diameters than nondiabetic men, and were therefore excluded from further analyses. In the remaining 93 nondiabetic men, plasma HDL3b levels correlated positively with indices of truncal obesity (waist to hip ratio and subscapular skinfold), whereas plasma HDL2b levels correlated negatively with indices of total adiposity (body mass index [BMI]) and truncal obesity (subscapular and abdominal skinfold). Fasting plasma insulin levels correlated negatively with HDL3a, HDL2a, and HDL2b. Obesity significantly affected the relationships of resting heart rate with insulin and HDL subclasses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7854154

Williams, P T; Haskell, W L; Vranizan, K M; Krauss, R M

1995-01-01

51

The Associations of High-Density Lipoprotein Subclasses With Insulin and Glucose Levels, Physical Activity, Resting Heart Rate, and Regional Adiposity in Men With Coronary Artery Disease: The Stanford Coronary Risk Intervention Project Baseline Survey  

PubMed Central

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2 to 7.8 nm), HDL3b (7.8 to 8.2 nm), HDL3a (8.2 to 8.8 nm), HDL2a (8.8 to 9.7 nm), and HDL2b (9.7 to 12 nm). HDL peak diameter was determined from the predominant peak of the HDL particle distribution when plotted against particle diameter. Four men who were non-insulin-dependent diabetics as defined by a fasting glucose exceeding 140 mg/dL had significantly higher plasma HDL3b levels and significantly smaller HDL peak diameters than nondiabetic men, and were therefore excluded from further analyses. In the remaining 93 nondiabetic men, plasma HDL3b levels correlated positively with indices of truncal obesity (waist to hip ratio and subscapular skinfold), whereas plasma HDL2b levels correlated negatively with indices of total adiposity (body mass index [BMI]) and truncal obesity (subscapular and abdominal skinfold). Fasting plasma insulin levels correlated negatively with HDL3a, HDL2a, and HDL2b. Obesity significantly affected the relationships of resting heart rate with insulin and HDL subclasses. In heavier men (BMI > 25.8 kg/m2) but not in the less-obese men (BMI < 25.8 kg/m2), resting heart rate was negatively correlated with HDL3a, HDL2a, and HDL2b levels and HDL peak diameter and positively correlated with fasting plasma insulin concentrations. Although the reported physical activity in heavier men also correlated with HDL3a, HDL2a, and resting heart rate, the associations of resting heart rate with HDL3a, HDL2a, and HDL2b could not be attributed to activity level. These analyses suggest that the influences of plasma insulin, regional adiposity, physical activity, and resting heart rate on HDL involve specific HDL subclasses. In the presence of increased adiposity, sympathetic drive and physical inactivity may reduce levels of larger HDL and the peak diameter of the major HDL subspecies.

Williams, Paul T.; Haskell, William L.; Vranizan, Karen M.; Krauss, Ronald M.

2010-01-01

52

The inherent accuracy of 1H NMR spectroscopy to quantify plasma lipoproteins is subclass dependent  

Microsoft Academic Search

Proton NMR spectroscopy as a means to quantify lipoprotein subclasses has received wide clinical interest. The experimental part is a fast routine procedure that contrasts favourably to other lipoprotein measurement protocols. The difficulties in using 1H NMR, however, are in uncovering the subclass specific information from the overlapping data. The NMR-based quantification has been evaluated only in relation to biochemical

Mika Ala-Korpela; Niko Lankinen; Aino Salminen; Teemu Suna; Pasi Soininen; Reino Laatikainen; Petri Ingman; Matti Jauhiainen; Marja-Riitta Taskinen; Károly Héberger; Kimmo Kaski

2007-01-01

53

Cholesterol esterification rate in plasma depleted of very low and low density lipoproteins is controlled by the proportion of HDL2 and HDL3 subclasses: study in hypertensive and normal middle-aged and septuagenarian men  

Microsoft Academic Search

The relationship between the fractional rate of cholesterol esterification (FERHDL) in very low density lipoprotein (VLDL)- and low density lipoprotein (LDL) - depleted plasma and the particle size distribution of high density lipoproteins (HDL) were studied in: u) a control group of 9 ap- parently healthy men (42 f 11 years); b) 15 septuagenarians (76 f 6 years) who had

Milada Dobiasova; Jarmila Stribrna; P. Haydn Pritchard; Jiri J. Frohlich

54

Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses.  

PubMed Central

In Western societies high density lipoprotein (HDL) levels correlate inversely with the risk for coronary heart disease. The primary protein component of both human and mouse HDL is apolipoprotein A-I (apoAI), which comprises greater than 70% of HDL protein and 30% of HDL mass. Human HDLs include particles of several distinct size subpopulations, whereas HDLs from inbred C57BL/6 mice contain a single population of particles. To study the regulation of apoAI expression and its role in HDL assembly, we created transgenic C57BL/6 mice containing the human apoAI gene. Two independent lines of transgenic mice with approximately twice the normal plasma levels of total apoAI were studied. The level of mouse apoAI is reduced greater than 4-fold in both transgenic lines, comprising only 4% of total plasma apoAI levels in one transgenic line and 13% in the other. We demonstrate that the mechanism responsible for the decrease in mouse apoAI is posttranscriptional. Parallel to the replacement of mouse with human apoAI, the single HDL species normally present in the plasma of C57BL/6 is replaced by two HDL subclasses similar in size to human HDL2b and HDL3a. The changes in murine apolipoprotein levels and HDL subclass size are inherited by all transgenic offspring of the two founder animals. These results suggest a dominant role of apoAI in determining the HDL particle size distribution and a mechanism involving expression of human apoAI transgenes that alters the plasma levels of mouse apoAI. Images

Rubin, E M; Ishida, B Y; Clift, S M; Krauss, R M

1991-01-01

55

Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses  

SciTech Connect

In Western societies high density lipoprotein (HDL) levels correlate inversely with the risk for coronary heart disease. The primary protein component of both human and mouse HDL is apolipoprotein A-I (apoAI), which comprises {gt}70% of HDL protein and 30% of HDL mass. Human HDLs include particles of several distinct size subpopulations, wheras HDLs from inbred C57BL/6 mice contain a single population of particles. To study the regulation of apoAI expression and its role in HDL assembly, we created transgenic C57BL/6 mice containing the human apoAI gene. Two independent lines of transgenic mice with approximately twice the normal plasma levels of total apoAI were studied. The level of mouse apoAI is reduced {gt}4-fold in both transgenic lines, comprising only 4% of total plasma apoAI levels in one transgenic line and 13% in the other. The authors demonstrate that the mechanism responsible for the decrease in mouse apoAI is posttranscriptional. Parallel to the replacement of mouse with human apoAI, the single HDL species normally present in the plasma of C57BL/6 is replaced by two HDL subclasses similar in size to human HDL{sub 2b} and HDL{sub 3a}. The changes in murine apolipoprotein levels and HDL subclass size are inherited by all transgenic offspring of the two founder animals. These results suggest a dominant role of apoAI in determining the HDL particle size distribution and a mechanism involving expression of human apoAI transgenes that alters the plasma levels of mouse apoAI.

Rubin, E.M.; Ishida, B.Y.; Clift, S.M.; Krauss, R.M. (Lawrence Berkeley Lab., CA (United States))

1991-01-15

56

Sex and Age Differences in Lipoprotein Subclasses Measured by Nuclear Magnetic Resonance Spectroscopy: The Framingham Study  

Microsoft Academic Search

Background: The sex differential in coronary heart disease (CHD) risk, which is not explained by male\\/ female differences in lipid and lipoprotein concentra- tions, narrows with age. We examined whether this differential CHD risk might, in part, be attributable to the sizes of lipoprotein particles or concentrations of lipoprotein subclasses. Methods: We analyzed frozen plasma samples from 1574 men and

David S. Freedman; James D. Otvos; Elias J. Jeyarajah; Irina Shalaurova; L. Adrienne Cupples; Helen Parise; Ralph B. D'Agostino; Peter W. F. Wilson; Ernst J. Schaefer

57

Effect of obesity on the plasma lipoprotein subclass profile in normoglycemic and normolipidemic men and women  

PubMed Central

Objective To determine the effect of obesity without the confounding effect of metabolic complications on the lipoprotein subclass profile in men and women. Design Cross-sectional study. Subjects 40 lean (BMI: 18.5–25 kg/m2) and 40 obese (BMI: 30–45 kg/m2) subjects, with blood pressure <140/90 mm Hg, fasting plasma glucose concentration <100 mg/dl and total triglyceride concentration <150 mg/dl; all obese subjects had normal oral glucose tolerance. Measurements Fasting concentrations of very low-, intermediate-, low-, and high-density lipoproteins (VLDL, IDL, LDL, and HDL, respectively) and average VLDL, LDL and HDL particle sizes were evaluated by using proton nuclear magnetic resonance spectroscopy. Results Obese compared with lean individuals of both sexes had increased plasma concentrations of VLDL (by ~50%), IDL (by ~100%), LDL (by ~50%), and to some extent HDL (by ~10%) particles (P<0.05). The contribution of large VLDL to total VLDL concentration, small LDL to total LDL concentration, and small HDL to total HDL concentration was greater in obese than lean subjects (P<0.05), resulting in larger average VLDL size but smaller average LDL and HDL sizes (P<0.05). Women, compared with men, had reduced concentrations of total VLDL particles (by ~10%) due to lower concentrations of large and medium VLDL, and a shift towards large at the expense of small HDL particles (P<0.05) with no difference in total HDL particle concentration. IDL and total LDL concentrations and LDL subclass distribution were not different between men and women. Conclusion Obesity is associated with pro-atherogenic alterations in the lipoprotein subclass profile, which may increase cardiovascular disease risk even in the absence of classical metabolic risk factors. On the other hand, the female cardiovascular disease risk advantage is probably largely related to differences in traditional lipid risk factors (plasma triglyceride and HDL-cholesterol concentrations) because sex differences in the plasma lipoprotein subclass profile are minimal.

Magkos, Faidon; Mohammed, B. Selma; Mittendorfer, Bettina

2008-01-01

58

Quantification of Lipoprotein Subclasses by Proton Nuclear Magnetic Resonance-Based Partial Least-Squares Regression Models  

Microsoft Academic Search

Background: Cardiovascular disease risk can be esti- mated in part on the basis of the plasma lipoprotein profile. Analysis of lipoprotein subclasses improves the risk evaluation, but the traditional methods are very time-consuming. Novel, rapid, and productive methods are therefore needed. Methods: We obtained plasma samples from 103 fasting people and determined the plasma lipoprotein subclass profiles by an established

Martin Petersen; Marianne Dyrby; Søren Toubro; Søren Balling Engelsen; Lars Nørgaard; Henrik Toft Pedersen; Jørn Dyerberg

59

Involvement of the Ca(2+)-dependent phosphorylation of a 20 kDa protein in the proliferative effect of high-density lipoproteins (subclass 3) on the adenocarcinoma cell line A549.  

PubMed Central

Previous studies from our laboratory demonstrated that high-density lipoproteins (subclass 3; HDL3) bind to sites specific for apolipoprotein AI on the human adenocarcinoma cell line A549 and that HDL3 binding promotes a mitogenic effect [Favre, Tazi, Le Gaillard, Bennis, Hachem and Soula (1993) J. Lipid Res. 34, 1093-1106]. In the present study, we have examined the cell proteins that showed modified phosphorylation after binding of HDL3 to specific sites, and the roles of Ca2+ and protein kinase C. Native HDL3 (but not tetranitromethane-modified HDL3) and Ca2+ ionophore A23187 strongly enhanced the phosphorylation of a 20 kDa protein (x 3.6) and, to a lower extent, the phosphorylation of 24 and 28 kDa proteins (x 2.2 and 2.6 respectively). The two effectors were equally able to stimulate cell growth. Down-regulation of protein kinase C by a 24 h incubation of cells with phorbol myristate acetate prevented the effects of HDL3 on the phosphorylation of 24 and 28 kDa proteins. However, the extent of phosphorylation of the 20 kDa protein was not affected. In contrast, activation of protein kinase C by a short incubation with phorbol myristate acetate resulted in inhibition of proliferation and an increase in 24 and 28 kDa (but not 20 kDa) protein phosphorylation. These results suggest that HDL3 putative receptors exert their proliferative effect on A549 cells through activation of a Ca(2+)-dependent protein kinase. This kinase activity is not modulated by phorbol ester and thus may be a calmodulin kinase or an isoenzyme of protein kinase C that is independent of phorbol ester. It allows a subsequent 20 kDa protein to be phosphorylated. Images Figure 1 Figure 2 Figure 3

Tazi, K A; Bonnafous, M; Favre, G; Soula, G; Le Gaillard, F

1995-01-01

60

Hypertriglyceridemia and unusual lipoprotein subclass distributions associated with late pregnancy  

SciTech Connect

In the human adult population elevated plasma triglyceride (TG) levels are associated with decreased high density lipoprotein-cholesterol (HDL-C) levels and decreased HDL and LDL particle sizes. Late pregnancy is a hypertriglyceridemic state where little is known about LDL and HDL subpopulation distribution. Plasma lipids, apolipoproteins (apo) and lipoprotein subpopulations were examined in 36 pregnant women at 36 wk pregnancy and 6 wk postpartum and correlated with HDL and LDL size. There was a significant decrease in LDL diameter at 36 wk pre, 25 {plus minus} 0.7 nm compared, with 6 wk post, 26.4 {plus minus} 0.8 nm. A total of 97% of the 36 wk pre subjects had small dense LDL which paralleled increases in apoB concentration. Unlike LDL HDL at 36 wks pre showed a significant increase in larger sized particles where HDL{sub 2b} predominated. There was a positive correlation between HDL{sub 2b} mass and apoAl and HDL-C concentrations. Late pregnancy is a metabolic state where the predominance of large, HDL{sub 2b} particles is discordant with the predominance of small LDL and elevated TG. This annual metabolic pattern may in part be due to hormonal changes occurring in late pregnancy.

Forte, T.M.; Kretchmer, N.; Silliman, K. (Lawrence Berkeley Lab., CA (United States))

1991-03-15

61

Lipoprotein subclasses in genetic studies: The Berkeley Data Set.  

National Technical Information Service (NTIS)

Data from the Berkeley Data Set was used to investigate familial correlations of HDL-subclasses. Analysis of the sibling intraclass correlation coefficient by HDL particle diameter showed that sibling HDL levels were significantly correlated for HDL(sub 2...

R. M. Krauss P. T. Williams P. J. Blanche A. Cavanaugh L. G. Holl

1992-01-01

62

Physical Activity versus Sedentary Behavior: Associations with Lipoprotein Particle Subclass Concentrations in Healthy Adults  

PubMed Central

Background Physical activity (PA) and sedentary behavior (SED) may have independent effects on health and disease. This might be due to PA and SED having distinct effects on lipoprotein metabolism. The aim of this study was to determine associations between lipoprotein subclass particle concentrations (-P) and accelerometer-measured SED and moderate-to-vigorous PA (MVPA) in a sample of healthy adult subjects. Methods Lipoprotein subclass particle concentrations were determined by proton nuclear magnetic resonance spectroscopy, whereas SED and MVPA were measured using Agtigraph GT1M and GT3X+ accelerometers. We obtained valid data in 73 subjects (30 men and 43 women, age 40.5 ± 10.6 years; body mass index 24.0 ± 2.8). Multiple regression analysis was used to determine associations (partial correlations) with lipoproteins. Results Positive associations were detected between SED and small VLDL-P, large LDL-P and TG (partial r = 0.24 to 0.25, p < .047). Corresponding associations were non-significant for MVPA (partial r = -0.12 to 0.04, p > .355). On the contrary, MVPA was positively associated with large HDL-P, average HDL size, Apo A1 and HDL-cholesterol (partial r = 0.28 to 0.50, p < .027), whereas SED was not (partial r = -0.06 to 0.07, p > .607). Conclusion There might be a specific effect of SED versus MVPA on lipoprotein metabolism. However, our results must be interpreted carefully due to possible effect-modification by gender and a low sample size. Thus, our findings should be viewed as preliminary.

Aadland, Eivind; Andersen, John Roger; Anderssen, Sigmund Alfred; Kvalheim, Olav Martin

2013-01-01

63

Relationships between serum lipid, lipoprotein, triglyceride-rich lipoprotein, and high-density lipoprotein particle concentrations in post-renal transplant patients*  

PubMed Central

Objective: Disturbances in lipid and lipoprotein profiles in patients after kidney transplantation (Tx) are still not understood. Methods: Serum levels of lipids, lipoprotein, triglyceride-rich lipoproteins (TRLs), and high-density lipoprotein (HDL) particles were determined, lipid and lipoprotein ratios were calculated, and their relationships in Tx patients with hypertriglyceridemia (HTG) and lower apolipoprotein AI (apoAI) concentration were examined. Serum lipid and lipoprotein levels were measured in 109 Tx patients and 89 healthy subjects. HDL particle levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Tx patients had disturbed concentration, composition, and metabolism of TRLs and HDL particles. Multivariance analysis showed significant and positive correlation between HDL cholesterol/apoAI (HDL-C/apoAI) and HDL-C/HDL ratios, which indicates that both ratios could sensitively reflect changes in the HDL subclasses and their distribution into smaller size particles. In Tx patients, the decreased HDL-C/apoAI ratio indicates that, along with the decreased apoAI concentration, the HDL-C level is decreased. However, a low HDL-C/HDL ratio indicates that HDL particles in Tx patients transport lesser content of HDL-C but more triglyceride (TG) (high TG/HDL ratio), and thus are hypercatabolized and removed; therefore, concentration of HDL particles in serum was decreased. Conclusion: The decrease of HDL-C/apoAI ratio seems to be a good marker of HDL subclass distribution into smaller size particles.

Kimak, Elzbieta; Halabis, Magdalena; Baranowicz-Gaszczyk, Iwona

2010-01-01

64

Hypertriglyceridemia during late pregnancy is associated with the formation of small dense low-density lipoproteins and the presence of large buoyant high-density lipoproteins.  

PubMed

Late pregnancy is a unique metabolic state where there are transient increases in the concentrations of plasma triglyceride (TG), cholesterol, and apolipoprotein (apo) B. Despite the hypertriglyceridemic environment, we recently reported that there is an unusual shift in high-density lipoprotein (HDL) subclass distribution from smaller HDL subclasses to the largest, most buoyant HDL2b subclass. In the present investigation, we determined whether the subclasses of low-density lipoprotein (LDL) also change during this transient hyperlipidemic state and whether such changes were associated with plasma TG and apolipoprotein concentrations. Thirty-six Hispanic subjects at 35 to 36 weeks' gestation and at 6 weeks' postpartum were studied. At 35 to 36 weeks of gestation, plasma concentrations of TG, cholesterol, and apo B were increased (218 +/- 62, 234 +/- 48, and 130 +/- 35 mg/dL, respectively) over levels at 6 weeks' postpartum (112 +/- 69, 197 +/- 36, and 97 +/- 25 mg/dL respectively). However, lipoprotein(a) [Lp(a)] concentrations were not changed during pregnancy compared with postpartum. LDL subclass patterns (A, B, or I) were determined by nondenaturing polyacrylamide gradient gel electrophoresis in our group of 36 pregnant women. During late pregnancy, 97% of subjects were categorized as LDL subclass patterns B or I, indicating that small, dense LDL particles predominated. This predominance of small, dense LDL was associated with plasma TG concentration, where there was a significant inverse relationship (r = -.45, P < .01) between the LDL peak particle diameter and plasma TG concentration. In an apparent anomaly, there were significant increases in the concentrations of HDL cholesterol (HDL-C) and HDL2 mass, even though small, dense LDL particles predominated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8052144

Silliman, K; Shore, V; Forte, T M

1994-08-01

65

Sulfated Polyvinylalcohol Based Low Density Lipoprotein Binders.  

National Technical Information Service (NTIS)

The thesis covers the synthesis and characterization of three Low Density Lipoprotein (LDL) binders based on sulfated polyvinylalcohol. These binders are to be used in extracorporeal bloodtreatment in order to reduce high plasma LDL levels, as encountered...

N. Maaskant

1986-01-01

66

Functional Assay of High-Density Lipoprotein.  

National Technical Information Service (NTIS)

This invention provides novel assays that are prognostic and/or diagnostic for atherosclerosis or risk of atherosclerosis. It was discovered that high density lipoprotein (HDL) or components thereof can prevent the oxidation of lipids (e.g., lipids presen...

A. M. Fogelman M. Navab S. Hama

2005-01-01

67

Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance.  

PubMed

The insulin resistance syndrome (IRS) is associated with dyslipidemia and increased cardiovascular disease risk. A novel method for detailed analyses of lipoprotein subclass sizes and particle concentrations that uses nuclear magnetic resonance (NMR) of whole sera has become available. To define the effects of insulin resistance, we measured dyslipidemia using both NMR lipoprotein subclass analysis and conventional lipid panel, and insulin sensitivity as the maximal glucose disposal rate (GDR) during hyperinsulinemic clamps in 56 insulin sensitive (IS; mean +/- SD: GDR 15.8 +/- 2.0 mg. kg(-1). min(-1), fasting blood glucose [FBG] 4.7 +/- 0.3 mmol/l, BMI 26 +/- 5), 46 insulin resistant (IR; GDR 10.2 +/- 1.9, FBG 4.9 +/- 0.5, BMI 29 +/- 5), and 46 untreated subjects with type 2 diabetes (GDR 7.4 +/- 2.8, FBG 10.8 +/- 3.7, BMI 30 +/- 5). In the group as a whole, regression analyses with GDR showed that progressive insulin resistance was associated with an increase in VLDL size (r = -0.40) and an increase in large VLDL particle concentrations (r = -0.42), a decrease in LDL size (r = 0.42) as a result of a marked increase in small LDL particles (r = -0.34) and reduced large LDL (r = 0.34), an overall increase in the number of LDL particles (r = -0.44), and a decrease in HDL size (r = 0.41) as a result of depletion of large HDL particles (r = 0.38) and a modest increase in small HDL (r = -0.21; all P < 0.01). These correlations were also evident when only normoglycemic individuals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race. Discontinuous analyses were also performed. When compared with IS, the IR and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL), which produced an increase in serum triglycerides; a decrease in LDL size as a result of an increase in small and a reduction in large LDL subclasses, plus an increase in overall LDL particle concentration, which together led to no difference (IS versus IR) or a minimal difference (IS versus diabetes) in LDL cholesterol; and a decrease in large cardioprotective HDL combined with an increase in the small HDL subclass such that there was no net significant difference in HDL cholesterol. We conclude that 1) insulin resistance had profound effects on lipoprotein size and subclass particle concentrations for VLDL, LDL, and HDL when measured by NMR; 2) in type 2 diabetes, the lipoprotein subclass alterations are moderately exacerbated but can be attributed primarily to the underlying insulin resistance; and 3) these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel. It will be important to study whether NMR lipoprotein subclass parameters can be used to manage risk more effectively and prevent cardiovascular disease in patients with the IRS. PMID:12540621

Garvey, W Timothy; Kwon, Soonho; Zheng, Deyi; Shaughnessy, Sara; Wallace, Penny; Hutto, Amy; Pugh, Kimberly; Jenkins, Alicia J; Klein, Richard L; Liao, Youlian

2003-02-01

68

Alterations of HDL subclasses in hyperlipidemia  

Microsoft Academic Search

Background: It is generally accepted that different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL is known to directly influence the atherogenic process and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Method: The relative apolipoprotein (apo)A-I contents (% apoA-I) of plasma HDL subclasses were determined by two-dimensional gel electrophoresis

Yanhua Xu; Mingde Fu

2003-01-01

69

Abnormal high density lipoproteins in cerebrotendinous xanthomatosis  

Microsoft Academic Search

The plasma lipoprotein profiles and high density lipoproteins (HDL) were characterized in patients with the genetic disease cerebrotendinous xanthomatosis (CTX). The mean HDL-cholesterol concentration in the CTX plasmas was 14.5 +\\/- 3.2 mg\\/dl, about one-third the normal value. The low HDL-cholesterol reflects a low concentration and an abnormal lipid composition of the plasma HDL. Relative to normal HDL, the cholesteryl

V. Shore; G. Salen; F. W. Cheng; T. Forte; S. Shefer; G. S. Tint; F T Lindgren

1981-01-01

70

Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet  

PubMed Central

Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles. We sought to determine whether increases in plasma Lp(a) induced by a low-fat high-carbohydrate (LFHC) diet are related to changes in OxPL and LDL subclasses. We studied 63 healthy subjects after 4 weeks of consuming, in random order, a high-fat low-carbohydrate (HFLC) diet and a LFHC diet. Plasma concentrations of Lp(a) (P < 0.01), OxPL/apolipoprotein (apo)B (P < 0.005), and OxPL-apo(a) (P < 0.05) were significantly higher on the LFHC diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller (P < 0.0001). Diet-induced changes in Lp(a) were strongly correlated with changes in OxPL/apoB (P < 0.0001). The increases in plasma Lp(a) levels after the LFHC diet were also correlated with decreases in medium LDL particles (P < 0.01) and increases in very small LDL particles (P < 0.05). These results demonstrate that induction of increased levels of Lp(a) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.

Faghihnia, Nastaran; Tsimikas, Sotirios; Miller, Elizabeth R.; Witztum, Joseph L.; Krauss, Ronald M.

2010-01-01

71

Atherosclerosis regression: Is low-density lipoprotein or high-density lipoprotein the answer?  

Microsoft Academic Search

Lowering low-density lipoprotein cholesterol is the cornerstone of risk modification in patients with established coronary\\u000a artery disease. Considerable attention is currently focused on developing pharmacologic agents that promote the biologic activity\\u000a of high-density lipoprotein. Advances in imaging of the artery wall provide the opportunity to evaluate the impact of medical\\u000a therapies on serial changes in plaque burden. A number of

Stephen J. Nicholls; E. Murat Tuzcu; Steven E. Nissen

2007-01-01

72

Familial apolipoprotein AI and apolipoprotein CIII deficiency. Subclass distribution, composition, and morphology of lipoproteins in a disorder associated with premature atherosclerosis.  

PubMed Central

Lipoprotein classes isolated from the plasma of two patients with apolipoprotein AI (apo AI) and apolipoprotein CIII (apo CIII) deficiency were characterized and compared with those of healthy, age- and sex-matched controls. The plasma triglyceride values for patients 1 and 2 were 31 and 51 mg/dl, respectively, and their cholesterol values were 130 and 122 mg/dl, respectively; the patients, however, had no measurable high density lipoprotein (HDL)-cholesterol. Analytic ultracentrifugation showed that patients' S degrees f 0-20 lipoproteins possess a single peak with S degrees f rates of 7.4 and 7.6 for patients 1 and 2, respectively, which is similar to that of the controls. The concentration of low density lipoprotein (LDL) (S degrees f 0-12) particles, although within normal range (331 and 343 mg/dl for patients 1 and 2, respectively), was 35% greater than that of controls. Intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) (S degrees f 20-400) were extremely low in the patients. HDL in the patients had a calculated mass of 15.4 and 11.8 mg/dl for patients 1 and 2, respectively. No HDL could be detected by analytic ultracentrifugation, but polyacrylamide gradient gel electrophoresis (gge) revealed that patients possessed two major HDL subclasses: (HDL2b)gge at 11.0 nm and (HDL3b)gge at 7.8 nm. The major peak in the controls, (HDL3a)gge, was lacking in the patients. Gradient gel analysis of LDL indicated that patients' LDL possessed two peaks: a major one at 27 nm and a minor one at 26 nm. The electron microscopic structure of patients' lipoprotein fractions was indistinguishable from controls. Patients' HDL were spherical and contained a cholesteryl ester core, which suggests that lecithin/cholesterol acyltransferase was functional in the absence of apo AI. The effects of postprandial lipemia (100-g fat meal) were studied in patient 1. The major changes were the appearance of a 33-nm particle in the LDL density region of 1.036-1.041 g/ml and the presence of discoidal particles (12% of total particles) in the HDL region. The latter suggests that transformation of discs to spheres may be delayed in the patient. The simultaneous deficiency of apo AI and apo CIII suggests a dual defect in lipoprotein metabolism: one in triglyceride-rich lipoproteins and the other in HDL. The absence of apo CIII may result in accelerated catabolism of triglyceride-rich particles and an increased rate of LDL formation. Additionally, absence of apo CIII would favor rapid uptake of apo E-containing remnants by liver and peripheral cells. Excess cellular cholesterol would not be removed by the reverse cholesterol transport mechanism since HDL levels are exceedingly low and thus premature atherosclerosis occurs. Images

Forte, T M; Nichols, A V; Krauss, R M; Norum, R A

1984-01-01

73

Statins and metabolism of high density lipoprotein.  

PubMed

Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis. Statins are widely and successfully used for lowering plasma cholesterol levels causing up to 45% reduction of plasma cholesterol and considerable reduction in risk of cardiovascular diseases. The main atheroprotective action of statins is reduction of plasma low density lipoprotein levels due to improved clearance of this lipoprotein by the liver. In addition, statins cause mild elevation of high density lipoprotein (HDL) concentration, but the mechanism responsible for this effect of statins on HDL metabolism is not well understood. It has been hypothesized that statins affect the HDL level through inhibition of cholesteryl ester transfer protein activity or by stimulating apolipoprotein A-I synthesis. Increased cholesterol efflux from liver due to raised expression of the ABCA1 transporter may also elevate HDL levels. Whereas raising the plasma HDL-C concentration may contribute to the atheroprotective effect of statins, its magnitude is uncertain and additional mechanisms that improve the functionality of HDL may be equally or more important. In this review we analyze what is currently known about effect of statins on HDL metabolism and on reverse cholesterol transport in particular. PMID:17630948

Sviridov, Dmitri; Nestel, Paul; Watts, Gerald

2007-07-01

74

High density lipoproteins and atherosclerosis: emerging aspects  

PubMed Central

High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes. Furthermore, during inflammation, the composition of this class of lipoproteins varies to a large extent, thus promoting the formation of dysfunctional HDL. The aim of this review is to discuss the emerging role of HDL in modulating the activity of immune cells and immune-inflammatory mediators during atherogenesis.

Sala, Federica; Catapano, Alberico Luigi; Norata, Giuseppe Danilo

2012-01-01

75

Opportunities for Using Lipoprotein Subclass Profile by Nuclear Magnetic Resonance Spectroscopy in Assessing Insulin Resistance and Diabetes Prediction  

PubMed Central

Abstract The incidence of type 2 diabetes mellitus (T2DM) has reached epidemic levels, and current trends indicate that its prevalence will continue to rise. The development of T2DM can be delayed by several years, and may even be prevented, by identifying individuals at risk for T2DM and treating them with lifestyle modification and/or pharmacological therapies. There are a number of methods available for assessing the insulin resistance (IR) that characterizes, and is the precursor to, T2DM. However, current clinical methods for assessing IR, based on measures of plasma glucose and/or insulin are either laborious and time-consuming or show a low specificity. IR manifests its earliest measurable abnormalities through changes in lipoproteins, and thus we propose that by examining lipoprotein subclass profile, it may be possible to alert physicians and patients to a heightened risk of developing diabetes. This will allow us to institute appropriate lifestyle changes and treatment potentially to delay the onset or possibly prevent the progression to diabetes.

Garvey, W. Timothy; Dall, Tara; Honigberg, Robert; Pourfarzib, Ray

2012-01-01

76

Leptospirosis is Associated with Markedly Increased Triglycerides and Small Dense Low-Density Lipoprotein and Decreased High-Density Lipoprotein  

Microsoft Academic Search

The objective of the present study was to evaluate the effects of acute infection with Leptospira interrogans on lipids, lipoproteins and associated enzymes. Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol\\u000a (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins (apo) A-?, B, E, C-II, C-III and\\u000a lipoprotein (a) [Lp(a)] were determined in patients with Leptospirosis on diagnosis and

Irene F. Gazi; Fotini A. Apostolou; Evangelos N. Liberopoulos; Theodosios D. Filippatos; Constantinos C. Tellis; Moses S. Elisaf; Alexandros D. Tselepis

77

Alcohol alters low density lipoprotein composition and metabolism  

SciTech Connect

Two separate studies were conducted to examine the effect of ethanol (EtOH) dose on atherogenic low density lipoprotein (LDL) subfractions and LDL metabolism in vivo. In the first study, male, atherosclerosis-susceptible squirrel monkeys were divided in three treatments: controls fed liquid diet, and low and high alcohol groups given liquid diet with vodka substituted for carbohydrate at 12% and 24% of calories, respectively. After 6 months, LDL subclasses (LDL{sub 1a}, LDL{sub 1b} and LDL{sub 2}) were isolated by density gradient ultracentrifugation and polyacrylamide gradient gel electrophoresis, and their lipid and protein composition was determined. Low dose EtOH had no effect on LDL subfraction distribution while 24% EtOH resulted in an increase in the larger (LDL{sub 1a} and LDL{sub 1b}), buoyant subspecies without affecting the level of the more atherogenic, smaller, denser LDL{sub 2} particles. In the second study, {sup 125}I-LDL apolipoprotein B (apo B) was injected intravenously into Control and High EtOH monkeys and kinetic analyses were performed. Although the absolute catabolic rate (LDL production) was not altered, High EtOH primates showed a reduction in the fractional catabolic rate and a longer LDL apoB residence time.

Hoinacki, J.; Brown, J.; Dawson, M.; Deschenes, R.; Mulligan, J. (Univ. of Lowell, MA (United States))

1991-03-11

78

Abnormal high density lipoproteins in cerebrotendinous xanthomatosis  

SciTech Connect

The plasma lipoprotein profiles and high density lipoproteins (HDL) were characterized in patients with the genetic disease cerebrotendinous xanthomatosis (CTX). The mean HDL-cholesterol concentration in the CTX plasmas was 14.5 +/- 3.2 mg/dl, about one-third the normal value. The low HDL-cholesterol reflects a low concentration and an abnormal lipid composition of the plasma HDL. Relative to normal HDL, the cholesteryl esters are low, free cholesterol and phospholipids essentially normal, and triglycerides increased. The ratio of apoprotein (apo) to total cholesterol in the HDL of CTX was two to three times greater than normal. In the CTX HDL, the ratio of apoAI to apoAII was high, the proportion of apoC low, and a normally minor form of apoAI increased relative to other forms. The HDL in electron micrographs appeared normal morphologically and in particle size. The adnormalities in lipoprotein distribution profiles and composition of the plasma HDL result from metabolic defects that are not understood but may be linked to the genetic defect in bile acid synthesis in CTX. As a consequence, it is probable that the normal functions of the HDL, possibly including modulation of LDL-cholesterol uptake and the removal of excess cholesterol from peripheral tissues, are perturbed significantly in this disease.

Shore, V. (Lawrence Livermore Lab., CA); Salen, G.; Cheng, F.W.; Forte, T.; Shefer, S.; Tint, G.S.

1981-11-01

79

High Density Lipoprotein and it's Dysfunction  

PubMed Central

Plasma high-density lipoprotein cholesterol(HDL-C) levels do not predict functionality and composition of high-density lipoprotein(HDL). Traditionally, keeping levels of low-density lipoprotein cholesterol(LDL-C) down and HDL-C up have been the goal of patients to prevent atherosclerosis that can lead to coronary vascular disease(CVD). People think about the HDL present in their cholesterol test, but not about its functional capability. Up to 65% of cardiovascular death cannot be prevented by putative LDL-C lowering agents. It well explains the strong interest in HDL increasing strategies. However, recent studies have questioned the good in using drugs to increase level of HDL. While raising HDL is a theoretically attractive target, the optimal approach remains uncertain. The attention has turned to the quality, rather than the quantity, of HDL-C. An alternative to elevations in HDL involves strategies to enhance HDL functionality. The situation poses an opportunity for clinical chemists to take the lead in the development and validation of such biomarkers. The best known function of HDL is the capacity to promote cellular cholesterol efflux from peripheral cells and deliver cholesterol to the liver for excretion, thereby playing a key role in reverse cholesterol transport (RCT). The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High antioxidant and anti-inflammatory activities of HDL are associated with protection from CVD. This review addresses the current state of knowledge regarding assays of HDL functions and their relationship to CVD. HDL as a therapeutic target is the new frontier with huge potential for positive public health implications.

Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

2012-01-01

80

Regulation of high density lipoprotein levels  

SciTech Connect

An increasing awareness of the physiologic and pathologic importance of serum high density lipoproteins (HDL) has led to a large number of observations regarding factors which influence their concentrations. HDL consists of a heterogeneous collection of macromolecules with diverse physical properties and chemical constituents. While laboratory techniques have made it possible to measure HDL and their individual components, there are as yet large gaps in our knowledge of the biochemical mechanisms and clinical significance of changes in these laboratory parameters. In this review, current concepts of the structure and metabolism of HDL will be briefly summarized, and the factors influencing their levels in humans will be surveyed. 313 references.

Krauss, R.M.

1982-03-01

81

Templated Spherical High Density Lipoprotein Nanoparticles  

PubMed Central

We report the synthesis of high density lipoprotein (HDL) bio-mimetic nanoparticles capable of binding cholesterol. These structures use a gold nanoparticle core to template the assembly of a mixed phospholipid layer and the adsorption of apolipoprotein A-I. These synthesized structures have the general size and surface composition of natural HDL, and importantly, bind free cholesterol (Kd = 4 nM). The determination of the Kd for these particles, with respect to cholesterol complexation, provides a key starting and comparison point for measuring and evaluating the properties of subsequently developed synthetic versions of HDL.

Thaxton, C. Shad; Daniel, Weston L.; Giljohann, David A.; Thomas, Audrey D.; Mirkin, Chad A.

2010-01-01

82

Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia  

Microsoft Academic Search

This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia. This was a multicenter, randomized, open-label, parallel-design study of patients with total cholesterol >200 mg\\/dl, triglycerides between 200 and 800 mg\\/dl, and apolipoprotein B >110 mg\\/dl. Patients were randomly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg

James M McKenney; Lisa S McCormick; Ernst J Schaefer; Donald M Black; Michael L Watkins

2001-01-01

83

Management of non-high-density lipoprotein abnormalities  

Microsoft Academic Search

Epidemiological evidence supports the use of non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B-100 (apoB), and low-density lipoprotein particles as markers of atherogenic risk. Treatment guidelines also identify these as additional targets of lipid-modifying intervention in patients with elevated triglycerides (TG). Even when TG are only moderately elevated, many patients on statin monotherapy who have achieved targets for low-density lipoprotein cholesterol (LDL-C)

Robert S. Rosenson

2009-01-01

84

Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children  

Microsoft Academic Search

Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help pre- vent coronary artery disease (CAD), it may be useful to under- stand risk factors during childhood and adolescence. In the present study, we evaluated low density

Takao Ohta; Yoshiko Kakiuti; Kazuko Kurahara; Keijiro Saku; Ichiro Matsuda

85

Effect of Early Enteral Feeding on Apolipoprotein AI Levels and High-Density Lipoprotein Heterogeneity in Preterm Infants  

Microsoft Academic Search

Background\\/Aim: We have previously shown that infants receiving total parenteral nutrition have low apolipoprotein AI levels which are associated with high-density lipoprotein (HDL) class distributions as in lecithin:cholesterol acyltransferase deficiency. This study investigates the influence of early enteral feedings on apolipoprotein AI and HDL subclasses. Methods: Apolipoprotein AI and HDL distributions were determined in 15 total parenterally fed preterm infants

Orsolya Genzel-Boroviczény; Yvonne Göbel; Berthold Koletzko

2002-01-01

86

Controversy on high density lipoprotein raising therapy.  

PubMed

Decreased high density lipoproteins (HDL) plasma levels are a recognized independent risk factor for atherosclerotic cardiovascular disease. Attempts were therefore initiated to pharmacologically raise plasma HDL cholesterol, and the most impressive increase was obtained by inhibiting cholesteryl ester transfer protein (CETP) by means of the synthetic compound torcetrapib. Clinical trials were however disappointing, as torcetrapib increased mortality and did not reduce the progression of atherosclerosis. According to some view, it was claimed that CETP inhibition is unfavourable and that development of this class of compounds should be abandoned. Controversy nevertheless stimulated research on HDL structure, heterogeneity and functions which are not limited to reverse cholesterol transport and exert antioxidant and antiinflammatory actions. It could also be demonstrated that the deleterious effects of torcetrapib are compound specific, including its tight binding to CETP on HDL particles, thereby blocking both neutral lipids and phospholipid transfer from HDL to other lipoproteins, and would also exert an off-target effect by increasing plasma sodium and decreasing potasium concentrations (an aldosterone-like effect). As the structure of CETP was elucidated, it became possible to design CETP inhibitors that lack such off-target toxicity and may successfully slow the progression of atherosclerosis. Noteworthy, mice and rats naturally lacking CETP are resistant to diet induced atherosclerosis, while rabbits with high CETP levels are very susceptible. Families with deficient activity and exceptional longevity had also been reported. PMID:21428174

Cucuianu, M; Bruda?c?, Ioana

2010-01-01

87

Ethnic differences in lipoprotein subclasses in obese adolescents: importance of liver and intraabdominal fat accretion1234  

PubMed Central

Background: Recently, the deleterious metabolic effects of visceral fat [visceral adipose tissue (VAT)] deposition were challenged, and liver fat emerged as having a key independent role in the modulation of cardiometabolic risk factors. Objective: We explored the relation between liver fat content and VAT in 3 ethnic groups and evaluated whether the ethnic differences in the distributions of lipoprotein concentrations and sizes were associated with the hepatic fat fraction (HFF), VAT, or both. Design: In a multiethnic group of 33 white, 33 African American, and 33 Hispanic obese adolescents with normal glucose tolerance, we measured VAT and HFF by using magnetic resonance imaging. Fasting lipoprotein particle number and size were measured by using nuclear magnetic resonance spectroscopy. To assess the association between VAT and HFF, we categorized VAT into tertiles. Results: In each ethnic group, HFF values increased between successive tertiles of VAT. After multivariate adjustment and in comparison with the 2 other groups, African Americans showed lower triglyceride (P = 0.001) and higher HDL (P = 0.03) concentrations, lower concentrations of total (P = 0.007), large (P = 0.005), and medium (P lt 0.0001) VLDL, but higher concentrations of large HDL particles (P = 0.01) and larger HDL (P = 0.005). In multivariate linear models, independent of ethnicity, VAT was a significant predictor for large HDL (P = 0.003) and total small LDL (P = 0.001) concentrations, whereas HFF significantly predicted large VLDL (P = 0.03) concentrations. Conclusion: Liver fat accretion, independent of VAT, may play a role in the ethnic differences seen in large VLDL particles. This trial was registered at clinicaltrials.gov as NCT00536250.

D'Adamo, Ebe; Northrup, Veronika; Weiss, Ram; Santoro, Nicola; Pierpont, Bridget; Savoye, Mary; O'Malley, Grace

2010-01-01

88

A molecular model of high density lipoproteins.  

PubMed

Based on the analysis of recombined lipidapoprotein complexes by C-13 and P-31 nuclear magnetic resonance spectroscopy and circular dichroism [Assmann, G., Sokoloski, E. A. & Brewer, H. B., Jr. (1974) Proc. Nat. Acad. Sci. USA 71, 549-553; Assmann, G., Highet, R. J., Sokoloski, E. A. & Brewer, H. B., Jr. (1974) Proc. Nat. Acad. Sci. USA 71, in press; Assmann, G. & Brewer, H. B., Jr. (1974) Proc. Nat. Acad. Sci. USA 71, 989-993] and the identification of conformational amphipathic regions in apoproteins, a new model for human high density lipoproteins is proposed. This model is analogous to membrane models proposed by Singer, in that protein "icebergs" are embedded in a "sea" of lipid. PMID:4364543

Assmann, G; Brewer, H B

1974-04-01

89

Nanotechnology for Synthetic High Density Lipoproteins  

PubMed Central

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

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

2014-01-01

90

Computational Lipidology: Predicting Lipoprotein Density Profiles in Human Blood Plasma  

PubMed Central

Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond “bad” and “good” cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL), we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile) is calculated. As our main results, we (i) successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii) assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS), revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii) present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia.

Hubner, Katrin; Schwager, Thomas; Winkler, Karl; Reich, Jens-Georg; Holzhutter, Hermann-Georg

2008-01-01

91

Low Density Lipoprotein and High Density LipoproteinMediated Signal Transduction and Exocytosis in Alveolar Type II Cells  

Microsoft Academic Search

Low density lipoproteins (LDL) and high density lipoproteins (HDL) from serum stimulate signal-transduction pathways and exocytosis in rat alveolar type II cells. Both LDL and HDL stimulated primary cultures of type II cells to secrete phosphatidylcholine (PtdCho), the major phospholipid component of pulmonary surfactant. The effects on secretion were preceded temporally by stimulation of inositol phospholipid catabolism, calcium mobilization, and

Tatyana A. Voyno-Yasenetskaya; Leland G. Dobbs; Sandra K. Erickson; Robert L. Hamilton

1993-01-01

92

Intermediate-density lipoproteins, diabetes and coronary artery disease  

Microsoft Academic Search

The results of various studies suggest that hypertriglyceridaemia is associated with an increased risk of coronary artery disease. It is unclear, however, which particular triglyceride (TG)-rich lipoproteins contribute to the risk. Different types of TG-rich lipoprotein differ in function, composition, size and density. TG-rich lipoproteins in the range Svedberg flotation (Sf) 12–60 have been shown to be associated with angiographic

George Steiner

1998-01-01

93

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

PubMed Central

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

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

2011-01-01

94

Human low-density lipoprotein receptor gene and its regulation  

Microsoft Academic Search

The low-density lipoprotein (LDL) receptor is a transmembrane glycoprotein that mediates the binding and endocytosis of lipoproteins containing apolipoprotein B and E, especially the cholesterol-rich LDL. Mutations in the LDL receptor gene can produce dysfunctional LDL receptors and cause familial hypercholesterolemia. The expression of the LDL receptor gene is under an intriguing regulation by sterol and nonsterol mediators either at

Wei-Jia Kong; Jingwen Liu; Jian-Dong Jiang

2006-01-01

95

Activation of lipoprotein lipase increases serum high density lipoprotein 2 cholesterol and enlarges high density lipoprotein 2 particles in rats.  

PubMed

It is known that postheparin plasma lipoprotein lipase (LPL) activity correlates with serum high density lipoprotein cholesterol (HDL-C) levels in humans and animals. Furthermore, LPL has been reported to cause enlargement of HDL particle size in vitro. However, these effects have not yet been experimentally proven. The aim of this study was to determine whether LPL has a role in increase in HDL-C and enlargement of HDL particle by activating the LPL function with NO-1886, the LPL promoting agent. NO-1886 administration increased postheparin plasma LPL activity without influencing hepatic triglyceride lipase activity. NO-1886 increased serum HDL(2)-cholesterol (HDL(2)-C) concentration and enlarged HDL(2) particle size, but did not increase serum HDL(3)-cholesterol concentration or enlarge HDL(3) particle size. Also, serum HDL(2)-C concentrations were positively correlated with HDL(2) particle size (r=0.910). Our study demonstrates that the LPL activation induced with NO-1886 may cause production of HDL(2)-C by catabolism of triglyceride-rich lipoproteins and enlarges HDL(2) particle size in rats. PMID:21756896

Kusunoki, Masataka; Tsutsumi, Kazuhiko; Sato, Daisuke; Nakamura, Aki; Habu, Satoshi; Mori, Yuichi; Morishita, Munehiko; Yonemoto, Takayuki; Miyata, Tetsuro; Nakaya, Yutaka; Nakamura, Takao

2011-10-01

96

Nanobiotechnology applications of reconstituted high density lipoprotein  

PubMed Central

High-density lipoprotein (HDL) plays a fundamental role in the Reverse Cholesterol Transport pathway. Prior to maturation, nascent HDL exist as disk-shaped phospholipid bilayers whose perimeter is stabilized by amphipathic apolipoproteins. Methods have been developed to generate reconstituted (rHDL) in vitro and these particles have been used in a variety of novel ways. To differentiate between physiological HDL particles and non-natural rHDL that have been engineered to possess additional components/functions, the term nanodisk (ND) is used. In this review, various applications of ND technology are described, such as their use as miniature membranes for solubilization and characterization of integral membrane proteins in a native like conformation. In other work, ND harboring hydrophobic biomolecules/drugs have been generated and used as transport/delivery vehicles. In vitro and in vivo studies show that drug loaded ND are stable and possess potent biological activity. A third application of ND is their use as a platform for incorporation of amphiphilic chelators of contrast agents, such as gadolinium, used in magnetic resonance imaging. Thus, it is demonstrated that the basic building block of plasma HDL can be repurposed for alternate functions.

2010-01-01

97

High density lipoprotein and cardiovascular diseases.  

PubMed

Several epidemiological studies have clearly shown that low plasma levels of high density lipoprotein cholesterol (HDL-C) represent a cardiovascular disease (CVD) risk factor. However, it is unclear if there is a causal association between HDL-C concentration and CVD. A recent study published in the Lancet, which performed two Mendelian randomization analyses, showed that increased HDL-C levels were not associated with a decreased risk of myocardial infarction. These findings, together with the termination of the niacin-based AIM-HIGH trial and the discontinuation of cholesteryl ester transfer protein inhibitor dalcetrapib, challenge the concept that raising of plasma HDL-C will uniformly translate into reductions in CVD risk. HDL particles exhibit several anti-atherosclerotic properties, such as anti-inflammatory and anti-oxidative activities and cellular cholesterol efflux activity. Furthermore, HDL particles are very heterogeneous in terms of size, structure, composition and metabolism. HDL functionality may be associated more strongly with CVD risk than the traditional HDL-C levels. More research is needed to assess the association of the structure of HDL particle with its functionality and metabolism. PMID:23888190

Filippatos, Theodosios D; Elisaf, Moses S

2013-07-26

98

High-density lipoprotein cholesterol: How High  

PubMed Central

The high-density lipoprotein cholesterol (HDL-C) is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD) risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP) is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

Rajagopal, G.; Suresh, V.; Sachan, Alok

2012-01-01

99

Association of Cholesteryl Ester Transfer Protein-TaqIB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease Risk The Framingham Study  

Microsoft Academic Search

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron

Jose M. Ordovas; L. Adrienne Cupples; Dolores Corella; James D. Otvos; Doreen Osgood; Antonia Martinez; Carlos Lahoz; Oscar Coltell; Peter W. F. Wilson; Ernst J. Schaefer

100

Alterations in plasma lipids, lipoproteins and high density lipoprotein subfractions in peripheral arterial disease  

Microsoft Academic Search

The concentrations of the major lipoprotein classes and of high density lipoprotein (HDL) subfractions in 63 male patients with arteriosclerosis of the lower limbs (claudication) were determined and compared with values from 63 healthy controls. The patients with peripheral arterial disease (PAD) had reduced levels of total HDL-cholesterol and HDL2b of large particle size, increased levels of small HDL3C particles

Beverley F Mowat; E. Roy Skinner; Heather M Wilson; Gillian C Leng; F. Gerald R Fowkes; David Horrobin

1997-01-01

101

Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia  

Microsoft Academic Search

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very—low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (?48.7%, P < .01)

Youssef Saïdi; Didier Sich; Anne Camproux; Monique Egloff; Marie-Christine Federspiel; Valérie Gautier; Alain Raisonnier; Gérard Turpin; Isabel Beucler

1999-01-01

102

Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets  

PubMed Central

Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface. Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence of interfacial tension becomes significant for particles with a radius of ?5 nm, when the area per molecule in the surface region is <1.4 nm2. Further, interfacial tensions in the used HDL and LDL models are essentially unaffected by single apo-proteins at the surface. Finally, interfacial tensions of lipoproteins are higher than in thermodynamically stable droplets, suggesting that HDL and LDL are kinetically trapped into a metastable state.

Ollila, O. H. Samuli; Lamberg, Antti; Lehtivaara, Maria; Koivuniemi, Artturi; Vattulainen, Ilpo

2012-01-01

103

High Density Lipoprotein Metabolism in Man  

PubMed Central

The turnover of 125I-high density lipoprotein (HDL) was examined in a total of 14 studies in eight normal volunteers in an attempt to determine the metabolic relationship between apolipoproteins A-I (apoA-I) and A-II (apoA-II) of HDL and to define further some of the determinants of HDL metabolism. All subjects were first studied under conditions of an isocaloric balanced diet (40% fat, 40% carbohydrate). Four were then studied with an 80% carbohydrate diet, and two were studied while receiving nicotinic acid (1 g three times daily) and ingesting the same isocaloric balanced diet. The decay of autologous 125I-HDL and the appearance of urinary radioactivity were followed for at least 2 wk in each study. ApoA-I and apoA-II were isolated by Sephadex G-200 chromatography from serial plasma samples in each study. The specific activities of these peptides were then measured directly. It was found that the decay of specific activity of apoA-I and apoA-II were parallel to one another in all studies. The mean half-life of the terminal portion of decay was 5.8 days during the studies with a balanced diet. Mathematical modeling of the decay of plasma radioactivity and appearance of urinary radioactivity was most consistent with a two-compartment model. One compartment is within the plasma and exchanges with a nonplasma component. Catabolism occurs from both of these compartments. With a balanced isocaloric diet, the mean synthetic rate for HDL protein was 8.51 mg/kg per day. HDL synthesis was not altered by the high carbohydrate diet and was only slightly decreased by nicotinic acid treatment. These perturbations had effects on HDL catabolic pathways that were reciprocal in many respects. With an 80% carbohydrate diet, the rate of catabolism from the plasma compartment rose by a mean of 39.1%; with nicotinic acid treatment, it fell by 42.2%. Changes in the rate of catabolism from the second compartment were generally opposite those in the rate of catabolism from the plasma compartment, suggesting that these two catabolic pathways may be reciprocally regulated. Images

Blum, Conrad B.; Levy, Robert I.; Eisenberg, Shlomo; Hall, Marshall; Goebel, Robert H.; Berman, Mones

1977-01-01

104

Hyperinsulinemia and insulin resistance are associated with multiple abnormalities of lipoprotein subclasses in glucose-tolerant relatives of NIDDM patients. Botnia Study Group.  

PubMed

We studied the subclasses of plasma lipoproteins in normolipidemic, glucose-tolerant male relatives of noninsulin dependent diabetic patients (NIDDM), who represented either the lowest (n = 14) or the highest (n = 18) quintiles of fasting plasma insulin. The higher plasma triglyceride level in the high insulin group (1.61 mmol/l vs. 0.87 mmol/l, P < 0.001) was due to multiple differences in triglyceride-rich lipoproteins. The concentrations of larger VLDL1, smaller VLDL2 particles, and IDL particles were 3.8-fold, 2.5-fold, and 1.5-fold higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In addition, hyperinsulinemic subjects had VLDL1, VLDL2, and IDL particles enriched in lipids and poor in protein. The lower plasma HDL cholesterol level in the high insulin group (1.20 mmol/l vs. 1.44 mmol/l, P < 0.01) compared to the low insulin group was a consequence of a 27% reduction of HDL2a concentration (P < 0.05) and a significantly reduced percentage of cholesterol in HDL3a, HDL3b, and HDL3c subclasses. On the other hand, the percentages of triglycerides in HDL2b, HDL2a, HDL3a, and HDL3b subclasses were 76%, 79%, 61%, and 50% higher, respectively, in the high insulin group than in the low insulin group (P < 0.01 or less). In the combined group, the concentration of VLDL1 and VLDL2 correlated positively with the concentrations of LDL2 and LDL3 and negatively with HDL2b and HDL2a subclasses (P < 0.05 or less). In conclusion, normolipidemic, glucose-tolerant but hyperinsulinemic relatives of NIDDM patients have qualitatively similar lipoprotein abnormalities as NIDDM patients. These abnormalities are not observed in insulin-sensitive relatives, suggesting that they develop in concert with insulin resistance. PMID:8827527

Tilly-Kiesi, M; Knudsen, P; Groop, L; Taskinen, M R

1996-07-01

105

Oxidized low-density lipoprotein biomarkers in atherosclerosis  

Microsoft Academic Search

The concept that the oxidation of lipoproteins is central in the pathogenesis of atherosclerosis was first reported over 25\\u000a years ago, initially by in vitro studies and subsequently through experimental models of atherosclerosis. The innate immune\\u000a system plays a key role in atherogenesis as manifested by its atherosclerosis-modulating properties, the immunogenicity of\\u000a oxidized low-density lipoprotein (LDL), and the presence of

Sotirios Tsimikas

2006-01-01

106

Lipopolysaccharide Is Transferred from High-Density to Low-Density Lipoproteins by Lipopolysaccharide-Binding Protein and Phospholipid Transfer Protein  

PubMed Central

Lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria, is a potent endotoxin that triggers cytokine-mediated systemic inflammatory responses in the host. Plasma lipoproteins are capable of LPS sequestration, thereby attenuating the host response to infection, but ensuing dyslipidemia severely compromises this host defense mechanism. We have recently reported that Escherichia coli J5 and Re595 LPS chemotypes that contain relatively short O-antigen polysaccharide side chains are efficiently redistributed from high-density lipoproteins (HDL) to other lipoprotein subclasses in normal human whole blood (ex vivo). In this study, we examined the role of the acute-phase proteins LPS-binding protein (LBP) and phospholipid transfer protein (PLTP) in this process. By the use of isolated HDL containing fluorescent J5 LPS, the redistribution of endotoxin among the major lipoprotein subclasses in a model system was determined by gel permeation chromatography. The kinetics of LPS and lipid particle interactions were determined by using Biacore analysis. LBP and PLTP were found to transfer LPS from HDL predominantly to low-density lipoproteins (LDL), in a time- and dose-dependent manner, to induce remodeling of HDL into two subpopulations as a consequence of the LPS transfer and to enhance the steady-state association of LDL with HDL in a dose-dependent fashion. The presence of LPS on HDL further enhanced LBP-dependent interactions of LDL with HDL and increased the stability of the HDL-LDL complexes. We postulate that HDL remodeling induced by LBP- and PLTP-mediated LPS transfer may contribute to the plasma lipoprotein dyslipidemia characteristic of the acute-phase response to infection.

Levels, J. H. M.; Marquart, J. A.; Abraham, P. R.; van den Ende, A. E.; Molhuizen, H. O. F.; van Deventer, S. J. H.; Meijers, J. C. M.

2005-01-01

107

Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations  

Microsoft Academic Search

In an attempt to characterize the in vivo behavior of (99mTc) low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of (99mTc)LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these

Shankar Vallabhajosula; Michael Paidi; Juan Jose Badimon; Ngoc-Anh Le; Stanley J. Goldsmith; Valentin Fuster; Henry N. Ginsberg

1988-01-01

108

Alterations in plasma lipids, lipoproteins and high density lipoprotein subfractions in peripheral arterial disease.  

PubMed

The concentrations of the major lipoprotein classes and of high density lipoprotein (HDL) subfractions in 63 male patients with arteriosclerosis of the lower limbs (claudication) were determined and compared with values from 63 healthy controls. The patients with peripheral arterial disease (PAD) had reduced levels of total HDL-cholesterol and HDL2b of large particle size, increased levels of small HDL3c particles and a high ratio of total plasma-cholesterol to HDL-cholesterol (coronary risk factor). The PAD patients, however, had lower levels of low density lipoprotein (LDL)-cholesterol but higher concentrations of very low density lipoprotein (VLDL)-cholesterol and plasma triglyceride than healthy subjects. This study therefore suggests that in PAD, the protective effect of HDL may be more important than the atherogenic effect of LDL. It further suggests that while HDL-cholesterol HDL2b and the ratio of total plasma-cholesterol to HDL-cholesterol may provide valid indices for identifying individuals at risk of PAD, other factors, such as LDL and total cholesterol, may not provide such an appropriate risk indicator. PMID:9199268

Mowat, B F; Skinner, E R; Wilson, H M; Leng, G C; Fowkes, F G; Horrobin, D

1997-06-01

109

Overexpression of human hepatic lipase and ApoE in transgenic rabbits attenuates response to dietary cholesterol and alters lipoprotein subclass distributions.  

PubMed

The effect of the expression of human hepatic lipase (HL) or human apoE on plasma lipoproteins in transgenic rabbits in response to dietary cholesterol was compared with the response of nontransgenic control rabbits. Supplementation of a chow diet with 0.3% cholesterol and 3.0% soybean oil for 10 weeks resulted in markedly increased levels of plasma cholesterol and VLDL and IDL in control rabbits as expected. Expression of either HL or apoE reduced plasma cholesterol response by 75% and 60%, respectively. The HL transgenic rabbits had substantial reductions in medium and small VLDL and IDL fractions but not in larger VLDL. LDL levels were also reduced, with a shift from larger, more buoyant to smaller, denser particles. In contrast, apoE transgenic rabbits had a marked reduction in the levels of large VLDLs, with a selective accumulation of IDLs and large buoyant LDLs. Combined expression of apoE and HL led to dramatic reductions of total cholesterol (85% versus controls) and of total VLDL+IDL+LDL (87% versus controls). HDL subclasses were remodeled by the expression of either transgene and accompanied by a decrease in HDL cholesterol compared with controls. HL expression reduced all subclasses except for HDL2b and HDL2a, and expression of apoE reduced large HDL1 and HDL2b. Extreme HDL reductions (92% versus controls) were observed in the combined HL+apoE transgenic rabbits. These results demonstrate that human HL and apoE have complementary and synergistic functions in plasma cholesterol and lipoprotein metabolism. PMID:10073966

Barbagallo, C M; Fan, J; Blanche, P J; Rizzo, M; Taylor, J M; Krauss, R M

1999-03-01

110

Recycling of vitamin E in human low density lipoproteins  

Microsoft Academic Search

Oxidative modification of low density lipoproteins (LDL) and their unrestricted scavenger receptordependent uptake is believed to account for cholesterol deposition in macrophagederived foam cells. It has been suggested that vitamin E that is transported by LDL plays a critical role in protecting against LDL oxidation. We hypothesize that the maintenance of sufficiently high vitamin E concentrations in LDL can be

Elena A. Serbinova; Trudy Forte; Giorgio Scita; Lester Packer

111

The significance of plasma high density lipoprotein cholesterol (hdlc)  

Microsoft Academic Search

High Density Lipoprotein (HDL) transports in plasma, phospholipids, cholesterol, and triacylglycerol. The cholesterol associated with HDL (HDLc) is cholesterol that is scavenged from peripheral tissues back t o liver. The liver converts this cholesterol into bil e acids, bile salts, and esterifies the rest and se cretes them into bile. Low HDLc is a risk factor for atherogene sis. Higher

Suprita Gupta; Ganapathy Rajagopal

112

Oxygen-Mediated Heterogeneity of Apo-Low-Density Lipoprotein  

Microsoft Academic Search

Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate\\/ polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of

Joseph Schuh; Gordon F. Fairclough; Rudy H. Haschemeyer

1978-01-01

113

High-density lipoproteins put out the fire.  

PubMed

Macrophages in atherosclerotic plaques are activated, inflammatory cells that directly contribute to the disease process. De Nardo et al. (2013), now report that high-density lipoproteins (HDL) can reprogram macrophages to be less inflammatory through an ATF3-dependent pathway, providing another mechanistic basis for the atheroprotective properties of HDL. PMID:24506861

Moore, Kathryn J; Fisher, Edward A

2014-02-01

114

Low Density Lipoprotein Undergoes Oxidative Modification in vivo  

Microsoft Academic Search

It has been proposed that low density lipoprotein (LDL) must undergo oxidative modification before it can give rise to foam cells, the key component of the fatty streak lesion of atherosclerosis. Oxidation of LDL probably generates a broad spectrum of conjugates between fragments of oxidized fatty acids and apolipoprotein B. We now present three mutually supportive lines of evidence for

Wulf Palinski; Michael E. Rosenfeld; Seppo Yla-Herttuala; Geoff C. Gurtner; Steve S. Socher; Susan W. Butler; Sampath Parthasarathy; Thomas E. Carew; Daniel Steinberg; Joseph L. Witztum

1989-01-01

115

Food product suitable for reducing low density lipoprotein cholesterol levels  

US Patent & Trademark Office Database

A food product suitable for reducing low density lipoprotein cholesterol levels comprising an amount of soy protein of at least 5 grams per average serving and at least 5 mg/kg statins is described. Preferably the food product comprises a fermented soy ingredient.

2005-02-01

116

Specific Recognition of Low Density Lipoprotein subspecies from Hypertriglyceridemic Subjects by a Monoclonal Antibody.  

National Technical Information Service (NTIS)

The authors have tested the reactivity of an anti-apoliprotein B monoclonal antibody (IVA5) with plasma low density lipoprotein (LSL) from patients with hypertriglyceridemia (HTG). Keywords: Monoclonal antibodies; Low density Lipoprotein; Reprints.

R. Cubicciotti R. M. Krauss A. E. Karu

1984-01-01

117

21 CFR 866.5600 - Low-density lipoprotein immunological test system.  

Code of Federal Regulations, 2010 CFR

... Immunological Test Systems § 866.5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by...

2009-04-01

118

21 CFR 866.5600 - Low-density lipoprotein immunological test system.  

Code of Federal Regulations, 2010 CFR

... Immunological Test Systems § 866.5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by...

2010-04-01

119

Low-density lipoprotein analysis in microchip capillary electrophoresis systems.  

PubMed

Due to the mounting evidence for altered lipoprotein and cholesterol-lipoprotein content in several disease states, there has been an increasing interest in analytical methods for lipoprotein profiling for diagnosis. The separation of low- and high-density lipoproteins (LDL and HDL, respectively) has been recently demonstrated using a microchip capillary electrophoresis (CE) system [1]. In contrast to this previous study, the present report demonstrates that LDL analysis can be performed in an uncoated glass microchannel. Moreover, by adding sodium dodecyl sulfate (SDS) to the sample at a concentration well below the critical micellar concentration prior to injection, the LDL peak undergoes a focusing effect and exhibits an apparent efficiency of 2.2 x 10(7) plates/m. Laser light scattering experiments demonstrate that the low concentration of SDS used does not significantly alter lipoprotein particle size distribution within the time course that the analysis is performed. It is thus hypothesized that SDS nondisruptively coats LDL particles. The peak sharpening effect, observed only when SDS is added solely to the sample, is probably due to a mobility gradient created between the sample and the running buffer. The chip-based method demonstrated here has the potential for rapid analysis and sensitive detection of different LDL forms of clinical relevance. PMID:12412132

Ceriotti, Laura; Shibata, Takayuki; Folmer, Britta; Weiller, Bruce H; Roberts, Matthew A; de Rooij, Nico F; Verpoorte, Elisabeth

2002-10-01

120

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

SciTech Connect

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

Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.; Garrett, Elizabeth; Otvos, James; Knight-Gibson, Carolyn; Alaupovic, Petar; Forte, Trudy; Farwig, Zachlyn N.; Macfarlane, Ronald D.

2003-10-01

121

Native High Density Lipoproteins (HDL) Interfere with Platelet Activation Induced by Oxidized Low Density Lipoproteins (OxLDL)  

PubMed Central

Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL) play a central role in the development of this disease, high density lipoproteins (HDL) represent an atheroprotective factor of utmost importance. As platelet function is remarkably sensitive to the influence of plasma lipoproteins, it was the aim of this study to clarify if HDL are able to counteract the stimulating effects of OxLDL with special emphasis on aspects of platelet function that are relevant to inflammation. Therefore, HDL were tested for their ability to interfere with pro-thrombotic and pro-inflammatory aspects of platelet function. We are able to show that HDL significantly impaired OxLDL-induced platelet aggregation and adhesion. In gel-filtered platelets, HDL decreased both the formation of reactive oxygen species and CD40L expression. Furthermore, HDL strongly interfered with OxLDL-induced formation of platelet-neutrophil aggregates in whole blood, suggesting that platelets represent a relevant and sensitive target for HDL. The finding that HDL effectively competed with the binding of OxLDL to the platelet surface might contribute to their atheroprotective and antithrombotic properties.

Badrnya, Sigrun; Assinger, Alice; Volf, Ivo

2013-01-01

122

High-Density Lipoproteins and the Immune System  

PubMed Central

High-density lipoprotein (HDL) plays a major role in vasodilation and in the reduction of low-density lipoprotein (LDL) oxidation, inflammation, apoptosis, thrombosis, and infection; however, HDL is now less functional in these roles under certain conditions. This paper focuses on HDL, its anti-inflammation behavior, and the mechanisms by which HDL interacts with components of the innate and adaptive immune systems. Genome-wide association studies (GWAS) and proteomic studies have elucidated important molecules involved in the interaction between HDL and the immune system. An understanding of these mechanisms is expected to be useful for the prevention and treatment of chronic inflammation due to metabolic syndrome, atherosclerosis, or various autoimmune diseases.

Kaji, Hidesuke

2013-01-01

123

Cigarette smoke extract inhibits oxidative modification of low density lipoprotein  

Microsoft Academic Search

Oxidative modification of low density lipoprotein (LDL) by cigarette smoke has been suggested in several recent studies. To characterize possible modification of LDL by cigarette smoke extract (CSE), we incubated LDL with CSE either in the presence or absence of the chemical pro-oxidants, cupric chloride or 2,2?-azo-bis(2-amidinopropane) hydrochloride (AAPH). Surprisingly, CSE inhibited oxidative modification of LDL induced by either copper

Chen Chen; George Loo

1995-01-01

124

Low-Density Lipoprotein Cholesterol and Coronary Artery Disease  

Microsoft Academic Search

Except for age, dyslipidemia is the most important predictive factor for coronary artery disease (CAD) (1). The strong, independent, continuous, and graded relationship between total cholesterol (TC) levels, or low-density lipoprotein\\u000a (LDL)-cholesterol (C) level and the risk of CAD events has been clearly demonstrated world wide in men and women and in all\\u000a age groups (2–6). High cholesterol levels are

JoAnne Micale Foody

125

High Density Lipoprotein Particle Size in Children: Relation to Atherogenic Dyslipidemia  

PubMed Central

Atherosclerosis begins in childhood. Protection from atherosclerosis is provided by high-density lipoprotein (HDL), a heterogeneous particle, which includes several subclasses differing in size, density and apolipoprotein content. The objective of this study was to document the relevance of assessing HDL particle size as another feature of dyslipidemia related to the develpment of atheosclerosis during childhood. For that purpose, HDL particle size in 268 community-based children (137 boys and 131 girls), 7–13 years old, was measured by gradient gel electrophoresis, and relationships of HDL particle size to plasma lipids parameters and the anthropometric indices were analyzed. There was no gender difference in HDL particle diameter. The results of analysis revealed significant positive correlations between HDL particle diameter and HDL-cholesterol level (r=0.363, p<0.01), apolipoprotein AI level (r=0.310, r<0.05) and low-density lipoprotein particle (LDL) size (r=0.290, p<0.05), while there was an inverse correlation with atherogenic index (r=–0.316, p<0.05). There was no significant correlation between HDL particle size and triglyceride levels in the overall analysis (n=268), however, when this relation was analyzed in the limited HDL size range below 11 nm, a significant inverse relation appeared between particle size and TG levels (r =–0.546, P<0.01, n=75). These findings indicate that the general shift toward smaller HDL particle size was associated with dyslipidemia characterized by higher atherogenic index and triglyceride level, lower HDL-C level and smaller LDL particle size. Therefore, HDL size may represent another relevant marker of atherogenic lipid metabolism.

Numata, Michio

2004-01-01

126

High-density lipoproteins and cerebrovascular integrity in Alzheimer's disease.  

PubMed

Cerebrovascular dysfunction significantly contributes to the clinical presentation and pathoetiology of Alzheimer's disease (AD). Deposition and aggregation of ?-amyloid (A?) within vascular smooth muscle cells leads to inflammation, oxidative stress, impaired vasorelaxation, and disruption of blood-brain barrier integrity. Midlife vascular risk factors, such as hypertension, cardiovascular disease, diabetes, and dyslipidemia, increase the relative risk for AD. These comorbidities are all characterized by low and/or dysfunctional high-density lipoproteins (HDL), which itself is a risk factor for AD. HDL performs a wide variety of critical functions in the periphery and CNS. In addition to lipid transport, HDL regulates vascular health via mediating vasorelaxation, inflammation, and oxidative stress and promotes endothelial cell survival and integrity. Here, we summarize clinical and preclinical data examining the involvement of HDL, originating from the circulation and from within the CNS, on AD and hypothesize potential synergistic actions between the two lipoprotein pools. PMID:24508505

Stukas, Sophie; Robert, Jérôme; Wellington, Cheryl L

2014-04-01

127

Pharmacologic management of isolated low high-density lipoprotein syndrome.  

PubMed

High-density lipoprotein (HDL) cholesterol is a heterogeneous group of lipoproteins exhibiting a variety of properties like prostacyclin production stimulation, decrease in platelet aggregation, endothelial cell apoptosis inhibition, and low-density lipoprotein oxidation blockade. Epidemiologic studies have shown an inverse relation between HDL cholesterol levels and cardiovascular risk. Low HDL cholesterol is associated with increased risk for myocardial infarction, stroke, sudden death, peripheral artery disease, and postangioplasty restenosis. In contrast, high HDL levels are associated with longevity and protection against atherosclerotic disease development. Given the evolving epidemic of obesity, diabetes mellitus, and metabolic syndrome, the prevalence of low HDL will continue to rise. In the United States, low HDL is present in 35% of men, 15% of women, and approximately 63% of patients with coronary artery disease. Data extracted from the Framingham study highlight that 1-mg increase in HDL levels decreases by 2% to 3% the risk of cardiovascular disease. There is no doubt regarding clinical importance about isolated low HDL, but relatively few clinicians consider a direct therapeutic intervention of this dyslipidemia. In this sense, lifestyle measures should be the first-line strategy to manage low HDL levels. On the other hand, pharmacologic options include niacin, fibrates, and statins. Fibrates appear to reduce risk preferentially in patients with low HDL with metabolic syndrome, whereas statins reduce risk across all levels of HDL. Torcetrapib, a cholesteryl esters transfer protein inhibitor, represented a hope to raise this lipoprotein; however, all clinical trials on this drug had ceased after ILLUMINATE, RADIANCE and ERASE trials had recorded an increase in mortality, rates of myocardial infarction, angina, and heart failure. In the near future, drugs as beta-glucans, Apo-A1 mimetic peptides, and ACAT inhibitors, are the new promises to treat this condition. PMID:18645343

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

2008-01-01

128

Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity.  

PubMed Central

A cDNA that expresses a receptor for very low density lipoprotein (VLDL) was isolated from a rabbit heart cDNA library and characterized. The deduced amino acid sequence of the cDNA revealed that the cDNA encodes a protein with striking homology to the low density lipoprotein (LDL) receptor. Like the LDL receptor, the mature protein consists of the following five domains spanning 846 amino acids: 328 N-terminal amino acids including an 8-fold repeat of 40 amino acids homologous to the ligand binding repeat of the LDL receptor; 396 amino acid residues homologous to the epidermal growth factor precursor including three cysteine-rich repeats; a region immediately outside of the plasma membrane rich in serines and threonines; 22 amino acids traversing the plasma membrane; and 54 amino acids including the NPVY sequence that is required for clustering of the LDL receptor in coated pits and that projects into the cytoplasm. LDL-receptor-deficient Chinese hamster ovary cells transfected with the cDNA bound and internalized VLDL, beta-migrating VLDL, and intermediate density lipoprotein but did not bind LDL with high affinity. The 3.6- and 9.5-kilobase mRNAs for the VLDL receptor are highly abundant in heart, muscle, and adipose tissue. Barely detectable amounts of the mRNAs were present in liver. Based on the structural features, ligand specificity, and tissue expression of the mRNAs, we suggest that this VLDL receptor may mediate uptake of apolipoprotein E-containing lipoproteins enriched with triglyceride in nonhepatic tissues that are active in fatty acid metabolism. Images

Takahashi, S; Kawarabayasi, Y; Nakai, T; Sakai, J; Yamamoto, T

1992-01-01

129

A Mediterranean-style, low-glycemic-load diet decreases atherogenic lipoproteins and reduces lipoprotein (a) and oxidized low-density lipoprotein in women with metabolic syndrome.  

PubMed

The objective was to assess the impact of a Mediterranean-style, low-glycemic-load diet (control group, n = 41) and the same diet plus a medical food (MF) containing phytosterols, soy protein, and extracts from hops and Acacia (MF group, n = 42) on lipoprotein atherogenicity in women with metabolic syndrome. Plasma lipids, apolipoproteins (apos), lipoprotein subfractions and particle size, low-density lipoprotein (LDL) oxidation, and lipoprotein (a) were measured at baseline, week 8, and week 12 of the intervention. Three-day dietary records were collected at the same time points to assess compliance. Compared with baseline, women decreased energy intake from carbohydrate (P < .001) and fat (P < .001), whereas they increased energy intake from protein (P < .001). A significant increase in energy from monounsaturated fatty acids was also observed as well as increases in eicosapentaenoic acid and docosahexaenoic acid, whereas trans-fatty acid intake was reduced (P < .00001). The atherogenic lipoproteins, large very low-density lipoprotein (P < .0001) and small LDL (P < .0001), were reduced, whereas the ratio of large high-density lipoprotein to smaller high-density lipoprotein particles was increased (P < .0001). Apolipoprotein B was reduced for all women (P < .0001), with a greater reduction in the MF group (P < .025). Oxidized LDL (P < .05) and lipoprotein (a) (P < .001) were reduced in both groups at the end of the intervention. Consumption of a Mediterranean-style diet reduces the risk for cardiovascular disease by decreasing atherogenic lipoproteins, oxidized LDL, and apo B. Inclusion of an MF may have an additional effect in reducing apo B. PMID:21944261

Jones, Jennifer L; Comperatore, Michael; Barona, Jacqueline; Calle, Mariana C; Andersen, Catherine; McIntosh, Mark; Najm, Wadie; Lerman, Robert H; Fernandez, Maria Luz

2012-03-01

130

Genes Associated with Low Serum High-density Lipoprotein Cholesterol.  

PubMed

Atherosclerosis is the main cause of death in the world through causing ischemic heart disease (IHD). Altered serum lipid level is the most important risk factor for coronary artery disease (CAD). Many studies reveal a strong inverse association between low levels of high density lipoprotein cholesterol (HDL-C) and increased risk of IHD. On the other hand, plasma levels of HDL-C has a strong hereditary basis. This review focuses on recent data about genetic defects that reduce the level of HDL-C. In order to investigate possible genes linked to low HDL-C disorder, we reviewed previous studies; we searched current medical literature from September 1990 through January 2013 for the genetics causes of low HDL-C levels. Genetic defects in ATP binding cassette protein (ABCA1), apolipoprotein (APO) A1, lecithin cholesteryl acyl transferase, Lipoprotein lipase (LPL), and angiopoietin-like 3 proteins (ANGPTL3) associated with low HDL-C. Other potentially important candidates involved in low HDL-C syndromes are metabolic disorders including sphingomyelin phosphodiesterase 1 and glucocerebrosidase. Also Molecular variations in many genes such as ABCAI and APOAI, TRIB1 and Apo E, lipoprotein lipase (LPL), WW domain-containing oxidoreductase (WWOX), Hepatic lipase (HL), lecithin cholesteryl acyl transferase and some linkage analysis have been associated with reduced HDL-Status. Low HDL-C syndrome has a strong genetic basis and is correlated with an increased risk of CAD. PMID:24916532

Ahmadzadeh, Alireza; Azizi, Fereidoun

2014-06-01

131

Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic.  

PubMed

Free radicals are believed to be involved in leukocyte induced tissue injury. The present studies were performed to determine whether low density lipoprotein (LDL) might serve as a mediator of tissue injury after leukocyte induced free radical oxidation of LDL. Our results show that incubation of LDL with monocytes or polymorphonuclear leukocytes (PMN) leads to oxidation of the lipoprotein rendering it toxic to proliferating fibroblasts. Monocyte activation enhances these effects. Butylated hydroxytoluene (BHT), vitamin E (vit E) and glutathione (GSH) virtually prevent the oxidation of LDL and the formation of cytotoxic LDL, indicating that these alterations are mediated by leukocyte-derived free radicals. This is the first demonstration that short-lived free radicals emanating from phagocytic cells could mediate cell injury through the action of a stable cytotoxin formed by the oxidation of LDL. The fact that lipoproteins can transfer a cytotoxic effect from leukocytes to proliferating cells reveals a pathway for cell destruction which may have implications in atherosclerotic plaque progression, macrophage mediated toxicity to tumor cells and tissue injury by inflammatory processes. PMID:3861749

Cathcart, M K; Morel, D W; Chisolm, G M

1985-08-01

132

Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery.  

PubMed

We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy that combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy, and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

McMahon, Kaylin M; Mutharasan, R Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K; Luthi, Andrea J; Helfand, Brian T; Ardehali, Hossein; Mirkin, Chad A; Volpert, Olga; Thaxton, C Shad

2011-03-01

133

High-Density Lipoprotein: Is the Good Cholesterol Turning Bad?  

Microsoft Academic Search

Low high-density lipoprotein cholesterol (HDL-C) is the most prevalent lipid abnormality in patients with known coronary heart\\u000a disease (CHD). Since the 1960 s, epidemiologic studies have shown an inverse relationship between HDL-C levels and risk of\\u000a developing CHD. This data correlates a 1-mg\\/dL increase in HDL-C with a 2% to 3% reduction in CHD events. The prevalence of\\u000a low HDL-C among

Aysha Inankur; Stephen J. Nicholls; Anisa Jahangiri

2011-01-01

134

Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery  

PubMed Central

We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy which combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy (TEM), and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery.

McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga; Thaxton, C. Shad

2014-01-01

135

[The impact of a 14-?day regular physical exercise regime on the concentration of the classes and subclasses of lipoprotein particles in young subjects with a sedentary lifestyle].  

PubMed

Recommendations from the cardiological professional companies working in the area of primary prevention of cardiovascular diseases put an emphasis on regular aerobic physical activity. Its positive effect on both cardiovascular and overall mortality has repea-tedly been proven by the observations of prospective and cross?sectional epidemiological studies. One of the possible explanations of this positive effect is a change in the concentration of lipoprotein classes and their subclasses, which is expressed as a change in their average size. In a group of young healthy men and women with a sedentary lifestyle we observed the effect of medium intensive physical exercise in the form of a 30-?minute slow run per day lasting for 14 days. The concentration of lipoprotein classes and subclasses were determined through the method of a linear electrophoresis in polyacrylamide gel. In the observed group we found a statistically significant decrease of VLDL, large IDL particles, medium sized LDL, small dense LDL, and medium sized HDL particles. In the light of current knowledge all these lipoprotein particles are deemed as atherogenic. Thus, as little as 14 days of regular exercising has a positive effect on the concentration of plasmatic lipoproteins, and emphasises the role of regular physical activity in the primary prevention of cardiovascular diseases. PMID:24164365

Sabaka, P; Dukát, A; Oravec, S; Mistríková, L; Baláž, D; Bendžala, M; Gašpar, L

2013-10-01

136

Structural and functional assessment of high-density lipoprotein heterogeneity.  

PubMed

We studied the heterogeneity of high-density lipoproteins (HDL) in plasma of 110 subjects, using three different methods: (a) gradient gel electrophoresis (GGE); (b) electroimmunoassay, to measure the concentration of lipoprotein particles containing apoprotein (apo) AI but no apo-AII (LP AI); and (c) cholesterol esterification rate (FERHDL) in very-low- and low-density lipoprotein-depleted plasma. There were two study groups: patients with hypertension, whose plasma lipid profile was similar to their respective controls, and patients with hypoalphalipoproteinemia (hypoalpha), whose family members served as controls. Values for FERHDL were significantly higher in both risk groups than in their respective controls. LP AI was significantly decreased only in the hypoalpha subjects. Generally, LP AI and FERHDL were inversely related. LP AI correlated strongly with plasma HDL-cholesterol, apo AI, and LP AI/AII; FERHDL correlated with those values inversely. LP AI, but not FERHDL, correlated with HDL free cholesterol. On the other hand, FERHDL correlated strongly with plasma concentrations of triglycerides and with the plasma ratio of total/HDL-cholesterol while LP AI did not. GGE determination of the composition of HDL subspecies showed that both FERHDL and LP AI were significantly related to the content of HDL2b particles: FERHDL inversely, LP AI directly; the relative amount of HDL3b,c particles correlated only with FERHDL. We conclude that GGE and FERHDL can be used to quantify both the apparently protective (HDL2b) and risk-associated (HDL3b,c) particles, whereas the concentration of LP AI in plasma mainly reflects the concentration of the HDL2 subpopulation. PMID:8044996

Dobiásová, M; Frohlich, J J

1994-08-01

137

High-density lipoprotein subpopulations as substrates for the transfer of cholesteryl esters to very-low-density lipoproteins.  

PubMed Central

1. Human total HDL (high-density lipoprotein), HDL2 and HDL3 were labelled in vitro by incubation with lipoprotein-deficient serum (LPDS) which contained either [3H]cholesteryl oleate or [14C]cholesterol under different conditions. The lipoproteins were then subfractionated by heparin-Sepharose column chromatography, and three subfractions (A, B and C) were successively eluted from each preparation of HDL, HDL2 and HDL3. When the labelling was done at 37 degrees C for 17 h, the subfractions were homogeneously labelled with [3H]cholesteryl oleate. However, when it was performed for only 30 min at 4 degrees C, the subfractions showed marked differences in the 3H specific radioactivity, which was much higher in the C fractions than in the others. 2. 3H-labelled HDL2 and HDL3 subfractions behaved differently under the precipitant action of heparin-Mn2+; fraction C (the richest in apolipoprotein E) produced the largest amount of radioactive and chemical precipitate. More 3H radioactivity, but not the cholesterol, was precipitated from HDL2 or HDL3 by the reagent, demonstrating that 3H-labelled HDL2 and HDL3 behave like their fraction C, which becomes labelled to the highest specific radioactivity despite having the smallest mass. 3. The incubation of 3H-labelled HDL subfractions with human LPDS and very-low-density lipoprotein (VLDL) at 37 degrees C increased the quantity of 3H radioactivity that was precipitated, in proportion to the amount of VLDL present in the media. These changes were attributable to the action of cholesterol ester transfer protein, since they did not occur at 4 degrees C or when human LPDS was replaced with rat LPDS. 4. Kinetics of the transfer of HDL [3H]cholesteryl oleate to VLDL showed a greater apparent Vmax for fractions A than for fractions B from either HDL2 or HDL3, whereas the apparent Km values were very similar, which suggest that this transfer process is influenced by the apoprotein composition of the donor lipoprotein. Images Fig. 2.

Lasuncion, M A; Iglesias, A; Skottova, N; Orozco, E; Herrera, E

1990-01-01

138

Hepatic apo E expression is required for remnant lipoprotein clearance in the absence of the low density lipoprotein receptor.  

PubMed Central

According to the secretion-capture model of remnant lipoprotein clearance, apo E secreted by hepatocytes into the space of Disse serves to enrich the remnants with a ligand for receptor-mediated lipoprotein endocytosis. Current evidence supports a two-receptor model of lipoprotein removal, in which apo E-containing remnants bind either the low density lipoprotein receptor (LDLR) or the LDLR-related protein (LRP). Recently, we demonstrated that reconstitution of apo E(-/-) mice with apo E(+/+) marrow results in normalization of plasma lipoprotein levels, indicating that hepatic expression of apo E is not required for remnant clearance and calling into question the relevance of the secretion-capture mechanism. To dissect the relative contributions of LDLR and LRP to the cellular catabolism of remnant lipoproteins by the hepatocyte, bone marrow transplantation (BMT) was used to reconstitute macrophage expression of apo E in mice that were null for expression of both apo E and the LDLR. Reconstitution of macrophage apo E in apo E(-/-)/LDLR(-/-) mice had no effect on serum lipid and lipoprotein concentrations, although it produced plasma apo E levels up to 16-fold higher than in C57BL/6 controls. Immunocytochemistry of hepatic sections revealed abundant staining for apo E in the space of Disse, but no evidence of receptor-mediated endocytosis of remnant lipoproteins. Transient expression of human LDLR in the livers of apo E(+/+)--> apo E(-/-)/LDLR(-/-) mice by adenoviral gene transfer resulted in normalization of serum lipid levels and in the clearance of apo E-containing lipoproteins from the space of Disse. We conclude that whereas the LDLR efficiently clears remnant lipoproteins irrespective of the site of origin of apo E, endocytosis by the chylomicron remnant receptor (LRP) is absolutely dependent on hepatic expression of apo E. These data demonstrate in vivo the physiologic relevance of the apo E secretion-capture mechanism in the liver.

Linton, M F; Hasty, A H; Babaev, V R; Fazio, S

1998-01-01

139

High-density lipoprotein functionality in coronary artery disease.  

PubMed

: The role of high-density lipoprotein (HDL) in cardiovascular atheroprotection is well established. Epidemiological data have clearly demonstrated an inverse relationship between HDL levels and the risk for coronary artery disease, which is independent of the low-density lipoprotein levels. However, more recent data provide evidence that high HDL levels are not always protective and that under certain conditions may even confer an increased risk. Thus, a new concept has arisen, which stresses the importance of HDL functionality, rather than HDL concentration per se, in the assessment of cardiovascular risk. HDL functionality is genetically defined but can also be modified by several environmental and lifestyle factors, such as diet, smoking or certain pharmacologic interventions. Furthermore, HDL is consisted of a heterogeneous group of particles with major differences in their structural, biological and functional properties. Recently, the cholesterol efflux capacity from macrophages was proven to be an excellent metric of HDL functionality, because it was shown to have a strong inverse relationship with the risk of angiographically documented coronary artery disease, independent of the HDL and apolipoprotein A-1 levels, although it may not actually predict the prospective risk for cardiovascular events. Thus, improving the quality of HDL may represent a better therapeutic target than simply raising the HDL level, and assessment of HDL function may prove informative in refining our understanding of HDL-mediated atheroprotection. PMID:24603157

Kosmas, Constantine E; Christodoulidis, Georgios; Cheng, Jeh-Wei; Vittorio, Timothy J; Lerakis, Stamatios

2014-06-01

140

Intracellular Trafficking and Secretion of Very Low Density Lipoproteins  

PubMed Central

Steady increase in the incidence of atherosclerosis is becoming a major concern not only in the United States but also in other countries. One of the major risk factors for the development of atherosclerosis is high concentrations of plasma low density lipoprotein (LDL), which are metabolic products of very low density lipoprotein (VLDL). VLDLs are synthesized and secreted by the liver. In this review, we discuss various stages through which VLDL particles go from their biogenesis to secretion in the circulatory system. Once VLDLs are synthesized in the lumen of the endoplasmic reticulum (ER), they are transported to the Golgi. The transport of nascent VLDLs from the ER to Golgi is a complex multi-step process, which is mediated by a specialized transport vesicle, the VLDL transport vesicle (VTV). The VTV delivers VLDLs to the cis-Golgi lumen where nascent VLDLs undergo a number of essential modifications. The mature VLDL particles are then transported to the plasma membrane and secreted in the circulatory system. Understanding of molecular mechanisms and identification of factors regulating the complex intracellular VLDL trafficking will provide insight into the pathophysiology of various metabolic disorders associated with abnormal VLDL secretion and identify potential new therapeutic targets.

Tiwari, Samata; Siddiqi, Shadab A.

2012-01-01

141

Distinct Hepatic Receptors for Low Density Lipoprotein and Apolipoprotein E in Humans  

NASA Astrophysics Data System (ADS)

Since the liver is a central organ for lipid and lipoprotein synthesis and catabolism, hepatic receptors for specific apolipoproteins on plasma lipoproteins would be expected to modulate lipid and lipoprotein metabolism. The role of hepatic receptors for low density lipoproteins and apolipoprotein E-containing lipoproteins was evaluated in patients with complementary disorders in lipoprotein metabolism: abetalipoproteinemia and homozygous familial hypercholesterolemia. In addition, hepatic membranes from a patient with familial hypercholesterolemia were studied and compared before and after portacaval shunt surgery. The results establish that the human liver has receptors for apolipoproteins B and E. Furthermore, in the human, hepatic receptors for low density lipoproteins and apolipoprotein E are genetically distinct and can undergo independent control.

Hoeg, Jeffrey M.; Demosky, Stephen J.; Gregg, Richard E.; Schaefer, Ernst J.; Brewer, H. Bryan

1985-02-01

142

Role of oxidized low-density lipoprotein in the atherosclerosis of uremia  

Microsoft Academic Search

Role of oxidized low-density lipoprotein in the atherosclerosis of uremia. Lipoprotein oxidation is involved in the genesis of atherosclerosis. In chronic renal failure (CRF), oxidative stress is enhanced because of an imbalance between pro-oxidant and antioxidant systems. Oxidative modifications of low-density lipoproteins (LDLs) occur not only at the level of lipid moiety, but also of protein moiety. We have shown

Tilman B. Drueke; THAO NGUYEN KHOA; Ziad A. Massy; VÉRONIQUE WITKO-SARSAT; BERNARD LACOUR; BÉATRICE DESCAMPS-LATSCHA

2001-01-01

143

Isolation of high density lipoproteins from rat intestinal epithelial cells.  

PubMed Central

Previous studies have defined forms of high density lipoproteins (HDL) in rat mesenteric lymph, suggesting that they have a secretory origin. This study describes the isolation and characterization of intestinal intracellular HDL. Two preparations were made as follows: (a) Rat enterocytes were isolated and a Golgi organelle fraction was prepared. (b) Cell homogenates were subjected to nitrogen cavitation and a cytoplasmic fraction was prepared. Lipoproteins were isolated from both preparations by sequential ultracentrifugation. When the HDL fraction (1.07-1.21 g/ml) was subjected to isopyknic density gradient ultracentrifugation, a peak of apoproteins A-I and B (apoA-I and apoB, respectively) was found at a density of 1.11-1.14 g/ml. Electron microscopy of the fraction showed spherical particles ranging in size from 6 to 13 nm. Immunoelectrophoresis revealed a precipitin arc in the alpha region against apoA-I which extended into the pre-beta region where a precipitin arc against apoB was also seen. ApoB antisera depleted the pre-beta particles whereas the alpha migrating particles remained. Lipid analysis of the whole HDL fraction revealed phospholipid, cholesteryl ester, and triglyceride as the major lipids. [3H]leucine was then administered into the duodenum and a radiolabeled intracellular HDL fraction was isolated. The newly synthesized apoproteins of the HDL fraction, as determined by gel electrophoresis, were apoB, apoA-I, and apolipoprotein A-IV (ApoA-IV). Immunoprecipitation of the apoB particles revealed apoA-I and apoA-IV in the supernatant. These data demonstrate that there are at least two intracellular intestinal forms of HDL particles, one of which contains apoB. The other particle contains apoA-I and apoA-IV, has alpha mobility, is spherical, and resembles a particle found in the lymph. Images

Magun, A M; Brasitus, T A; Glickman, R M

1985-01-01

144

Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes mellitus  

Microsoft Academic Search

Coronary artery disease (CAD) is a major cause of death in patients with insulin-dependent diabetes mellitus. Qualitative\\u000a changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) are thought to be important for evaluating the\\u000a risk for CAD. In the present study, we evaluated LDL particle size (LDL-size) by 2%–16% gradient gel electrophoresis, along\\u000a with conventional lipids and apolipoproteins,

T. Ohta; S. Nishiyama; T. Nakamura; K. Saku; K. K. Maung; I. Matsuda

1998-01-01

145

Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in patients with rheumatoid arthritis  

Microsoft Academic Search

Objectives. To analyse the association of autoantibodies against cardiolipin (CL) and oxidized low density lipoproteins wcopper-oxidized low density lipoprotein (oxLDL), malondialdehyde- modified LDL (MDA-LDL)x with rheumatoid arthritis (RA) and cardiovascular complications. Methods. One hundred and twenty-one patients with RA were consecutively included. Autoantibodies were determined by ELISA. Healthy individuals from the same region were used as controls. Results. Levels of

J. T. Cvetkovic; S. Wallberg-Jonsson; E. Ahmed; S. Rantapaa; A. K. Lefvert

2002-01-01

146

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements  

Microsoft Academic Search

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation\\u000a fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol\\u000a measurements. In vivo, the intravenous infusion of LEH (5.6 mL\\/kg, n=6) elevated serum triglycerides (+92% vs. baseline, PPP<.01) and had no effect on serum HDL cholesterol. In addition, LEH did

F. Abdullah; M. Whiteford; G. Mathiak; P. Ovadia; A. Rudolph; L. F. Neville; R. Rabinovici

1997-01-01

147

Oxidized low density lipoprotein, stem cells, and atherosclerosis.  

PubMed

Oxidized low density lipoprotein (ox-LDL), a risk factor of atherosclerosis, facilitates the formation and vulnerability of atherosclerotic plaque, thus contributing to several clinical complications. Stem cells participate in vascular repair after damage and atherosclerosis is a process of inflammation accompanied with vascular injury. Researchers have proposed that stem cells participate in the formation of atherosclerotic plaque. Also, because ox-LDL is capable of inducing toxic effects on stem cells, it is reasonable to postulate that ox-LDL promotes the progress of atherosclerosis via acting on stem cells. In the present article, we review the relationship between ox-LDL, stem cells, and atherosclerosis and a portion of the associated mechanisms. PMID:22747902

Yang, Hui; Mohamed, Ahmed Salah Salem; Zhou, Sheng-Hua

2012-01-01

148

High-Density Lipoprotein and Prostate Cancer: An Overview  

PubMed Central

Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. High-density lipoprotein cholesterol (HDL-C) has recently received much attention as a possible risk marker of prostate cancer development and prognosis. In the present article, we summarized findings from epidemiologic studies of the association between HDL-C and prostate cancer. Low HDL-C level was found to be a risk and prognostic factor of prostate cancer in several epidemiologic studies, although the overall linkage between HDL and prostate cancer has not been definitively established. The mechanisms for this association remain uncertain; however, limited data from experimental studies imply a possible role of HDL in the pathophysiology of prostate cancer. More epidemiologic research, in combination with experimental studies, is needed in this field.

Kotani, Kazuhiko; Sekine, Yoshitaka; Ishikawa, Shizukiyo; Ikpot, Imoh Z.; Suzuki, Kazuhiro; Remaley, Alan T.

2013-01-01

149

Effect of low-density lipoprotein cholesterol apheresis on blood viscosity.  

PubMed

Few studies have been designed to study the hemodynamic effects of low-density lipoprotein apheresis, especially on whole blood viscosity. Six patients with cardiovascular disease and hypercholesterolemia underwent a single low-density lipoprotein apheresis, resulting in significant reductions in whole blood viscosity at all shear rates. PMID:15081454

Moriarty, Patrick M; Gibson, Cheryl A; Kensey, Kenneth R; Hogenauer, William

2004-04-15

150

Effect of low-density lipoprotein cholesterol apheresis on blood viscosity  

Microsoft Academic Search

Few studies have been designed to study the hemodynamic effects of low-density lipoprotein apheresis, especially on whole blood viscosity. Six patients with cardiovascular disease and hypercholesterolemia underwent a single low-density lipoprotein apheresis, resulting in significant reductions in whole blood viscosity at all shear rates.

Patrick M. Moriarty; Cheryl A. Gibson; Kenneth R. Kensey; William Hogenauer

2004-01-01

151

Inhibition of Low Density Lipoprotein Synthesis by Dietary Omega3 Fatty Acids in Humans  

Microsoft Academic Search

Diets rich in omega-3 fatty acids derived from fish oils lower the plasma concentra- tions of low density lipoproteins (LDL) and very low density lipoproteins in humans. The present study was designed to examine the mechanism(s) by which diets en- riched in omega-3 fatty acids reduce plasma LDL cholesterol levels in normal sub- jects. Seven healthy volunteers with normal plasma

D. Roger Illingworth; William S. Harris; William E. Connor

2010-01-01

152

Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity  

Microsoft Academic Search

Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is

Peter O Kwiterovich

2002-01-01

153

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

ERIC Educational Resources Information Center

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

McCunney, Robert J.

1987-01-01

154

Identification of Scavenger Receptor SR-BI as a High Density Lipoprotein Receptor  

Microsoft Academic Search

High density lipoprotein (HDL) and low density lipoprotein (LDL) are cholesterol transport particles whose plasma concentrations are directly (LDL) and inversely (HDL) correlated with risk for atherosclerosis. LDL catabolism involves cellular uptake and degradation of the entire particle by a well-characterized receptor. HDL, in contrast, selectively delivers its cholesterol, but not protein, to cells by unknown receptors. Here it is

Susan Acton; Attilio Rigotti; Katherine T. Landschulz; Shangzhe Xu; Helen H. Hobbs; Monty Krieger

1996-01-01

155

Co-isolation of extracellular vesicles and high-density lipoproteins using density gradient ultracentrifugation  

PubMed Central

Extracellular vesicles (EVs) facilitate intercellular communication by carrying bioactive molecules such as proteins, messenger RNA, and micro (mi)RNAs. Recently, high-density lipoproteins (HDL) isolated from human plasma were also reported to transport miRNA to other cells. HDL, when isolated from human plasma, ranges in density between 1.063 and 1.21 g/mL, which grossly overlap with the reported density of EVs. Consequently, HDL and EV will be co-isolated when using density gradient ultracentrifugation. Thus, more stringent isolation/separation procedures of EV and HDL are essential to know their relative contribution to the pool of circulating bioactive molecules.

Yuana, Yuana; Levels, Johannes; Grootemaat, Anita; Sturk, Auguste; Nieuwland, Rienk

2014-01-01

156

Effect of cell density on binding and uptake of low density lipoprotein by human fibroblasts  

PubMed Central

The effect of cell density on low density lipoprotein (LDL) binding by cultured human skin fibroblasts was investigated. Bound LDL was visualized by indirect immunofluorescence. Cellular lipid and cholesterol were monitored by fluorescence in cells stained with phosphine 3R and filipin, respectively. LDL binding and lipid accumulation were compared in cells in stationary and exponentially growing cultures, in sparsely and densely plated cultures, in wounded and non-wounded areas of stationary cultures, and in stationary cultures with and without the addition of lipoprotein-deficient serum. We conclude that LDL binding and cholesterol accumulation induced by LDL are influenced by cell density. It appears that, compared to rapidly growing cells, quiescent (noncycling) human fibroblasts exhibit fewer functional LDL receptors.

1979-01-01

157

Decreased high-density lipoprotein cholesterol levels in polyarticular juvenile idiopathic arthritis  

PubMed Central

OBJECTIVES: To investigate the prevalence of dyslipoproteinemia in a homogeneous cohort of polyarticular juvenile idiopathic arthritis patients. METHODS: Based on the National Cholesterol Education Program, fasting lipoprotein levels and risk levels for coronary artery disease were determined in 28 patients with polyarticular juvenile idiopathic arthritis. The exclusion criteria included diabetes, thyroid dysfunction, smoking, proteinuria, lipid-lowering drugs, and hormone/diuretic therapy. Disease activity, disease duration, and therapy with corticosteroids and/or chloroquine were defined at the time of lipid measurements. RESULTS: Dyslipoproteinemia was identified in 20 of the 28 (71%) patients with polyarticular juvenile idiopathic arthritis. The primary lipoprotein risk factor was decreased high-density lipoprotein cholesterol (57%), followed by elevated levels of low-density lipoprotein cholesterol (18%), triglycerides (14%), and total cholesterol (7%). The male patients had decreased high-density lipoprotein cholesterol levels than the female patients (p<0.05). The incidence of decreased high-density lipoprotein cholesterol levels did not seem to be affected by disease activity or therapy because the incidence was similar in patients with active or inactive disease, with or without corticosteroid use and with or without chloroquine use. In addition, the frequency of decreased high-density lipoprotein cholesterol levels was similar in patients with short (?5 years) vs. long (>5 years) disease duration. CONCLUSIONS: Dyslipoproteinemia is highly prevalent in patients with polyarticular juvenile idiopathic arthritis and is primarily related to decreased high-density lipoprotein cholesterol levels; therefore, early intervention is essential.

Marangoni, Roberta Goncalves; Hayata, Andre L.; Borba, Eduardo F.; Azevedo, Pedro M.; Bonfa, Eloisa; Goldenstein-Schainberg, Claudia

2011-01-01

158

PPAR is a very low-density lipoprotein sensor in macrophages  

Microsoft Academic Search

Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor . The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein

Ajay Chawla; Chih-Hao Lee; Yaacov Barak; Weimin He; John Rosenfeld; Debbie Liao; Jungyeob Han; Heonjoong Kang; Ronald M. Evans

2003-01-01

159

Isolation and Characterization of an Abnormal High Density Lipoprotein in Tangier Disease  

PubMed Central

The nature of the high density lipoproteins has been investigated in five patients homozygous for Tangier disease (familial high density lipoprotein deficiency). It has been established that Tangier high density lipoproteins, as isolated by ultracentrifugation, are morphologically heterogenous and contain several proteins (Apo B, albumin, and Apo A-II). An abnormal lipoprotein has been isolated from the d = 1.063-1.21 g/ml ultracentrifugal fraction by agarose-column chromatography which contains apoprotein A-II as the sole protein constituent. In negative-stain electron microscopy, these lipoproteins appeared as spherical particles 55-75 Å in diameter. By a variety of criteria (immunochemical, polyacrylamide electrophoresis, amino acid composition, and fluorescence measurements), apoprotein A-I the major apoprotein of normal high density lipoproteins and the C apoproteins were absent from this lipoprotein. As demonstrated by 125I very low density lipoprotein incubation experiments with Tangier plasma, C apoproteins did not associate with lipoproteins of d = 1.063-1.21 g/ml. Tangier apoprotein A-II, isolated to homogeneity by delipidation of the apoprotein A-II-containing lipoprotein or Sephadex G-200 guanidine-HCl chromatography of the d = 1.063-1.21 g/ml fraction, was indistinguishable from control apoprotein A-II with respect to amino acid composition and migration of tryptic peptides in urea-polyacrylamide electrophoresis. The ability of Tangier apoprotein A-II to bind phospholipid was demonstrated by in vitro reconstitution experiments and morphological and chemical analysis of lipid-protein complexes. It is concluded that normal high density lipoproteins, as defined by polypeptide composition and morphological appearance, are absent from Tangier plasma and that as a consequence, the impairment of C apoprotein metabolism contributes to the hypertriglyceridemia and fasting chylomicronemia observed in these patients. Images

Assmann, Gerd; Herbert, Peter N.; Fredrickson, Donald S.; Forte, Trudy

1977-01-01

160

Constitutive Androstane Receptor Activation Decreases Plasma Apolipoprotein B-Containing Lipoproteins and Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice  

PubMed Central

Objective The goal of this study was to determine the impact of the nuclear receptor constitutive androstane receptor (CAR) on lipoprotein metabolism and atherosclerosis in hyperlipidemic mice. Methods and Results Low-density lipoprotein receptor–deficient (Ldlr?/?) and apolipoprotein E–deficient (ApoE?/?) mice fed a Western-type diet were treated weekly with the Car agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or the vehicle only for 8 weeks. In Ldlr?/? mice, treatment with TCPOBOP induced a decrease in plasma triglyceride and intermediate-density lipoprotein/low-density lipoprotein cholesterol levels (?30% decrease in both cases after 2 months, P<0.01). These mice also showed a significant reduction in the production of very-low-density lipoproteins associated with a decrease in hepatic triglyceride content and the repression of several genes involved in lipogenesis. TCPOBOP treatment also induced a marked increase in the very-low-density lipoprotein receptor in the liver, which probably contributed to the decrease in intermediate-density lipoprotein/low-density lipoprotein levels. Atherosclerotic lesions in the aortic valves of TCPOBOP-treated Ldlr?/? mice were also reduced (?60%, P<0.001). In ApoE?/? mice, which lack the physiological apoE ligand for the very-low-density lipoprotein receptor, the effect of TCPOBOP on plasma cholesterol levels and the development of atherosclerotic lesions was markedly attenuated. Conclusion CAR is a potential target in the prevention and treatment of hypercholesterolemia and atherosclerosis.

Sberna, Anne-Laure; Assem, Mahfoud; Xiao, Rui; Ayers, Steve; Gautier, Thomas; Guiu, Boris; Deckert, Valerie; Chevriaux, Angelique; Grober, Jacques; Guern, Naig Le; Pais de Barros, Jean-Paul; Moore, David D.; Lagrost, Laurent; Masson, David

2014-01-01

161

Triolein and trilinolein ameliorate oxidized low-density lipoprotein-induced oxidative stress in endothelial cells.  

PubMed

Uptake of oxidized low-density lipoprotein by endothelial cells is a critical step for the initiation of atherosclerosis. Triacylglycerol uptake in these cells is understood to be a part of the process. The present investigation, comparison among the effects of simple acylglycerol, including tristearin, triolein, and trilinolein, upon oxidized low-density lipoprotein -induced oxidative stress was undertaken. Results indicated that trilinolein (78 % ± 0.02) and triolein (90 % ± 0.01) increased cell viability of endothelial cells exposed to oxidized low-density lipoprotein, whereas tristearin decreased the cell viability (55 % ± 0.03) (P < 0.05). Oxidized low-density lipoprotein treatment significantly increased apoptosis (23 %), compared to cells simultaneously exposed to trilinolein (19 %) or triolein (16 %), where apoptosis was reduced (P < 0.05). On the other hand, exposure to tristearin further increased oxidized low-density lipoprotein -induced cell apoptosis (34 %). Treatment with trilinolein or triolein on oxidized low-density lipoprotein -stimulated endothelial cells inhibited the expression of ICAM-1 and E-selectin mRNA. Moreover, both trilinolein and triolein demonstrated a strong antioxidant response to oxidative stress caused by oxidized low-density lipoprotein. Taken together, the results indicate trilinolein and triolein possess anti-inflammatory properties, which are mediated via the antioxidant defense system. PMID:24604600

Luo, Ting; Deng, Ze-Yuan; Li, Xiao-Ping; Rao, Huan; Fan, Ya-Wei

2014-05-01

162

Heterogeneity of human very low density lipoproteins by gel filtration chromatography  

Microsoft Academic Search

Very low density lipoproteins were separated by gel filtration on Sepharose 4B. A decrease in mean particle diameter and flotation rate was seen with increasing elution volumes. The smaller lipoproteins had relatively more protein and phospholipid and less triglyceride than the larger ones. No differences were noted in the relative contents of the various phospholipids or partial glycerides between small

Steven H. Quarfordt; Anne Nathans; Marie Dowdee; Helen L. Hilderman

2010-01-01

163

Aging affects high-density lipoprotein composition and function.  

PubMed

Most coronary deaths occur in patients older than 65years. Age associated alterations in the composition and function of high-density lipoproteins (HDL) may contribute to cardiovascular mortality. The effect of advanced age on the composition and function of HDL is not well understood. HDL was isolated from healthy young and elderly subjects. HDL composition, cellular cholesterol efflux/uptake, anti-oxidant properties and paraoxonase activity were assessed. We observed a 3-fold increase of the acute phase protein serum amyloid A, an increased content of complement C3 and proteins involved in endopeptidase/protease inhibition in HDL of elderly subjects, whereas levels of apolipoprotein E were significantly decreased. HDL from elderly subjects contained less cholesterol but increased sphingomyelin. Most importantly, HDL from elderly subjects showed defective antioxidant properties, lower paraoxonase 1 activity and was more rapidly taken up by macrophages, whereas cholesterol efflux capability was not altered. These findings suggest that aging alters HDL composition, resulting in functional impairment that may contribute to the onset/progression of cardiovascular disease. PMID:23792422

Holzer, Michael; Trieb, Markus; Konya, Viktoria; Wadsack, Christian; Heinemann, Akos; Marsche, Gunther

2013-09-01

164

Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.  

PubMed

Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavonoids negated the Cu(2+)-induced increase in electrophoretic mobility of LDL. Antioxidant activity of gnaphaliin and tiliroside was significantly different when diluted plasma was oxidised by adding 1 mM CuSO(4). Although both flavonoids again reduced the TBARS production, tiliroside showed higher activity than gnaphaliin (IC(50)=10.6+/-2.5 microM vs. IC(50)>50 microM). In conclusion, tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol. PMID:17084992

Schinella, Guillermo R; Tournier, Horacio A; Máñez, Salvador; de Buschiazzo, Perla M; Del Carmen Recio, María; Ríos, José Luis

2007-01-01

165

High-density lipoprotein exerts vasculoprotection via endothelial progenitor cells.  

PubMed

Endothelial progenitor cells (EPC) enhance endothelial cell repair, improve endothelial dysfunction and are a predictor for cardiovascular mortality. High-density lipoprotein (HDL) cholesterol levels inversely correlate with cardiovascular events and have vasculoprotective effects. Here we postulate that HDL influences EPC biology. HDL and EPC were isolated according to standard procedures. Differentiation of mononuclear cells into DiLDL/lectin positive cells was enhanced after HDL treatment compared to vehicle. HDL was able to inhibit apoptosis (TUNEL assay, annexin V staining) while proliferation (BrdU incorporation) of early outgrowth colonies after extended cell cultivation (14 days) was increased. Flow chamber experiments revealed an improved adhesion of HDL pre-incubated EPC on human coronary artery endothelial cells (HCAEC) compared to vehicle while HDL treatment of HCAEC prevented adhesion of inflammatory cells. Flow cytometry demonstrated an up-regulation of beta2- and alpha4-integrins on HDL pre-incubated EPC. Blocking experiments revealed a unique role of beta2-integrin in EPC adhesion. Treatment of wild-type mice with recombinant HDL after endothelial denudation resulted in enhanced re-endothelialization compared to vehicle. Finally, in patients with coronary artery disease a correlation between circulating EPC and HDL concentrations was demonstrated. We provide evidence that HDL mediates important vasculoprotective action via the improvement of function of circulating EPC. PMID:18705697

Petoumenos, Vasileios; Nickenig, Georg; Werner, Nikos

2009-01-01

166

Targeting high-density lipoproteins: update on a promising therapy.  

PubMed

Numerous epidemiological studies have demonstrated the atheroprotective roles of high density lipoproteins (HDL), so that HDL is established as an independent negative risk factor. The protective effect of HDL against atherosclerosis is mainly attributed to their capacity to bring peripheral excess cholesterol back to the liver for further elimination into the bile. In addition, HDL can exert other protective functions on the vascular wall, through their anti-inflammatory, antioxidant, antithrombotic and cytoprotective properties. HDL-targeted therapy is thus an innovative approach against cardiovascular risk and atherosclerosis. These pleiotropic atheroprotective properties of HDL have led experts to believe that "HDL-related therapies" represent the most promising next step in fighting against atherosclerosis. However, because of the heterogeneity of HDL functions, targeting HDL is not a simple task and HDL therapies that lower cardiovascular risk are NOT yet available. In this paper, an overview is presented about the therapeutic strategies currently under consideration to raise HDL levels and/or functions. Recently, clinical trials of drugs targeting HDL-C levels have disappointingly failed, suggesting that HDL functions through specific mechanisms should be targeted rather than increasing per se HDL levels. PMID:24074699

Verdier, Céline; Martinez, Laurent O; Ferrières, Jean; Elbaz, Meyer; Genoux, Annelise; Perret, Bertrand

2013-11-01

167

Cigarette smoke extract inhibits oxidative modification of low density lipoprotein.  

PubMed

Oxidative modification of low density lipoprotein (LDL) by cigarette smoke has been suggested in several recent studies. To characterize possible modification of LDL by cigarette smoke extract (CSE), we incubated LDL with CSE either in the presence or absence of the chemical pro-oxidants, cupric chloride or 2,2'-azo-bis(2-amidinopropane) hydrochloride (AAPH). Surprisingly, CSE inhibited oxidative modification of LDL induced by either copper or AAPH. Under such oxidant stress conditions, CSE inhibited formation of thiobarbituric acid-reactive substances and also inhibited the increased agarose gel electrophoretic mobility of LDL in a dose-response manner. In addition, CSE prevented degradation of phosphatidylcholine to lysophosphatidylcholine and also fragmentation of the apolipoprotein B-100 moiety of LDL. Finally, CSE inhibited loss of immunoreactivity of the treated LDL with a murine monoclonal antibody against human apolipoprotein B-100. On the other hand, at higher concentrations, CSE per se was still able to cause structural changes in LDL. After incubation with CSE for 24 h, LDL showed a slight increase in agarose gel electrophoretic mobility, a slight loss of immunoreactivity with monoclonal antibody, and a marked increase in protein carbonyl formation. Lipid peroxidation did not appear to be involved in the modification of LDL caused by CSE. It is suggested that reactive aldehydes present in cigarette smoke may cause direct chemical modification of LDL. Furthermore, the free radical-scavenging potential of the tar fraction of cigarette smoke may be responsible for the apparent antioxidant properties of CSE against LDL oxidation. PMID:7772077

Chen, C; Loo, G

1995-01-20

168

Carbon disulfide modification and impaired catabolism of low density lipoprotein.  

PubMed

Carbon disulfide interacts in vitro with low density lipoprotein (LDL), resulting in an increased electrophoretic mobility of the particle, due to a decrease in free amino groups of apolipoprotein B-100. The processing of carbon disulfide-modified LDL through the apo B/E receptor pathway of cultured human fibroblasts is decreased as compared to that of native LDL, depending on the level of modification. Carbon disulfide-modified LDL is recognized and degraded by the scavenger pathway of macrophages, but to a lesser extent than acetylated LDL. Carbon disulfide modification decreases the ability of the LDL to down-regulate sterol synthesis and to stimulate cholesterol esterification in fibroblasts. Carbon disulfide-modified LDL markedly stimulates cholesteryl ester formation in macrophages, albeit to a lesser extent than acetylated LDL. These results indicate that after carbon disulfide modification the LDL catabolism is shifted to the scavenger pathway, and are consistent with the fact that carbon disulfide intoxication accelerates the appearance of atherosclerotic lesions. PMID:2783203

Laurman, W; Salmon, S; Mazière, C; Mazière, J C; Auclair, M; Theron, L; Santus, R

1989-08-01

169

Serotonin increases macrophage uptake of oxidized low density lipoprotein.  

PubMed

Macrophage uptake of oxidized low density lipoprotein leads to cellular cholesterol accumulation and foam cell formation. Atherogenesis involves platelet activation with subsequent serotonin release. Incubation of J-774 A.1 murine macrophages as well as mouse peritoneal macrophages with serotonin for 2-18 hours at 37 degrees C, followed by cell wash and a further incubation of the cells for 18 hours in the presence of oxidized LDL (protein concentration 10-75 mg/l), resulted in up to 85% elevation in cellular uptake of the lipoprotein. Maximal effect was found after preincubation of the cells for 18 hours in the presence of 25 mumols/l serotonin. At lower or higher serotonin concentrations and with longer or shorter times of preincubation, cellular degradation of oxidized LDL was reduced. Under similar incubation conditions (with oxidized LDL), macrophage cholesterol accumulation was also increased by serotonin from 65 to 75 micrograms cholesterol per mg cell protein. This effect of serotonin was the result of a serotonin-mediated increase in the affinity of oxidized LDL towards its receptor without a significant change in the number of the receptors. Specific binding of serotonin to J-774 A.1 macrophages was demonstrated. Ten mumols/l of ketanserine (serotonin antagonist) completely blocked the stimulatory effect of serotonin on the cellular uptake of oxidized LDL. After injection of serotonin into the peritoneal cavity of thioglycolate-stimulated mice (250 nmol/mouse), the collected macrophages showed a 34% enhanced degradation of oxidized [125I]LDL compared with control cells collected from mice that were not injected with serotonin. Platelets from patients with carcinoid syndrome contained about twice as much serotonin as platelets from healthy subjects. Platelets were activated with collagen (1 mg/l) and platelet-conditioned medium was collected. Platelet-conditioned medium from healthy subjects enhanced the cellular uptake of oxidized LDL by 33%, whereas a similar concentration (protein concentration 15 mg/l) of platelet-conditioned medium from the patients increased macrophage uptake of oxidized LDL by 75%. Incubation of macrophages with platelet conditioned medium in the presence of ketanserine completely abolished the stimulation of oxidized LDL degradation, implying serotonin involvement in this process. We conclude that serotonin enhancement of oxidized LDL uptake by macrophages may be relevant in atherogenesis where both platelet activation and foam cell formation occur. PMID:1581411

Aviram, M; Fuhrman, B; Maor, I; Brook, G J

1992-02-01

170

Dietary fish protein modulates high density lipoprotein cholesterol and lipoprotein lipase activity in rabbits.  

PubMed

To explore the pathways by which fish protein feeding influences HDL metabolism, postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured in rabbits fed fish protein or soybean protein combined with corn oil or coconut oil in a 2 x 2 factorial arrangement. In addition to greater serum total and LDL-cholesterol concentrations, the elevated HDL cholesterol concentration caused by feeding fish protein, compared with soybean protein, was accompanied by lower VLDL triglycerides and parallel higher lipoprotein lipase activity in fish protein-fed rabbits. These results suggest an enhanced assembly of circulating HDL through promoted lipoprotein lipase activity in rabbits fed fish protein. Moreover, dietary proteins and lipids interacted with one another to alter HDL triglycerides and liver cholesterol concentrations. Diet-induced changes in lipoprotein lipase activity were, however, not related to insulinemia, which was unaltered by purified diet feeding. The present results suggest that fish protein may affect HDL metabolism through the modulation of lipoprotein lipase activity in rabbits. PMID:1640268

Bergeron, N; Deshaies, Y; Jacques, H

1992-08-01

171

Oxidized lipids in the diet are incorporated by the liver into very low density lipoprotein in rats  

Microsoft Academic Search

Previous studies have shown that the quantity of oxidized lipids in the diet directly correlates with the level of oxidized chylomicrons in mesenteric lymph and the level of oxidized lipids in endogenous lipoproteins such as very low density lipoprotein (VLDL) and low density lipoprotein (LDL). The aim of the present study was to determine whether oxidized fatty acids in the

Ilona Staprans; Joseph H. Rapp; Xian-Mang Pan; Kenneth R. Feingold

172

Racial differences in the distribution of a low density lipoprotein receptor-related protein (LRP) polymorphism and its association with serum lipoprotein, lipid and apolipoprotein levels  

Microsoft Academic Search

The low density lipoprotein (LDL) receptor-related protein (LRP) is a cell receptor that has close structural homology to the LDL and very low density lipoprotein receptors and thus is believed to play an important role in lipid metabolism. This study was carried out to evaluate the distribution of a known tetranucleotide repeat polymorphism in the LRP gene and its association

Meagan R Harris; Clareann H Bunker; Richard F Hamman; Dharambir K Sanghera; Christopher E Aston; M. Ilyas Kamboh

1998-01-01

173

The low-density lipoprotein receptor gene family: multiple roles in lipid metabolism  

Microsoft Academic Search

The low-density lipoprotein receptor gene family encompasses a class of endocytic receptors that exhibit structural similarities\\u000a to the low-density lipoprotein receptor. Members of this gene family are present in both vertebrate and nonvertebrate species.\\u000a The identification of naturally occurring mutations and the application of gene targeting to inactivate receptor genes enabled\\u000a us to develop animal models to investigate the consequences

Thomas E. Willnow

1999-01-01

174

Modulated serum activities and concentrations of paraoxonase in high density lipoprotein deficiency states  

Microsoft Academic Search

Paraoxonase is a high density lipoprotein (HDL) associated enzyme with a hypothesised role in the protection of low density lipoproteins (LDL) from oxidative stress. The present study examined paraoxonase in several genetically distinct HDL deficiency states. Despite reduction or even absence of detectable HDL, enzyme activity was present in sera from A-I-Pisa, A-I-Helsinki, A-I-Milano and Tangier patients. Both enzyme activities

Richard W James; Marie-Claude Blatter Garin; Laura Calabresi; Roberto Miccoli; Arnold von Eckardstein; Marju Tilly-Kiesi; Marja-Riitta Taskinen; Gerd Assmann; Guido Franceschini

1998-01-01

175

A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol  

Microsoft Academic Search

The accurate quantitation of high density lipo- proteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma frac- tion of d > 1.063 g\\/ml. A more practical approach is the specific precipitation of apolipoprotein B (apoB)-contain- ing lipoproteins by sulfated

G. Russell Warnick; John J. Albers

176

Measurement of low-density lipoprotein cholesterol in assessment and management of cardiovascular disease risk.  

PubMed

The deposition of cholesterol in the arterial wall by the infiltration of low-density lipoproteins (LDLs) is a key step in the development of atherosclerosis. In this Commentary, we discuss recent recommendations for clinical laboratory measurement of low-density lipoprotein cholesterol (LDL-C) and its utility both for assessing cardiovascular disease risk and as a tool in the management of patients receiving lipid-lowering therapy. PMID:24942398

Jialal, I; Remaley, A T

2014-07-01

177

Protective effect of dietary capsaicin on induced oxidation of low-density lipoprotein in rats  

Microsoft Academic Search

An animal study was carried out to examine the beneficial influence of the known hypocholesterolemic spice principle-capsaicin on the susceptibility of low-density lipoprotein to oxidation in normal and hypercholesterolemic condition. In rats rendered hypercholeterolemic by maintaining them on a cholesterol-enriched diet for eight weeks, inclusion of capsaicin (0.015%) in the diet, produced significant hypocholesterolemic effect. Oxidation of low-density lipoprotein was

R. K. Kempaiah; H. Manjunatha; K. Srinivasan

2005-01-01

178

Reconstituted High-Density Lipoprotein Modulates Activation of Human Leukocytes  

PubMed Central

An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL) has been demonstrated in atherosclerosis and in sepsis models. An increase of adhesion molecules as well as tissue factor expression on endothelial cells in response to inflammatory or danger signals are attenuated by the treatment with rHDL. Here we show the inhibitory effect of rHDL on the activation of human leukocytes in a whole blood assay as well as on monocyte-derived human dendritic cells (DC). Multiplex analysis of human whole blood showed that phytohaemagglutinin (PHA)-induced secretion of the cytokines IL-1?, IL-1RA, IL-2R, IL-6, IL-7, IL-12(p40), IL-15 and IFN-? was inhibited. Furthermore, an inhibitory effect on the production of the chemokines CCL-2, CCL-4, CCL-5, CXCL-9 and CXCL-10 was observed. Activation of granulocytes and CD14+ monocytes by PHA is inhibited dose-dependently by rHDL shown as decreased up-regulation of ICAM-1 surface expression. In addition, we found a strong inhibitory effect of rHDL on toll-like receptor 2 (TLR2)- and TLR4-mediated maturation of DC. Treatment of DC with rHDL prevented the up-regulation of cell surface molecules CD80, CD83 and CD86 and it inhibited the TLR-driven activation of inflammatory transcription factor NF-?B. These findings suggest that rHDL prevents activation of crucial cellular players of cellular immunity and could therefore be a useful reagent to impede inflammation as well as the link between innate and adaptive immunity.

Kropf, Alain; Miescher, Sylvia; Spycher, Martin O.; Rieben, Robert

2013-01-01

179

Oxidized low density lipoprotein and inflammation in gout patients.  

PubMed

To analyze the levels of oxidized low density lipoprotein (ox-LDL) and inflammatory cytokines in the plasma of gout patients. The levels of ox-LDL, hypersensitive C-reactive protein (hs-CRP), interleukin-1?, interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) were measured in the plasma of 41 gout patients [28 in acute phase episode, 13 in intermittent phase (IP)], and in 40 healthy controls. The relationship between ox-LDL and inflammation was also explored by measuring the levels of several pro-inflammatory cytokines in the plasma. The plasma levels of ox-LDL, hs-CRP, IL-6 and TNF-? were significantly increased in patients with gout in the acute phase compared to those in the IP group and healthy controls (P < 0.05), but the levels of TGF-? were significantly lower in the acute phase group than in the IP group and healthy controls (P < 0.01). The levels of ox-LDL in the gout patients in the IP were significantly higher than those in healthy controls (P < 0.05). Correlation analysis indicated that the levels of ox-LDL were positively correlated with hs-CRP, IL-6 and TNF-? (r = 0.343, r = 0.386, r = 0.659, P < 0.01, respectively), but negatively correlated with TGF-? levels in patients in the acute phase (r = -0.240, P < 0.05). The levels of ox-LDL in gout patients were significantly higher than those in healthy controls. The changes in ox-LDL levels may be associated with enhanced inflammation in gout patients. PMID:24068523

Jiang, Xingliang; Li, Min; Yang, Qibin; Du, Lijun; Du, Juan; Zhou, Jingguo

2014-05-01

180

Speciated Human High Density Lipoprotein Protein Proximity Profiles†  

PubMed Central

It is expected that the attendant structural heterogeneity of human high density lipoprotein (HDL) complexes is a determinant of its varied metabolic functions. To determine structural heterogeneity of HDL, major apolipoprotein stoichiometry profiles in human HDL were determined. First, HDL was separated into two main populations, with and without apolipoprotein (apo) A-II, LpA-I and LpA-I/A-II respectively. Each main population was further separated into six individual subfractions using size exclusion chromatography (SEC). Protein proximity profiles (PPP) of major apolipoproteins in each individual subfraction was determined by optimally cross-linking apolipoproteins within individual particles with bis(sulfosuccinimidyl)suberate (BS3), a bifunctional cross linker, followed by molecular weight determination by MALDI-MS. The PPPs of LpA-I subfractions indicated that the number of apoA-I molecules increased from two to three to four upon increase in the LpA-I particle size. On the other hand, the entire population of LpA-I/A-II demonstrated the presence of only two proximal apoA-I molecules per particle, while the number of apoA-II molecules varied from one dimeric apoA-II to two and then to three. For most of the above PPP profiles, an additional population that contained a single molecule of apoC-III in addition to apoA-I and/or apoA-II was detected. Upon composition analyses of individual subpopulations, LpA-I/A-II displayed comparable proportions for total protein (~58%), phospholipids (~21%) total cholesterol (~16%), triglycerides (~5%) and free cholesterol (~4%) across subfractions. LpA-I components, on the other hand, showed significant variability. This novel information on HDL subfractions will form a basis for better understanding particle specific functions of HDL.

Gauthamadasa, Kekulawalage; Rosales, Corina; Pownall, Henry J.; Macha, Stephen; Jerome, W. Gray; Huang, Rong; Silva, R. A.Gangani. D.

2010-01-01

181

PCSK9 gene mutations and low-density lipoprotein cholesterol.  

PubMed

Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a newly-identified circulating protein in cholesterol metabolism in mammals, including humans, which has emerged as a new pharmacological target for hypocholesterolemia. It has been demonstrated that PCSK9 gene mutations are associated with hyper- or hypocholesterolemia. In the latter case, the incidence of coronary heart disease (CHD) is markedly reduced, suggesting that low level of low-density lipoprotein cholesterol (LDL-C) at birth is highly beneficial. Loss-of-function PCSK9 mutations will result in lower LDL-C levels and protect against CHD. Conversely, patients harboring gain-of-function PCSK9 mutations will suffer from familial autosomal dominant hypercholesterolemia (ADH), a disease characterized by elevated LDL-C plasma concentration. Although compelling evidence has suggested that PCSK9 can impair the LDL receptor (LDLR) pathway, its biological role in cholesterol metabolism remains to be defined. According to data from previous studies, PCSK9 appears to be a promising therapeutic target due to its role as a major LDLR regulator. Specific pharmacological inhibitors of PCSK9 have demonstrated a significant impact on plasma LDL-C concentrations. Therefore, understanding the relationship between PCSK9 and its genetic variants, on one hand, and the level of plasma LDL-C, on the other hand, may be clinically useful due to the fact that this protein has become a key target of lipid-lowering therapy. In this manuscript we mainly review recent data with regard to the association between PCSK9 genetic variants and plasma LDL-C concentrations, and outline the clinical implications. PMID:24518357

Wu, Na-Qiong; Li, Jian-Jun

2014-04-20

182

Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis.  

PubMed

Atherosclerosis remains one of the most common causes of death in the United States and throughout the world because of the lack of early detection. Macrophage apoptosis is a major contributor to the instability of atherosclerotic lesions. Development of an apoptosis targeted high-density lipoprotein (HDL)-mimicking nanoparticle (NP) to carry contrast agents for early detection of vulnerable plaques and the initiation of preventative therapies that exploit the vascular protective effects of HDL can be attractive for atherosclerosis. Here, we report the construction of a synthetic, biodegradable HDL-NP platform for detection of vulnerable plaques by targeting the collapse of mitochondrial membrane potential that occurs during apoptosis. This HDL mimic contains a core of biodegradable poly(lactic-co-glycolic acid), cholesteryl oleate, and a phospholipid bilayer coat that is decorated with triphenylphosphonium (TPP) cations for detection of mitochondrial membrane potential collapse. The lipid layer provides the surface for adsorption of apolipoprotein (apo) A-I mimetic 4F peptide, and the core contains diagnostically active quantum dots (QDs) for optical imaging. In vitro uptake, detection of apoptosis, and cholesterol binding studies indicated promising detection ability and therapeutic potential of TPP-HDL-apoA-I-QD NPs. In vitro studies indicated the potential of these NPs in reverse cholesterol transport. In vivo biodistribution and pharmacokinetics indicated favorable tissue distribution, controlled pharmacokinetic parameters, and significant triglyceride reduction for i.v.-injected TPP-HDL-apoA-I-QD NPs in rats. These HDL NPs demonstrate excellent biocompatibility, stability, nontoxic, and nonimmunogenic properties, which prove to be promising for future translation in early plaque diagnosis and might find applications to prevent vulnerable plaque progression. PMID:23671083

Marrache, Sean; Dhar, Shanta

2013-06-01

183

Melatonin inhibits oxidative modification of human low-density lipoprotein.  

PubMed

An important property of melatonin is that it is a free-radical scavenger or antioxidant. Since free radicals can induce oxidative modification of low-density lipoprotein (LDL), a process believed to be involved in atherogenesis, we were prompted to evaluate the capacity of melatonin to prevent oxidative modification of LDL. To induce oxidation, human LDL (0.4 mg protein/ml) was incubated at 37 degrees C with either 10 microM cupric chloride or 10 mM 2,2'-azo-bis-(2-amidinopropane) dihydrochloride (AAPH) for 3 hr or 24 hr, respectively. Several assays were then performed to unequivocally determine the extent of LDL oxidation. Compared to native LDL, oxidized LDL had increased agarose gel electrophoretic mobility and weaker immunoreactivity with a murine monoclonal antibody to human apolipoprotein B-100. Measurement of thiobarbituric acid-reactive substances (TBARS) revealed that native LDL contained 1.8 +/- 0.6 nmoles TBARS/mg protein, whereas copper-oxidized LDL contained 53 +/- 4 nmoles TBARS/mg protein. However, when present during incubation, melatonin (0.125-4 mM) inhibited in a concentration-dependent manner the increase in electrophoretic mobility, decrease in immunoreactivity of LDL, and increase in formation of TBARS caused by either copper or AAPH. In a fourth assay, phospholipid analysis of LDL was performed. Native LDL contained 420 +/- 9 nmoles phosphatidylcholine (PC)/mg LDL protein and 30 +/- 20 nmoles lysophosphatidylcholine (LysPC)/mg LDL protein. LDL incubated with copper had a decreased PC content (276 +/- 48 nmoles PC/mg LDL protein) and increased LysPC content (76 +/- 22 nmoles LysPC/mg LDL protein). But when present during the incubation of LDL with copper, melatonin attenuated in a concentration-dependent manner the degradation of PC to LysPC. Therefore, we conclude that melatonin can inhibit oxidative modification of LDL in vitro. PMID:9247205

Kelly, M R; Loo, G

1997-05-01

184

Role of Lipids in Spheroidal High Density Lipoproteins  

PubMed Central

We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly.

Vuorela, Timo; Catte, Andrea; Niemela, Perttu S.; Hall, Anette; Hyvonen, Marja T.; Marrink, Siewert-Jan; Karttunen, Mikko; Vattulainen, Ilpo

2010-01-01

185

Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity.  

PubMed

The aim of the present study was to investigate the high-density lipoprotein (HDL) structural characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol [HDL-C], 92 +/- 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 +/- 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL2/HDL3 ratio. HALP profile A was characterized in 28 patients by increased HDL2/HDL3 ratio, HDL2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL2/HDL3 ratio within the normal range and by the increase of all HDL subclasses (HDL(2b,2a,3a,3b,3c)), LpA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL2/HDL3 ratio, HDL2b, and LpA-I levels associated with decreased HL activity. PMID:9711993

Sich, D; Saïdi, Y; Giral, P; Lagrost, L; Egloff, M; Auer, C; Gautier, V; Turpin, G; Beucler, I

1998-08-01

186

LDL and HDL subclass distribution in patients with end-stage renal diseases  

Microsoft Academic Search

Objectives: To examine the alterations in LDL and HDL subclass distribution in ESRD patients compared with a control group and to investigate the relationship of LDL particle size to the other plasma lipoproteins levels.Design and methods: Plasma lipids, LDL and HDL subclasses were determined in 63 hemodialysis patients (HD), 42 predialysis patients and 345 control subjects. Lipoprotein subclasses were separated

Sonja B Alabakovska; Bojana B Todorova; Danica D Labudovic; Katerina N Tosheska

2002-01-01

187

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia  

Microsoft Academic Search

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol ?4.14 mmol\\/L (160 mg\\/dl) and

Michael Davidson; Patrick Ma; Evan A Stein; Antonio M Gotto; Ali Raza; Rohini Chitra; Howard Hutchinson

2002-01-01

188

Macrophage receptors responsible for distinct recognition of low density lipoprotein containing pyrrole or pyridinium adducts: models of oxidized low density lipoprotein  

Microsoft Academic Search

Oxidation of low density lipoproteins (LDL) in- duced by incubation with Cu 2 1 ions results in the formation of a heterogeneous group of aldehydic adducts on lysyl resi- dues (Lys) of apolipoprotein B (apoB) that are thought to be responsible for the uptake of oxidized LDL (oxLDL) by macrophages. To define the structural and chemical criteria governing such cell

Eugene A. Podrez; George Hoppe; June O'Neil; Lawrence M. Sayre; Nader Sheibani; Henry F. Hoff

189

Comparison of gemfibrozil versus simvastatin in familial combined hyperlipidemia and effects on apolipoprotein-B-containing lipoproteins, low-density lipoprotein subfraction profile, and low-density lipoprotein oxidizability  

Microsoft Academic Search

We evaluated in a double-blind, placebo-controlled, randomized trial of 45 well-defined patients with familial combined hyperlipidemia, the effect of gemfibrozil (1, 200 mg\\/day) or simvastatin (20 mg\\/day) on apolipoprotein-B (apo-B)-containing lipoproteins, low-density lipoprotein (LDL) subfraction profile, and LDL oxidizability. Although both drugs reduced plasma cholesterol and triglyceride concentrations, gemfibrozil reduced plasma triglycerides more effectively and simvastatin reduced plasma cholesterol more

Sebastian J. H. Bredie; Tjerk W. A. de Bruin; Pierre N. M. Demacker; John J. P. Kastelein; Anton F. H. Stalenhoef

1995-01-01

190

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

PubMed

Many of the published data on the lipid profile of athletes is based on studies of endurance athletes. The data on soccer players are rare. The purpose of this study was to examine serum high-density lipoprotein cholesterol subfractions and lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31 well-trained male collegiate soccer players were divided into 2 groups: 16 defenders and 15 offenders. They were compared with 16 sedentary controls. Dietary information was obtained with a food frequency questionnaire. The subjects were all non-smokers and were not taking any drug known to affect the lipid and lipoprotein metabolism. The offenders had significantly higher high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and apolipoprotein A-I than the defenders and controls, whereas the defenders had the significantly higher high-density lipoprotein2 cholesterol than the controls. Both groups of athletes had significantly higher lecithin:cholesterol acyltransferase activity than the controls. The results indicate that favorable lipid and lipoprotein profile could be obtained by vigorous soccer training. PMID:23152129

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

2013-05-01

191

Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.  

PubMed

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients. PMID:9920146

Saïdi, Y; Sich, D; Camproux, A; Egloff, M; Federspiel, M C; Gautier, V; Raisonnier, A; Turpin, G; Beucler, I

1999-01-01

192

Lipoprotein lipase- and hepatic triglyceride lipase- promoted very low density lipoprotein degradation proceeds via an apolipoprotein E-dependent mechanism.  

PubMed

Apolipoprotein E (apoE) is the primary recognition signal on triglyceride-rich lipoproteins responsible for interacting with low density lipoprotein (LDL) receptors and LDL receptor-related protein (LRP). It has been shown that lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) promote receptor-mediated uptake and degradation of very low density lipoproteins (VLDL) and remnant particles, possibly by directly binding to lipoprotein receptors. In this study we have investigated the requirement for apoE in lipase-stimulated VLDL degradation. We compared binding and degradation of normal and apoE-depleted human VLDL and apoE knockout mouse VLDL in human foreskin fibroblasts. Surface binding at 37 degrees C of apoE knockout VLDL was greater than that of normal VLDL by 3- and 40-fold, respectively, in the presence of LPL and HTGL. In spite of the greater stimulation of surface binding, lipase-stimulated degradation of apoE knockout mouse VLDL was significantly lower than that of normal VLDL (30, 30, and 80%, respectively, for control, LPL, and HTGL treatments). In the presence of LPL and HTGL, surface binding of apoE-depleted human VLDL was, respectively, 40 and 200% of normal VLDL whereas degradation was, respectively, 25 and 50% of normal VLDL. LPL and HTGL stimulated degradation of normal VLDL in a dose-dependent manner and by a LDL receptor-mediated pathway. Maximum stimulation (4-fold) was seen in the presence LPL (1 microgram/ml) or HTGL (3 microgram/ml) in lovastatin-treated cells. On the other hand, degradation of apoE-depleted VLDL was not significantly increased by the presence of lipases even in lovastatin-treated cells. Surface binding of apoE-depleted VLDL to metabolically inactive cells at 4 degrees C was higher in control and HTGL-treated cells, but unchanged in the presence of LPL. Degradation of prebound apoE-depleted VLDL was only 35% as efficient as that of normal VLDL. Surface binding of apoE knockout or apoE-depleted VLDL was to heparin sulfate proteoglycans because it was completely abolished by heparinase treatment. However, apoE appears to be a primary determinant for receptor-mediated VLDL degradation. Our studies suggest that overexpression of LPL or HTGL may not protect against lipoprotein accumulation seen in apoE deficiency. PMID:11060356

Medh, J D; Fry, G L; Bowen, S L; Ruben, S; Wong, H; Chappell, D A

2000-11-01

193

Computational Lipidology: Predicting Lipoprotein Density Profiles in Human Blood Plasma  

Microsoft Academic Search

Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond “bad” and “good” cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood

Katrin Hübner; Thomas Schwager; Karl Winkler; Jens-Georg Reich; Hermann-Georg Holzhütter

2008-01-01

194

Development of Capture Assays for Different Modifications of Human Low-Density Lipoprotein  

PubMed Central

Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL), copper-oxidized LDL (oxLDL), N?(carboxymethyl) lysine (CML)-modified LDL, and advanced glycosylation end product (AGE)-modified LDL were obtained by immunization of rabbits with in vitro-modified human LDL preparations. After absorption of apolipoprotein B (ApoB) antibodies, we obtained antibodies specific for each modified lipoprotein with unique patterns of reactivity. MDA-LDL antibodies reacted strongly with MDA-LDL and also with oxLDL. CML-LDL antibodies reacted strongly with CML-LDL and also AGE-LDL. oxLDL antibodies reacted with oxLDL but not with MDA-LDL, and AGE-LDL antibodies reacted with AGE-LDL but not with CML-LDL. Capture assays were set with each antiserum, and we tested their ability to capture ApoB-containing lipoproteins isolated from precipitated immune complexes (IC) and from the supernatants remaining after IC precipitation (free lipoproteins). All antibodies captured lipoproteins contained in IC more effectively than free lipoproteins. Analysis of lipoproteins in IC by gas chromatography-mass spectrometry showed that they contained MDA-LDL and CML-LDL in significantly higher concentrations than free lipoproteins. A significant correlation (r = 0.706, P < 0.019) was obtained between the MDA concentrations determined by chemical analysis and by the capture assay of lipoproteins present in IC. In conclusion, we have developed capture assays for different LDL modifications in human ApoB/E lipoprotein-rich fractions isolated from precipitated IC. This approach obviates the interference of IC in previously reported modified LDL assays and allows determination of the degree of modification of LDL with greater accuracy.

Virella, Gabriel; Derrick, M. Brooks; Pate, Virginia; Chassereau, Charlyne; Thorpe, Suzanne R.; Lopes-Virella, Maria F.

2005-01-01

195

Urinary Neopterin and Microalbuminuria in Patients Treated by Low-density Lipoprotein Apheresis  

Microsoft Academic Search

Low-density lipoprotein (LDL)-apheresis is a method of extracorporeal elimination of LDL-cholesterol in patients with severe primary lipoprotein disorders. LDL-cholesterol activates macrophages, which play an impor- tant role in atheromatous plaque formation. In the present study, we have investigated urinary neopterin, a spe- cific marker of macrophage activation and microalbuminuria, an indicator of generalized vascular dysfunction, after a single LDL-apheresis procedure

Melanie Cermanová; Bohuslav Melichar; Dagmar Solichová; Milan Bláha; Vladimír Bláha; Martin Blazek; Jaroslav Cerman Jr; Zdenek Zadák

196

Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants  

Microsoft Academic Search

Human serum paraoxonase (PON1) can protect low density lipoprotein (LDL) from oxidation induced by either copper ion or by the free radical generator azo bis amidinopropane hydrochloride (AAPH). During LDL oxidation in both of these systems, a time-dependent inactivation of PON arylesterase activity was observed. Oxidized LDL (Ox-LDL) produced by lipoprotein incubation with either copper ion or with AAPH, indeed

Michael Aviram; Mira Rosenblat; Scott Billecke; John Erogul; Robert Sorenson; Charles L Bisgaier; Roger S Newton; Bert La Du

1999-01-01

197

Ath1, a Gene Determining Atherosclerosis Susceptibility and High Density Lipoprotein Levels in Mice  

Microsoft Academic Search

High density lipoprotein (HDL) is the major plasma lipoprotein found in mice fed normal laboratory chow containing 4% fat. When female mice from some inbred strains, such as C57BL\\/6, are fed a high fat diet (1.25% cholesterol, 15% fat, and 0.5% cholic acid), the levels of HDL-cholesterol decrease by about 50%, and lipid staining lesions form in the aorta within

Beverly Paigen; Diane Mitchell; Karen Reue; Arlene Morrow; Aldons J. Lusis; Renee C. Leboeuf

1987-01-01

198

Induction of Macrophage Antitumor Activity by Acetylated Low Density Lipoprotein Containing Lipophilic Muramyl Tripeptide  

Microsoft Academic Search

A method has been developed for the selective delivery of lipophilic immunomodulators to macrophages, which results in the induction of antitumor activity. This method utilizes exhaustively acetylated low density lipoprotein (acetyl-LDL) to deliver the lipophilic immunomodulator, muramyl tripeptide phosphatidylethanolamine (MTP-PtdEtn; amide composed of N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-alanine and dipalmitoyl phosphatidylethanolamine) to macrophages (Mphi ) by means of a scavenger lipoprotein receptor pathway. The

J. Michael Shaw; William S. Futch; Lawrence B. Schook

1988-01-01

199

Degradation of Cationized Low Density Lipoprotein and Regulation of Cholesterol Metabolism in Homozygous Familial Hypercholesterolemia Fibroblasts  

Microsoft Academic Search

Cultured fibroblasts derived from patients with homozygous familial hypercholesterolemia, which lack functional low density lipoprotein (LDL) receptors, fail to bind, take up, or degrade the lipoprotein with high affinity; therefore LDL-cholesterol is not made available for suppression of cholesterol synthesis or activation of cholesteryl ester formation. When LDL was given a positive charge by reaction with N,N-dimethyl-1,3-propanediamine (cationized LDL), the

Sandip K. Basu; Joseph L. Goldstein; Richard G. W. Anderson; Michael S. Brown

1976-01-01

200

ApoE4 trapping by the low density lipoprotein receptor  

Microsoft Academic Search

Low density lipoprotein receptor (LDLr) is critical for plasma lipoprotein clearance and a decreased LDLr expression has been thought to explain the increased plasma cholesterol and atherosclerosis risk in humans with apolipoprotein (apo) E4. However, in mice expressing human apoE4 instead of their mouse counterpart, increased LDLr expression caused accumulation of cholesterol-rich apoE-poor chylomicron remnants, and resulted in significant atherosclerosis.

Michael K. Altenburg; Sudi I. Malloy; Chris Knouff; John S. Parks; Nobuyo Maeda

2004-01-01

201

Low Density Lipoprotein Receptor-Related Protein (LRP) Expression Varies among Hep G2 Cell Lines  

Microsoft Academic Search

The multiligand receptor, low density lipoprotein receptor-related protein (LRP), is implicated in processes such as atherosclerosis and fibrinolysis through its mediation of the catabolism of lipoproteins, proteases, and protease inhibitor complexes. The hepatoma cell line Hep G2 expresses LRP and has been used widely to investigate the catabolism of LRP ligands including tissue-type plasminogen activator (tPA). However, the mechanism and

Philip G Grimsley; Kathryn A Quinn; Colin N Chesterman; Dwain A Owensby

1997-01-01

202

Softness of Atherogenic Lipoproteins: A Comparison of Very Low Density Lipoprotein (VLDL) and Low Density Lipoprotein (LDL) Using Elastic Incoherent Neutron Scattering (EINS)  

PubMed Central

Apolipoprotein B100 (apoB100)-containing plasma lipoproteins (LDL and VLDL) supply tissues and cells with cholesterol and fat. During lipolytic conversion from VLDL to LDL the size and chemical composition of the particles change, but the apoB100 molecule remains bound to the lipids and regulates the receptor mediated uptake. The molecular physical parameters which control lipoprotein remodeling and enable particle stabilization by apoB100 are largely unknown. Here, we have compared the molecular dynamics and elasticities of VLDL and LDL derived by elastic neutron scattering temperature scans. We have determined thermal motions, dynamical transitions, and molecular fluctuations, which reflect the temperature-dependent motional coupling between lipid and protein. Our results revealed that lipoprotein particles are extremely soft and flexible. We found substantial differences in the molecular resiliences of lipoproteins, especially at higher temperatures. These discrepancies not only can be explained in terms of lipid composition and mobility but also suggest that apoB100 displays different dynamics dependent on the lipoprotein it is bound to. Hence, we suppose that the inherent conformational flexibility of apoB100 permits particle stabilization upon lipid exchange, whereas the dynamic coupling between protein and lipids might be a key determinant for lipoprotein conversion and atherogenicity.

Mikl, Christian; Peters, Judith; Trapp, Marcus; Kornmueller, Karin; Schneider, Wolfgang J.; Prassl, Ruth

2011-01-01

203

Softness of atherogenic lipoproteins: a comparison of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) using elastic incoherent neutron scattering (EINS).  

PubMed

Apolipoprotein B100 (apoB100)-containing plasma lipoproteins (LDL and VLDL) supply tissues and cells with cholesterol and fat. During lipolytic conversion from VLDL to LDL the size and chemical composition of the particles change, but the apoB100 molecule remains bound to the lipids and regulates the receptor mediated uptake. The molecular physical parameters which control lipoprotein remodeling and enable particle stabilization by apoB100 are largely unknown. Here, we have compared the molecular dynamics and elasticities of VLDL and LDL derived by elastic neutron scattering temperature scans. We have determined thermal motions, dynamical transitions, and molecular fluctuations, which reflect the temperature-dependent motional coupling between lipid and protein. Our results revealed that lipoprotein particles are extremely soft and flexible. We found substantial differences in the molecular resiliences of lipoproteins, especially at higher temperatures. These discrepancies not only can be explained in terms of lipid composition and mobility but also suggest that apoB100 displays different dynamics dependent on the lipoprotein it is bound to. Hence, we suppose that the inherent conformational flexibility of apoB100 permits particle stabilization upon lipid exchange, whereas the dynamic coupling between protein and lipids might be a key determinant for lipoprotein conversion and atherogenicity. PMID:21790144

Mikl, Christian; Peters, Judith; Trapp, Marcus; Kornmueller, Karin; Schneider, Wolfgang J; Prassl, Ruth

2011-08-31

204

Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue  

PubMed Central

Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a 13C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial 13C-triglyceride and 13C-NEFA over 6 h compared with controls. AUC6 h of plasma 13C-triglyceride and 13C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in 13C-triolein oxidation rate, which suggests lower 13C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT 3H-lipid following a 4 h incubation of women's WAT with synthetic 3H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower 3H-TRL hydrolysis and 3H-NEFA storage. Treatment of women's WAT with their own LDL decreased 3H-TRL hydrolysis and 3H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated 3H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo.

Bissonnette, Simon; Salem, Huda; Wassef, Hanny; Saint-Pierre, Nathalie; Tardif, Annie; Baass, Alexis; Dufour, Robert; Faraj, May

2013-01-01

205

Increased oxidizability of plasma low density lipoprotein from patients with coronary artery disease.  

PubMed

Oxidative modification of lipoproteins may play a crucial role in the pathogenesis of atherosclerosis. This study was designed to examine whether increased lipid peroxides and/or oxidative susceptibility of plasma lipoproteins occur in patients with coronary artery disease. The levels of lipid peroxides, estimated as thiobarbituric acid-reactive substances (TBARS), were significantly greater in the plasma and very low density lipoprotein (VLDL) of symptomatic patients with coronary artery disease than in those of healthy persons, but the TBARS levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) showed insignificant difference between patients and normals. To evaluate the oxidative susceptibility of lipoproteins, we employed in vitro Cu2+ oxidation of lipoproteins monitored by changes in fluorescence, TBARS level, trinitrobenzene sulfonic acid (TNBS) reactivity, apolipoprotein immunoreactivity and agarose gel electrophoretic mobility. While pooled VLDL and LDL of normal controls were oxidized at 5-10 microM Cu2+, pooled VLDL and LDL of patients with coronary artery disease were oxidized at 1-2.5 microM Cu2+, i.e., at relatively lower oxidative stress. At 5 microM Cu2+, VLDL and LDL of patients with coronary artery disease still showed a faster oxidation rate, judged by the rate of fluorescence increase, higher TBARS level, less TNBS reactivity, greater change in apo B immunoreactivity and higher electrophoretic mobility than those of normal controls. However, the difference on the oxidizability of HDL was insignificant for patients vs. normals. In conclusion, we have shown that plasma VLDL and LDL of patients with coronary artery disease are more susceptible to in vitro oxidative modification than those of healthy persons. The data suggest that enhanced oxidizability of plasma lipoproteins may be an important factor influencing the development of coronary artery disease. PMID:8280789

Chiu, H C; Jeng, J R; Shieh, S M

1994-01-11

206

Nonresponsiveness of serum high-density lipoprotein-cholesterol to high dose ascorbic acid administration in normal men.  

PubMed

In a prospective, single-blind, 12-wk study, serum lipids were measured serially in nine normal male volunteers before and during oral administration of megadose ascorbic acid (1 g vitamin C/day). Study results revealed no significant effect of vitamin therapy on serum cholesterol, high-density lipoprotein-cholesterol, triglycerides, or calculated low-density lipoprotein-cholesterol. Megadose ascorbic acid therapy is not effective in elevating serum high-density lipoprotein-cholesterol in normal adult men. PMID:7293936

Johnson, G E; Obenshain, S S

1981-10-01

207

Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism  

Microsoft Academic Search

Relative to saturated fatty acids, trans -fatty acids\\/ hydrogenated fat-enriched diets have been reported to in- crease low density lipoprotein (LDL) cholesterol levels and either decrease or have no effect on high density lipopro- tein (HDL) cholesterol levels. To better understand the ef- fect of trans -fatty acids\\/hydrogenated fat on HDL choles- terol levels and metabolism, 36 subjects (female, n

A. H. Lichtenstein; M. Jauhiainen; S. McGladdery; L. M. Ausman; S. M. Jalbert; M. Vilella-Bach; C. Ehnholm; J. Frohlich; E. J. Schaefer

208

Composition and Distribution of Low Density Lipoprotein Fractions in Hyperapobetalipoproteinemia, Normolipidemia, and Familial Hypercholesterolemia  

Microsoft Academic Search

Hyperapobetalipoproteinemia is defined as the combination of a normal low density lipoprotein (LDL) cholesterol in the face of an increased LDL apolipoprotein B (apoB) protein. To examine the physical basis for the apparent disproportion between LDL cholesterol and apoB characteristic of this syndrome, we used density gradient ultracentrifugation to isolate LDL fractions from 10 normal subjects, from 20 patients with

B. Teng; G. R. Thompson; A. D. Sniderman; T. M. Forte; R. M. Krauss; P. O. Kwiterovich

1983-01-01

209

Cardiovascular Events With Increased Lipoprotein-Associated Phospholipase A2 and Low High-Density Lipoprotein-Cholesterol The Veterans Affairs HDL Intervention Trial  

Microsoft Academic Search

Objective—Lipoprotein-associated phospholipase A2 (Lp-PLA2), a proinflammatory enzyme that predominantly circulates with low-density lipoprotein (LDL), has been shown in general populations to predict cardiovascular (CV) events. We sought to determine whether increased Lp-PLA2 would also predict CV events in the absence of high LDL-cholesterol (LDL-C), in a population with low high-density lipoprotein-cholesterol (HDL-C). Methods and Results—Plasma Lp-PLA2 activity was measured at

Sander J. Robins; Dorothea Collins; Jeanenne J. Nelson; Hanna E. Bloomfield; Bela F. Asztalos

210

Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia  

Microsoft Academic Search

Diabetic dyslipoproteinemia characterized by hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and often elevated low-density lipoprotein (LDL) cholesterol with predominance of small, dense LDL is a strong risk factor for atherosclerosis. It is unclear whether fibrate or statin therapy is more effective in these patients. We compared atorvastatin (10 mg\\/day) with fenofibrate (200 mg\\/day), each for 6 weeks separated by a

Robert J. A Frost; Carsten Otto; H. Christian Geiss; Peter Schwandt; Klaus G Parhofer

2001-01-01

211

Atorvastatin treatment beneficially alters the lipoprotein profile and increases low-density lipoprotein particle diameter in patients with combined dyslipidemia and impaired fasting glucose\\/type 2 diabetes  

Microsoft Academic Search

Diabetic dyslipidemia is featured by hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol levels, and elevated low-density lipoprotein (LDL) cholesterol commonly in the form of small, dense LDL particles. First-line treatment, fibrates versus statins or both, of dyslipidemia in diabetic patients has been the focus of debate. We investigated the potential hypolipidemic effects of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor

Louisa Pontrelli; Wendy Parris; Khosrow Adeli; Raphael C. Cheung

2002-01-01

212

Detection of autoantibodies against oxidized low-density lipoproteins and of IgG-bound low density lipoproteins in patients with coronary artery disease  

Microsoft Academic Search

The role of oxidized low-density lipoprotein (ox-LDL) in the pathogenesis of atherosclerosis has been the object of intense investigation. It has been proposed that, due to the antigenic properties of ox-LDL, the anti-ox-LDL antibody titre could represent a useful index of in vivo LDL oxidation. On the other hand, LDL immune complexes (LDL-IC) have been demonstrated in patients with coronary

Agnés Boullier; Martial Hamon; Evelyne Walters-Laporte; Françoise Martin-Nizart; Régine Mackereel; Jean-Charles Fruchart; Michel Bertrand; Patrick Duriez

1995-01-01

213

High-density lipoprotein cholesterol as an independent risk factor in cardiovascular disease: assessing the data from framingham to the veterans affairs high-density lipoprotein intervention trial  

Microsoft Academic Search

The Framingham Heart Study found that high-density lipoprotein cholesterol (HDL-C) was the most potent lipid predictor of coronary artery disease risk in men and women >49 years of age. The Air Force\\/Texas Coronary Atherosclerosis Prevention Study (AFCAPS\\/TexCAPS), in which subjects were randomized to treatment with lovastatin or placebo, also reported a striking benefit of treatment, particularly in patients with HDL-C

William E Boden

2000-01-01

214

Inclusion of calcium during isolation of high-density lipoprotein from plasma maintains antioxidant function.  

PubMed

We investigated how inclusion of calcium during isolation of high-density lipoprotein (HDL) affected its antioxidant function. Following isolation, HDL was dialyzed against 0.154M NaCl without or with added calcium (1mM). HDL's paraoxonase 1 activity was unaffected by calcium treatment (87±11% of normal vs. 89±16% of normal, P=0.826). In contrast, whereas HDL dialyzed with calcium inhibited oxidation of low-density lipoprotein (LDL) by 87±10%, HDL dialyzed without calcium inhibited oxidation by only 58±19% (P=0.004). Thus, inclusion of calcium during isolation is important for maintaining HDL's antioxidant function. PMID:24657818

Lynch, Sean M; Lorenz, Joseph; Klotz, Steven

2014-06-01

215

Raising low levels of high-density lipoprotein cholesterol is an important target of therapy.  

PubMed

Recent clinical trials in patients with coronary heart disease indicate, for the very first time, that increasing low levels of high-density lipoprotein (HDL) cholesterol significantly reduces the cumulative occurrence of cardiovascular and cerebrovascular events in patients whose only lipid abnormality was low HDL with normal levels of low-density lipoprotein (LDL) cholesterol and triglycerides. These data provide a compelling scientific basis for a more targeted and segmental approach to managing patients with dyslipidemia, where decreasing elevated levels of LDL cholesterol and increasing low levels of HDL cholesterol should comprise dual targets of pharmacotherapy. PMID:11078282

Boden, W E; Pearson, T A

2000-03-01

216

Divergent approaches to the treatment of dyslipidemia with low levels of high-density lipoprotein cholesterol.  

PubMed

Further therapy should be considered for patients who have reached target low-density lipoprotein cholesterol (LDL-C) levels but have low plasma levels of high-density lipoprotein cholesterol (HDL-C) since rates of coronary artery disease continue to be high for a sizable proportion of this population. Lifestyle approaches include dietary changes, smoking cessation, moderate alcohol intake, concomitant drug reassessment, and specific coexistent conditions. Aggressive statin therapy still leaves a high residual rate of cardiac events. Other drug approaches include estrogen, fibrate, niacin therapy, and combinations of these agents. Recent results from an ongoing trial of combination extended-release prescription niacin plus lovastatin are very promising. PMID:11374858

Pearson, T A

2000-12-21

217

Isolation of very low density lipoprotein phospholipids enriched in ethanolamine phospholipids from rats injected with Triton WR 1339  

Microsoft Academic Search

Phospholipids carried by very low density lipoprotein (VLDL) are hydrolysed in circulation by lipoprotein and hepatic lipases and lecithin-cholesterol acyltransferase. We have previously demonstrated [6] [J.J. Ågren, A. Ravandi, A. Kuksis, G. Steiner, Structural and compositional changes in very low density lipoprotein triacylglycerols during basal lipolysis, Eur. J. Biochem. 269 (2002) 6223–6232] that the infusion of Triton WR 1339 (TWR),

Jyrki J. Ågren; Juha-Pekka Kurvinen; Arnis Kuksis

2005-01-01

218

Surface properties of native human plasma lipoproteins and lipoprotein models.  

PubMed

Plasma lipoprotein surface properties are important but poorly understood determinants of lipoprotein catabolism. To elucidate the relation between surface properties and surface reactivity, the physical properties of surface monolayers of native lipoproteins and lipoprotein models were investigated by fluorescent probes of surface lipid fluidity, surface lateral diffusion, and interfacial polarity, and by their reactivity to Naja melanoleuca phospholipase A2 (PLA2). Native lipoproteins were human very low, low-, and subclass 3 high-density lipoproteins (VLDL, LDL, and HDL3); models were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or its ether analog in single-bilayer vesicles, large and small microemulsions of POPC and triolein, and reassembled HDL (apolipoprotein A-I plus phospholipid). Among lipoproteins, surface lipid fluidity increased in the order HDL3 < LDL < VLDL, varying inversely with their (protein + cholesterol)/phospholipid ratios. Models resembled VLDL in fluidity. Both lateral mobility in the surface monolayer and polarity of the interfacial region were lower in native lipoproteins than in models. Among native lipoproteins and models, increased fluidity in the surface monolayer was associated with increased reactivity to PLA2. Addition of cholesterol (up to 20 mol%) to models had little effect on PLA2 activity, whereas the addition of apolipoprotein C-III stimulated it. Single-bilayer vesicles, phospholipid-triolein microemulsions, and VLDL have surface monolayers that are quantitatively similar, and distinct from those of LDL and HDL3. Surface property and enzymatic reactivity differences between lipoproteins and models were associated with differences in surface monolayer protein and cholesterol contents. Thus differences in the surface properties that regulate lipolytic reactivity are a predictable function of surface composition. PMID:9533698

Massey, J B; Pownall, H J

1998-02-01

219

Overexpression of Human Hepatic Lipase and ApoE in Transgenic Rabbits Attenuates Response to Dietary Cholesterol and Alters Lipoprotein Subclass Distributions  

Microsoft Academic Search

The effect of the expression of human hepatic lipase (HL) or human apoE on plasma lipoproteins in transgenic rabbits in response to dietary cholesterol was compared with the response of nontransgenic control rabbits. Supplementation of a chow diet with 0.3% cholesterol and 3.0% soybean oil for 10 weeks resulted in markedly increased levels of plasma cholesterol and VLDL and IDL

Carlo M. Barbagallo; Jianglin Fan; Patricia J. Blanche; Manfredi Rizzo; John M. Taylor; Ronald M. Krauss

2010-01-01

220

Raising high-density lipoprotein cholesterol with niacin and fibrates: a comparative review.  

PubMed

A growing number of trials that used fibrates and niacin alone or in combination with other lipid-altering agents have shown that both these drugs are effective for reducing total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and for increasing high-density lipoprotein cholesterol (HDL-C) levels. These lipid changes are associated with a reduction in events such as fatal and nonfatal myocardial infarction, stroke, and transient ischemic attack. In angiographic trials, they are associated with disease regression, increased minimal luminal diameter, and protection from risk of new lesions. In a head-to-head comparison study, niacin 2,000 mg/day increased HDL-C more than gemfibrozil 1,200 mg/day, and decreased the total cholesterol-to-HDL-C ratio, lipoprotein (a) (Lp[a]), and fibrinogen levels significantly more. Combination therapies of niacin plus a resin or statin are effective, well tolerated, and safe. PMID:11374856

Sprecher, D L

2000-12-21

221

Fish oil supplementation reduces beta-very low density lipoprotein in type III dysbetalipoproteinemia.  

PubMed

beta-Very low density lipoproteins (beta-VLDLs) are atherogenic, cholesterol-rich chylomicron and VLDL remnants that accumulate in the plasma of type III dysbetalipoproteinemic subjects. To evaluate the effect of fish oil supplementation on plasma beta-VLDL concentrations, we compared the lipid and lipoprotein responses in nine type III and nine type IV hyperlipidemic subjects. Each individual received 6 g/day omega-3 fatty acids for 12 weeks. Before treatment, the mean total cholesterol, total triglyceride, VLDL triglyceride, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol levels were not different between groups. Conversely, VLDL cholesterol, intermediate density lipoprotein (IDL) cholesterol, and IDL triglycerides were higher in type III than in type IV subjects. Fish oil supplementation was associated with significantly lower levels of cholesterol (-50%), triglycerides (-50%), and apolipoprotein B (-50%) in the d less than 1.006 g/ml ultracentrifugation plasma fraction in both groups, compatible with a reduction in VLDL in type III and type IV subjects, and in beta-VLDL in type III subjects. This finding was confirmed by analysis of the plasma zonal ultracentrifugation profile and the agarose gel electrophoretic pattern of lipoproteins, which showed a reduction in but not a disappearance of remnant particles, suggesting that not all beta-VLDL had been cleared after treatment. The levels of IDL cholesterol and IDL triglycerides (1.006 less than d less than 1.019 g/ml) were not affected in either group. Initially low LDL cholesterol (1.019 less than d less than 1.063 g/ml) and HDL cholesterol levels rose significantly in both groups. In type III hyperlipidemics, all LDL cholesterol values remained below 120 mg/dl, whereas they were higher than 150 mg/dl after treatment in two individuals with type IV hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2065040

Dallongeville, J; Boulet, L; Davignon, J; Lussier-Cacan, S

1991-01-01

222

Ultrastructural and physiological evidence for corticosteroid-induced alterations in hepatic production of very low density lipoprotein particles  

Microsoft Academic Search

The cause of corticosteroid-induced hyperlipoprotein- emia was studied in rats and mice. An ultrastructural morpho- metric method was utilized to demonstrate alterations in hepato- cyte very low density lipoprotein content, and Triton WR 1339-treated rats were used to identify changes in the removal of very low density lipoproteins from plasma. The results show that corticosteroid treatment results in (1) an

Eve P. Reaven; Orville G. Kolterman; Gerald M. Reaven

223

Lipoprotein profile and high-density lipoproteins: subfractions distribution in centenarians.  

PubMed

In order to assess the role of HDL on longevity, we studied HDL subfraction distribution in centenarian women compared with a group of weight- and gender-matched healthy normolipidemic controls. We did not find any significant difference in the mean plasma lipid, apolipoprotein, and Lp(a) levels. On the contrary, in spite of similar HDL-cholesterol concentrations (1.32 +/- 0.41 mmol/l in centenarians vs. 1.32 +/- 0.25 mmol/l in controls, p = not significant), HDL2b and HDL3a levels were, respectively, significantly increased and significantly reduced in centenarians in comparison with controls (HDL2b 32.4 +/- 9.2% in centenarians vs. 23.4 +/- 7.7% in controls, p < 0.002, and HDL3a 26.3 +/- 9.8% in centenarians vs. 34.1 +/- 7.3% in controls, p < 0.01). Moreover, HDL2b levels were significantly raised and HDL3a levels were significantly reduced in centenarians in comparison with both 'middle-aged' and 'elderly' subjects, whereas no difference for any HDL subfraction was found between the two groups of controls of different ages. Age was significantly correlated with HDL2b and HDL3a (respectively, +0.452, p < 0.001, and -0.370, p < 0.01) in all subjects, but not with all the other lipid, lipoprotein and apolipoprotein parameters, but we observed a large overlapping of individual values of HDL2b between centenarians and controls. Since HDL2b levels were found to be inversely correlated with coronary heart disease risk, we could speculate that, in some cases, this may probably favor a healthy ageing, but long-term longitudinal studies are necessary to define the relative importance of HDL subfractions distribution as a marker of longevity. Probably other factors or clinical characteristics play a major role in the ageing process. PMID:9523222

Barbagallo, C M; Averna, M R; Fradà, G; Noto, D; Cavera, G; Notarbartolo, A

1998-01-01

224

Calcium-channel blockers inhibit human low-density lipoprotein oxidation by oxygen radicals  

Microsoft Academic Search

Previous studies have shown that calcium channel blockers may reduce the development of experimental athero-sclerosis, and that nifedipine may slow the progression of coronary atherosclerosis in humans. The mechanisms responsible for this antiatherogenic effect are still unclear. It has been recently proposed that oxygen free radicals can induce the oxidation of human low-density lipoproteins (LDL) and that oxidized LDL may

Claudio Napoli; Massimo Chiariello; Giuseppe Palumbo; Giuseppe Ambrosio

1996-01-01

225

Regulation of guinea pig very low density lipoprotein secretion rates by dietary fat saturation  

Microsoft Academic Search

We investigated the effects of dietary fat saturation on very low density lipoprotein (VLDL) production in guinea pigs fed semipurified diets containing 15% (w\\/w) fat, either corn oil (GO, 58% linoleic acid), lard (LA, 42% oleic and 24% palmitic acids) or palm kernel oil (PK, 52% lauric and 18% myristic acids) for 4 weeks. Animals were given an intravenous injection

Ghada Abdel-Fattah; Maria Luz Fernandez; Donald J. McNamara

226

Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size  

Microsoft Academic Search

The fasting atherogenic dyslipidemia of visceral obesity, which includes the presence of small, dense low-density lipoprotein (LDL) particles, is predictive of an increased risk of coronary heart disease (CHD). It has also been suggested that progression of atherosclerosis may be accelerated in the presence of postprandial hyperlipidemia independently from the fasting dyslipidemic state. Studies have shown that the best predictor

Patricia Blackburn; Mélanie Côté; Charles Couillard; Agnès Pascot; Angelo Tremblay; Jean Bergeron; Isabelle Lemieux; Jean-Pierre Després

2003-01-01

227

Lipoxygenase-mediated transformation of human low density lipoprotein to an oxidized and cytotoxic complex1  

Microsoft Academic Search

We have been studying the mechanisms involved in the oxidative modification of low density lipoprotein (LDL) that lead to its transformation to a cytotoxic complex. Here we ex- amine the direct effect of soybean lipoxygenase (SLO), a 15- lipoxygenase, on normal human LDL. SLO oxidized LDL and rendered it cytotoxic; agents known to interfere with lipox- ygenase activity inhibited this

Martha K. Cathcart; Amy K. McNally; Guy M. Chisolmt

228

Comparative Effects of Copper, Iron, Vanadium and Titanium on Low Density Lipoprotein Oxidation in vitro  

Microsoft Academic Search

Introduction: Oxidation of low density lipoprotein (LDL) has been strongly implicated in the phathogenesis of atherosclerosis. The use of oxidants in dietary food stuff may lead to the production of oxidized LDL and may increase both the development and the progression of atherosclerosis. The present work investigated the effects of some elements including: copper (Cu), iron (Fe), vanadium (V) and

Mohsen Ani; Ali Asghar Moshtaghie; Hassan Ahmadvand

2007-01-01

229

Comparison of gradient gel electrophoresis and zonal ultracentrifugation for quantitation of high density lipoproteins  

Microsoft Academic Search

The study was conducted to compare gradient gel electrophoresis (GGE) and zonal ultracentrifugation for quanti- tation of human plasma high density lipoproteins (HDL). Plasma samples were obtained from seven normal subjects consuming a high fat diet (65% total calories) followed by a high carbohydrate diet (65% total calories). HDL were fractionated into HDL2 and HDLS by zonal ultracentrifugation and lipid

Constance A. McNerney; Moti L. Kashyap; Roger L. Barnhart

230

Effects of Lycopene on the Susceptibility of Low-Density Lipoproteins to Oxidative Modification  

Microsoft Academic Search

The intake of antioxidants intake has been reported to be inversely associated with the incidence of coronary artery disease. To clarify the possible role of lipophilic antioxidants in prevention of atherosclerosis, we investigated the effects of lycopene on the susceptibility of low-density lipoprotein (LDL) to oxidative modification. In this study, \\

Mohammad Reza Safari

2007-01-01

231

High-density lipoproteins: an emerging target in the prevention of cardiovascular disease  

Microsoft Academic Search

High-density lipoproteins (HDLs) have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target

Belinda A Cutri; Neil J Hime; Stephen J Nicholls

2006-01-01

232

Achieving and maintaining national cholesterol education program low-density lipoprotein cholesterol goals with five statins  

Microsoft Academic Search

PurposeMost patients fail to achieve and maintain low-density lipoprotein (LDL) cholesterol goals established by the National Cholesterol Education Program (NCEP). The Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS) was a randomized study comparing the efficacy and safety of five statins and their ability reduce LDL cholesterol to the NCEP target level.

Thomas C Andrews; Christie M Ballantyne; Judith A Hsia; Jeffrey H Kramer

2001-01-01

233

Autoantibodies against modified low-density lipoproteins in coronary artery disease  

Microsoft Academic Search

Objectives: To evaluate the importance of different autoantibodies against modified low-density lipoprotein (LDL) in patients with coronary artery disease (CAD). Background: Previous studies of autoantibodies against LDL have shown that patients with CAD have increased titers of autoantibodies against LDL modified by copper and malondialdehyde (MDA), whereas there is a lack of information about autoantibody titers against LDL modified by

Per Tornvall; Georg Waeg; Jan Nilsson; Anders Hamsten; Jan Regnström

2003-01-01

234

Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents  

Microsoft Academic Search

Oxidation of low density lipoproteins maybe a factor in the development of atherosclerosis. The Mediterranean diet rich in vegetables, grains, legumes, fruits, and oils, mainly olive oil, has been suggested to reduce the incidence of coronary heart disease, because of its low saturated and high monounsaturated fatty acids content. It is also possible that the natural antioxidants in the oil

Francesco Visioli; Giorgio Bellomo; GianFranco Montedoro; Claudio Galli

1995-01-01

235

Transfer of low density lipoprotein into the arterial wall and risk of atherosclerosis  

Microsoft Academic Search

The aim of the review is to summarize the present knowledge on determinants of transfer of low density lipoprotein (LDL) into the arterial wall, particularly in relation to the risk of development of atherosclerosis. The flux of LDL into the arterial wall (in moles of LDL per surface area per unit of time) has two major determinants, i.e. the LDL

Lars Bo Nielsen

1996-01-01

236

High-density Lipoprotein Cholesterol, Cognitive Function and Mortality in a U.S. National Cohort  

Microsoft Academic Search

Low levels of both high density lipoprotein cholesterol (HDL) and cognitive function are associated with increased mortality risk. HDL plays an important role in brain metabolism. We test the hypotheses that the relative protective effect of high HDL level as related to mortality is greater in persons with impaired cognitive function than in others. Data were analyzed from a longitudinal

Richard F Gillum; Thomas O Obisesan

2011-01-01

237

The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro  

Microsoft Academic Search

Oxidation of low density lipoprotein (LDL) is implicated in the development of atherosclerosis and dietary antioxidants may provide a useful therapy in the prevention of LDL oxidation and atheroma development. The aim of these experiments was to investigate the antioxidant activity of the soybean isoflavone, genistein, in in vitro models of LDL oxidation. Genistein inhibited copper-mediated oxidation of LDL in

Nicole Kerry; Mavis Abbey

1998-01-01

238

Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia  

Microsoft Academic Search

Patients with homozygous familial hypercholesterolemia (FH), as a result of the increased levels and prolonged residence time of low density lipoprotein (LDL) in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall, causing premature atherosclerosis. This phenomenon may enhance per se the physiological degradation of both protein and lipid component of LDL, which be more susceptible

Claudio Napoli; Alfredo Postiglione; Massimo Triggiani; Gaetano Corso; Giuseppe Palumbo; Virginia Carbone; Antonio Ruocco; Giuseppe Ambrosio; Silvana Montefusco; Antonio Malorni; Mario Condorelli; Massimo Chiariello

1995-01-01

239

Marked Reduction of High Density Lipoprotein Cholesterol in Mice Genetically Modified to Lack Apolipoprotein AI  

Microsoft Academic Search

Atherosclerosis is a major cause of morbidity and mortality in developed countries. In humans the risk of atherosclerosis is inversely correlated with plasma levels of high density lipoprotein (HDL). As a step in determining whether the experimental reduction of plasma HDL level will increase susceptibility to atherosclerosis, we have used gene targeting in embryonic stem cells to produce mice lacking

Roger Williamson; Denise Lee; John Hagaman; Nobuyo Maeda

1992-01-01

240

Effect of Low-Density Lipoprotein Apheresis on Circulating Endothelial Progenitor Cells in Familial Hypercholesterolemia  

Microsoft Academic Search

Background: Long-term treatment with low-density lipoprotein (LDL) apheresis (LA) has been shown to reduce the incidence of cardiovascular events in patients affected by familial hypercholesterolemia (FH). Data from experimental studies suggest that circulating endothelial progenitor cells (EPCs) can repair the vascular lesions caused by atherosclerosis. Since a reduction of these cells has been demonstrated to predict atherosclerosis progression, the aim

Alfonso Ramunni; Paola Brescia; Porzia Dambra; Laura Capuzzimati; Roberto Ria; Giacoma De Tullio; Francesco Resta; Gianpaolo Russi; Angelo Vacca; Pasquale Coratelli

2010-01-01

241

Comparison of apolipoprotein B to cholesterol in low density lipoproteins of patients with coronary heart disease  

Microsoft Academic Search

This study was carried out to determine whether patients with coronary heart disease (CHD) have an unusually high level of apolipoprotein B (apoB) relative to cholesterol (C) in low density lipoproteins (LDL). Seven groups of men were studied. Seventy-two with normolipidemia (NLP) had CHD doc- umented on clinical grounds; another 34 NLP patients had proven coronary artery disease (CAD) by

Gloria Lena Vega; Scott M. Grundy

242

Tobacco smoking, estrogen receptor   gene variation and small low density lipoprotein level  

Microsoft Academic Search

High levels of small low density lipoprotein (LDL) particles are a major risk factor for cardiovascular morbidity and mortality. Both estrogens and smoking, with known anti-estrogenic effects, alter the atherogenic lipid pro- file. We tested for a role of interaction between smoking and estrogen receptor a gene (ESR1) variation in association with plasma concentration of atherogenic small LDL particles and

Amanda M. Shearman; Serkalem Demissie; L. Adrienne Cupples; Inga Peter; Christopher H. Schmid; Jose M. Ordovas; Michael E. Mendelsohn; David E. Housman

2005-01-01

243

Inhibitory effect of tea flavonoids on the ability of cells to oxidize low density lipoprotein  

Microsoft Academic Search

Dietary flavonoid intake has been reported to be inversely related to mortality from coronary heart disease, and the anti-atherosclerotic effect of flavonoids is considered to be due probably to their antioxidant properties. Oxidation of low density lipoprotein (LDL) has been reported to be induced by the constituent cells of the arterial wall. Accordingly, we examined the effect of pretreatment with

Hiroshi Yoshida; Toshitsugu Ishikawa; Hiroshi Hosoai; Michio Suzukawa; Makoto Ayaori; Tetsuya Hisada; Shojiro Sawada; Atsushi Yonemura; Kenji Higashi; Toshimitsu Ito; Kei Nakajima; Takeshi Yamashita; Koji Tomiyasu; Masato Nishiwaki; Fumitaka Ohsuzu; Haruo Nakamura

1999-01-01

244

In vitro incorporation of radiolabeled cholesteryl esters into high and low density lipoproteins  

SciTech Connect

We have developed and validated a method for in vitro incorporation of radiolabeled cholesteryl esters into low density (LDL) and high density lipoproteins (HDL). Radiolabeled cholesteryl esters dissolved in absolute ethanol were mixed with LDL or HDL in the presence of lipoprotein-deficient serum (LPDS) as a source of core lipid transfer activity. The efficiency of incorporation was dependent on: (a) the core lipid transfer activity and quantity of LPDS, (b) the mass of added radiolabeled cholesteryl esters, (c) the length of incubation, and (d) the amount of acceptor lipoprotein cholesterol. The tracer incorporation was documented by repeat density gradient ultracentrifugation, agarose gel electrophoresis, and precipitation with heparin-MnCl2. The radiolabeling conditions did not affect the following properties of the lipoproteins: (1) chemical composition, (2) electrophoretic mobility on agarose gels, (3) hydrated density, (4) distribution of apoproteins on SDS gels, (5) plasma clearance rates, and (6) immunoprecipitability of HDL apoproteins A-I and A-II. Rat HDL containing radiolabeled cholesteryl esters incorporated in vitro had plasma disappearance rates identical to HDL radiolabeled in vivo.

Terpstra, A.H.; Nicolosi, R.J.; Herbert, P.N. (Brown Univ. Program in Medicine, Providence, RI (USA))

1989-11-01

245

Study of abnormal plasma low-density lipoprotein in rhesus monkeys with diet-induced hyperlipidemia  

Microsoft Academic Search

Male rhesus monkeys were divided into three groups: five were fed a regular primate chow diet and were used as controls; four received an ''average'' American diet; and five a special low-fat primate chow diet supplemented with 25 percent coconut oil and 2 percent cholesterol. In all of these animals, the plasma low-density lipoproteins (LDL) were isolated by ultracentrifugal flotation

Gunther M. Fless; Robert W. Wissler; Angelo M. Scanu

1976-01-01

246

Patients with early rheumatoid arthritis exhibit elevated autoantibody titers against mildly oxidized low-density lipoprotein and exhibit decreased activity of the lipoprotein-associated phospholipase A2  

Microsoft Academic Search

Rheumatoid arthritis is a chronic inflammatory disease, associated with an excess of cardiovascular morbidity and mortality due to accelerated atherosclerosis. Oxidized low-density lipoprotein (oxLDL), the antibodies against oxLDL and the lipoprotein-associated phospholipase A2 (Lp-PLA2) may play important roles in inflammation and atherosclerosis. We investigated the plasma levels of oxLDL and Lp-PLA2 activity as well as the autoantibody titers against mildly

Evangelia S Lourida; Athanasios N Georgiadis; Eleni C Papavasiliou; Athanasios I Papathanasiou; Alexandros A Drosos; Alexandros D Tselepis

2007-01-01

247

Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia  

NASA Astrophysics Data System (ADS)

Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

1993-04-01

248

Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein  

PubMed Central

The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed.

Sato, Koichi; Okajima, Fumikazu

2010-01-01

249

Multiple forms of sheep serum A-esterase activity associated with the high-density lipoprotein.  

PubMed Central

Five lipoproteins of sheep serum expressing A-esterase activity, but with differing activities towards four organophosphate substrates, were separated by a combination of gel filtration and ion-exchange chromatography. Each had an Mr of approx. 360,000 and contained a major peptide of Mr 28,000-30,000 that appeared to be present as several isoforms on urea/agarose isoelectric focusing. In every case this peptide split into a number of bands on urea/agarose isoelectric focusing. The bands appear to represent isoforms of the peptide, and four lipoproteins yielded characteristic patterns of bands. This peptide resembles the apolipoprotein A-I of human serum, and available evidence suggests that this is the protein that expresses A-esterase activity. Evidence is presented for the existence of different species of high-density lipoprotein HDL2 particles containing different complements of peptide isoforms and expressing contrasting substrate specificities towards organophosphates. Images Fig. 5.

Mackness, M I; Walker, C H

1988-01-01

250

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

PubMed

The increasing number of patients with metabolic syndrome is a critical global problem. In this study, we describe a novel geometrical electrophoretic separation method using a bioformulated-fiber matrix to analyze high-density lipoprotein (HDL) particles. HDL particles are generally considered to be a beneficial component of the cholesterol fraction. Conventional electrophoresis is widely used but is not necessarily suitable for analyzing HDL particles. Furthermore, a higher HDL density is generally believed to correlate with a smaller particle size. Here, we use a novel geometrical separation technique incorporating recently developed nanotechnology (Nata de Coco) to contradict this belief. A dyslipidemia patient given a 1-month treatment of fenofibrate showed an inverse relationship between HDL density and size. Direct microscopic observation and morphological observation of fractionated HDL particles confirmed a lack of relationship between particle density and size. This new technique may improve diagnostic accuracy and medical treatment for lipid related diseases. PMID:21171600

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

2011-02-01

251

Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein  

SciTech Connect

Cultures of human skin fibroblasts were labeled to high cholesterol specific activity with (/sup 3/H)cholesterol and incubated briefly (1-3 min) with normal human plasma. The plasma was fractionated by two-dimensional agarose-polyacrylamide gel electrophoresis and the early appearance of cholesterol label among plasma lipoproteins determined. A major part of the label at 1-min incubation was in a pre-beta-migrating apo A-I lipoprotein fraction with a molecular weight of ca. 70,000. Label was enriched about 30-fold in this fraction relative to its content of apo A-I (1-2% of total apo A-I). The proportion of label in this lipoprotein was strongly correlated with its concentration in plasma. Further incubation (2 min) in the presence of unlabeled cells demonstrated transfer of label from this fraction to a higher molecular weight pre-beta apo A-I species, to low-density lipoprotein, and to the alpha-migrating apo A-I that made up the bulk (96%) of total apo A-I in plasma. The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma.

Castro, G.R.; Fielding, C.J.

1988-01-12

252

Effect of Thyroid Dysfunction on High-Density Lipoprotein Subfraction Metabolism: Roles of Hepatic Lipase and Cholesteryl Ester Transfer Protein  

Microsoft Academic Search

To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apo- lipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL (namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)) in 18 hyperthyroid and 17 hypothyroid patients before and after treatment.

K. C. B. TAN; S. W. M. SHIU; A. W. C. KUNG

2010-01-01

253

Effects of sex on formation and properties of plasma very low density lipoprotein in vivo  

Microsoft Academic Search

The concentration and composition of the very low density lipoprotein (VLDL) lipids and the behavior of the VLDL in a density\\u000a gradient in the zonal ultracentrifuge were examined in plasma obtained from normal fed male and female rats before and after\\u000a intravenous injection of Triton WR-1339. Concentration of lipids in plasma VLDL of female rats was about half that of

Carlos Soler-Argilaga; Abraham Danon; Henry G. Wilcox; Murray Heimberg

1976-01-01

254

Intact human ceruloplasmin oxidatively modifies low density lipoprotein.  

PubMed Central

Ceruloplasmin is a plasma protein that carries most of the copper found in the blood. Although its elevation after inflammation and trauma has led to its classification as an acute phase protein, its physiological role is uncertain. A frequently reported activity of ceruloplasmin is its ability to suppress oxidation of lipids. In light of the intense recent interest in the oxidation of plasma LDL, we investigated the effects of ceruloplasmin on the oxidation of this lipoprotein. In contrast to our expectations, highly purified, undegraded human ceruloplasmin enhanced rather than suppressed copper ion-mediated oxidation of LDL. Ceruloplasmin increased the oxidative modification of LDL as measured by thiobarbituric acid-reacting substances by at least 25-fold in 20 h, and increased electrophoretic mobility, conjugated dienes, and total lipid peroxides. In contrast, ceruloplasmin that was degraded to a complex containing 115- and 19-kD fragments inhibited cupric ion oxidation of LDL, as did commercial preparations, which were also degraded. However, the antioxidant capability of degraded ceruloplasmin in this system was similar to that of other proteins, including albumin. The copper in ceruloplasmin responsible for oxidant activity was not removed by ultrafiltration, indicating a tight association. Treatment of ceruloplasmin with Chelex-100 removed one of seven copper atoms per molecule and completely blocked oxidant activity. Restoration of the copper to ceruloplasmin also restored oxidant activity. These data indicate that ceruloplasmin, depending on the integrity of its structure and its bound copper, can exert a potent oxidant rather than antioxidant action on LDL. Our results invite speculation that ceruloplasmin may be in part responsible for oxidation of LDL in blood or in the arterial wall and may thus have a physiological role that is quite distinct from what is commonly believed. Images

Ehrenwald, E; Chisolm, G M; Fox, P L

1994-01-01

255

Low and high density lipoprotein--cholesterol and coronary atherothrombosis.  

PubMed

After reviewing the general characteristics of lipids (LDL-C, VLDL-C, HDL-C) and atherothrombosis, including the I-VIII degrees of its histopathological arterial lesions (with contributions of J. E. Edwards and R. Virmani), the authors described the P. Libby's data on lipoprotein-associated phospholipaseA2 (Lp-PLA2) and its two inflammatory mediators: lysophosphatidylcholine and oxidized nonesterified fatty acids. They are involved in plaque progression and vulnerability. Lp-PLA2 is an emerging proinflammatory marker. The new drug darapladib inhibits Lp-PLA2 and acts against inflammation. LDL-C is present in the atherosclerotic plaque from the circulating blood in arterial lumen (through the dysfunctional endothelium) and vasa vasorum as well as after the decomposition of foam cells (monocytes-phagocytes, smooth muscle and dendritic cells) and outpoured erythrocytes (its membranes) after hemorrhage. The blood from the arterial lumen can also enter the atherosclerotic plaque through the lesions in its fibrous cap (erosion, fissure, rupture). Atherosclerosis as a disease or as an inevitable accompaniment of aging ("the senescence hypothesis"). The familial hypercholesterolemia is usually due to mutation of just one gene--a defective LDL-C receptor gene on chromosome 19. The accelerated and severe atherosclerosis very resistant to therapy occurs. The patients with homozygous familial hypercholesterolemia can die of myocardial infarction in early childhood. Therapeutic decrease of LDL-C and increase of HDL-C slows down the evolution of atherosclerosis, stabilizes the atherosclerotic plaques, and even brings about their partial regression. Statins, niacin, ezetimibe, LDL-C apheresis, and surgery: shunt between the portal and inferior caval veins, liver transplantation, and partial ileal bypass. The elevated LDL-C is the most established risk factor for atherosclerosis with impact on coronary heart disease mortality of 26%, and it should be the primary target of preventive and therapeutic efforts. PMID:19702110

Kanjuh, Vladimir; Ostoji?, Miodrag; Lali?, Nebojsa; Stoki?, Edita; Adi?-Cemerli?, Nada; Gojkovi?-Bukarica, Ljiljana

2009-01-01

256

The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B  

Microsoft Academic Search

To better define the role of environmental factors on LDL phenotypic expression, the authors determined LDL patterns in patients with acquired immunodeficiency syndrome (AIDS), and infection characterized by hypertriglyceridemia and weight loss. Similar to previous studies, plasma triglyceride levels were increased, whereas plasma cholesterol, LDL cholesterol, and HDL cholesterol levels were decreased in the AIDS subjects compared to those in

K. R. Feingold; R. M. Krauss; M. Pang; W. Doerrler; P. Jensen; C. Grunfeld

1993-01-01

257

Low density lipoprotein fraction assay for cardiac disease risk  

DOEpatents

A variable rate density gradient electrophoric gel is described which separate LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described.

Krauss, Ronald M. (Berkeley, CA); Blanche, Patricia J. (Berkeley, CA); Orr, Joseph (San Pablo, CA)

1999-01-01

258

A study of the use of polyethylene glycol in estimating cholesterol in high-density lipoprotein.  

PubMed

We studied polyethylene glycol 6000 precipitation of lipoproteins other than high-density lipoproteins, before cholesterol is estimated in the supernate. Other lipoproteins in the supernatant fractions were detected by using rocket immunoelectrophoresis. A polyethylene glycol concentration of 75 g/L in the final mixture appeared to be optimal, and results agreed with those obtained by ultracentrifugation. Differences in serum pH, use of polyethylene glycol from different suppliers, or the presence of ethylenediaminetetraacetate resulted in values that differed significantly (by 40 to 60 mumol/L) from the reference values. Polyethylene glycol did not interfere in four different methods for determination of cholesterol. In combination with an enzymic cholesterol method, the polyethylene glycol method appeared to be very precise, even when lipemic sera (triglycerides up to 5.5 mmol/L) were analyzed that had diminished high-density lipoprotein cholesterol values. We consider this method a method of choice, especially when lipemic sera are tested and enzymic cholesterol analysis is used. PMID:7438421

Demacker, P N; Hijmans, A G; Vos-Janssen, H E; van't Laar, A; Jansen, A P

1980-12-01

259

Apolipoprotein E on Hepatitis C Virion Facilitates Infection through Interaction with Low Density Lipoprotein Receptor  

PubMed Central

Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV associates with host apolipoproteins and enters hepatocytes through complex processes involving some combination of CD81, claudin-I, occludin, and scavenger receptor BI. Here we show that infectious HCV resembles very low density lipoprotein (VLDL) and that entry involves co-receptor function of the low density lipoprotein receptor (LDL-R). Blocking experiments demonstrate that ?-VLDL itself or anti-apolipoprotein E (apoE) antibody can block HCV entry. Knockdown of the LDL-R by treatment with 25-hydroxycholesterol or siRNA ablated ligand uptake and reduced HCV infection of cells, whereas infection was rescued upon cell ectopic LDL-R expression. Analyses of gradient-fractionated HCV demonstrate that apoE is associated with HCV virions exhibiting peak infectivity and dependence upon the LDL-R for cell entry. Our results define the LDL-R as a cooperative HCV co-receptor that supports viral entry and infectivity through interaction with apoE ligand present in an infectious HCV/lipoprotein complex comprising the virion. Disruption of HCV/LDL-R interactions by altering lipoprotein metabolism may therefore represent a focus for future therapy.

Owen, David M.; Huang, Hua; Ye, Jin; Gale, Michael

2009-01-01

260

Sweet potato (Ipomoea batatas L.) leaves suppressed oxidation of low density lipoprotein (LDL) in vitro and in human subjects  

PubMed Central

Sweet potato (Ipomoea batatas L.) leaves are consumed as vegetables around the world, especially in Southeast Asia. The aim of this study was to investigate the inhibitory effect of sweet potato leaves on low-density lipoprotein oxidation in vitro and in human subjects. We compared the antioxidant activity of 8 kinds of sweet potato leaves. Every sweet potato leaf had high radical scavenging activity and prolonged a lag time for starting low-density lipoprotein oxidation in vitro. We found that sweet potato leaves contained abundant polyphenol compounds and the radical scavenging activity and prolongation rate of lag time were highly correlated with total polyphenol content. We also confirmed that thiobarbituric acid reactive substances production was increased in endothelial cell-mediated low-density lipoprotein oxidation, which was decreased by treatment with sweet potato leaves. We further measured the low-density lipoprotein oxidizability in 13 healthy volunteers after their intake of 18 g of “Suioh”, raw sweet potato leaves. “Suioh” prolonged a lag time for starting low-density lipoprotein oxidation and decreased low-density lipoprotein mobility. These results suggest that sweet potato leaves have antioxidant activity leading to the suppression of low-density lipoprotein oxidation.

Nagai, Miu; Tani, Mariko; Kishimoto, Yoshimi; Iizuka, Maki; Saita, Emi; Toyozaki, Miku; Kamiya, Tomoyasu; Ikeguchi, Motoya; Kondo, Kazuo

2011-01-01

261

Low and High Density Lipoproteins and Chylomicrons as Regulators of Rate of Cholesterol Synthesis in Rat Liver in vivo  

Microsoft Academic Search

The steady-state levels of plasma cholesterol carried in high and low density lipoproteins and in chylomicrons were varied over a wide range by use of a constant-infusion technique. After 40 hr, the rates of hepatic cholesterol synthesis and levels of hepatic cholesterol esters were measured and were related to the plasma level of each of the lipoprotein fractions. From the

John M. Andersen; Stephen D. Turley; John M. Dietschy

1979-01-01

262

Characterization of the low-density-lipoprotein-receptor-independent interaction of beta-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro.  

PubMed Central

beta-Migrating very-low-density lipoprotein (beta-VLDL) is a cholesteryl-ester-enriched lipoprotein which under normal conditions is rapidly cleared by parenchymal liver cells. In this study the characteristics of the interaction of beta-VLDL with rat parenchymal cells, Hep G2 cells and human parenchymal cells are evaluated. The binding of beta-VLDL to these cells follows saturation kinetics (Bmax. respectively 117, 106 and 103 ng of beta-VLDL apoliprotein/mg of cell protein), with a relatively high affinity (Kd respectively for beta-VLDL of 10.7, 5.1 and 8.4 micrograms/ml). Competition studies of unlabelled beta-VLDL, low-density lipoprotein (LDL) or acetylated LDL with the binding of radiolabelled beta-VLDL indicate that a LDL-receptor-independent, Ca(2+)-independent, specific recognition site for beta-VLDL is present on rat and human parenchymal cells, whereas with Hep G2 cells or mouse macrophages beta-VLDL recognition is performed by the LDL receptor. The binding of beta-VLDL to Hep G2 cells was down-regulated by 89% by prolonged exposure to beta-VLDL, whereas for human parenchymal and rat parenchymal cells down-regulation of 44% and 20% respectively was observed. Studies with antibodies against the LDL receptor support the presence of a LDL-receptor-independent specific beta-VLDL recognition site on rat and human parenchymal cells. It is concluded that a LDL-receptor-independent recognition site for beta-VLDL is present on rat and human parenchymal liver cells. The presence of a LDL-receptor-independent recognition site on human parenchymal cells may mediate in vivo the uptake of beta-VLDL during consumption of a cholesterol-rich diet, when LDL receptors are down-regulated, thus protecting against the extrahepatic accumulation of the atherogenic beta-VLDL constituents.

De Water, R; Kamps, J A; Van Dijk, M C; Hessels, E A; Kuiper, J; Kruijt, J K; Van Berkel, T J

1992-01-01

263

Dynamic structure of the lower density lipoproteins. II. Deuterium NMR studies of the monolayer of very low and low density lipoproteins.  

PubMed

The order of phosphatidylcholine (PC) acyl chains in the surface monolayer of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) has been determined from 2H nuclear magnetic resonance order parameters, SCD, using selectively deuterated PC or palmitic acids. From the computer simulated line shapes, we find two distinct phospholipid domains within the amphiphilic monolayer of both VLDL and LDL. In the more ordered domain of LDL, SCD was approximately 0.3 for the "plateau" chain region. The SCD values of VLDL particles are similar to those of LDL for the 5,6- and 11,12-positions, hence we suggest the organization of the more ordered region of VLDL and LDL are similar. The domain of low order in LDL comprises less than 10% of the phospholipid molecules (we do not distinguish between PC and sphingomyelin), having approximately the same order (SCD less than 0.1) as egg PC - sphingomyelin unilamellar vesicles. In VLDL, the domain of low order comprises between approximately 10 and approximately 20% of the phospholipid molecules and the entire acyl chain is in an essentially isotropic environment (SCD less than 0.02). We prepared VLDL-sized microemulsions composed of egg PC, deuterated PC, and triolein to test whether the apoproteins were responsible for creating the two differently organized domains in VLDL and LDL. Surprisingly, these protein-free particles also showed two domains of different order at two temperatures. The high order region, however, is less ordered than in VLDL and LDL. We explain two surface domains of PC in terms of lipid organization and the unique interactions of lipids in the various lipoprotein particles. PMID:2350486

Chana, R S; Treleaven, W D; Parmar, Y I; Cushley, R J

1990-01-01

264

Hepatic deficiency of low density lipoprotein receptor-related protein-1 reduces high density lipoprotein secretion and plasma levels in mice.  

PubMed

The low density lipoprotein receptor-related protein-1 (LRP1) is known to serve as a chylomicron remnant receptor in the liver responsible for the binding and plasma clearance of apolipoprotein E-containing lipoproteins. Previous in vitro studies have provided evidence to suggest that LRP1 expression may also influence high density lipoprotein (HDL) metabolism. The current study showed that liver-specific LRP1 knock-out (hLrp1(-/-)) mice displayed lower fasting plasma HDL cholesterol levels when compared with hLrp1(+/+) mice. Lecithin:cholesterol acyl transferase and hepatic lipase activities in plasma of hLrp1(-/-) mice were comparable with those observed in hLrp1(+/+) mice, indicating that hepatic LRP1 inactivation does not influence plasma HDL remodeling. Plasma clearance of HDL particles and HDL-associated cholesteryl esters was also similar between hLrp1(+/+) and hLrp1(-/-) mice. In contrast, HDL secretion from primary hepatocytes isolated from hLrp1(-/-) mice was significantly reduced when compared with that observed with hLrp1(+/+) hepatocytes. Biotinylation of cell surface proteins revealed decreased surface localization of the ATP-binding cassette, subfamily A, member 1 (ABCA1) protein, but total cellular ABCA1 level was not changed in hLrp1(-/-) hepatocytes. Finally, hLrp1(-/-) hepatocytes displayed reduced binding capacity for extracellular cathepsin D, resulting in lower intracellular cathepsin D content and impairment of prosaposin activation, a process that is required for membrane translocation of ABCA1 to facilitate cholesterol efflux and HDL secretion. Taken together, these results documented that hepatic LRP1 participates in cellular activation of lysosomal enzymes and through this mechanism, indirectly modulates the production and plasma levels of HDL. PMID:21343303

Basford, Joshua E; Wancata, Lauren; Hofmann, Susanna M; Silva, R A Gangani D; Davidson, W Sean; Howles, Philip N; Hui, David Y

2011-04-15

265

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

PubMed Central

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

2013-01-01

266

Clinical remission is associated with restoration of normal high-density lipoprotein cholesterol levels in children with malignancies.  

PubMed

1. Serum lipids and lipoprotein profiles were determined in children affected by different types of malignancies (leukaemias or lymphomas and solid tumours) both before any treatment and after remission of the disease following chemical or surgical therapy. 2. At the time of diagnosis, children bearing tumours showed hypertriglyceridaemia and reduced concentrations of plasma high-density lipoprotein cholesterol levels, the decrease being particularly prominent in patients with haematological tumours. Children bearing solid tumours displayed an increase of total cholesterol, while those with haematological cancer showed decreased phospholipid levels; low-density lipoprotein cholesterol in neoplastic patients was not significantly different from control values. High triacylglycerol and low high-density lipoprotein cholesterol levels were also evident in cancer patients divided according to age into three groups (0-5, 6-10 and 11-15 years) when compared with age-matched control subjects. Similarly, high triacylglycerol and low high-density lipoprotein cholesterol levels were also observed in both male and female children when patients were divided according to sex and compared with corresponding controls. 3. Clinical remission after therapy was accompanied by an increase of high-density lipoprotein cholesterol levels compared with values observed at diagnosis. In contrast, post-treatment levels of triacylglycerol were higher than those observed before therapy. These results support the hypothesis that alterations of high-density lipoprotein cholesterol levels may be related, at least in part, to the rate of tumour growth, while modifications of triacylglycerol levels may be mediated by different mechanisms. PMID:8549065

Dessì, S; Batetta, B; Spano, O; Sanna, F; Tonello, M; Giacchino, M; Tessitore, L; Costelli, P; Baccino, F M; Madon, E

1995-11-01

267

Impaired Fasting Glucose and Impaired Glucose Tolerance Have Distinct Lipoprotein and Apolipoprotein Changes: The Insulin Resistance Atherosclerosis Study  

PubMed Central

Context: Cardiovascular risk is increased in individuals with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG); however, those with IGT appear to be at greater risk. Lipoprotein abnormalities occur also in the prediabetic state. Objective: The authors examined lipoprotein composition in IGT and IFG. Design and Setting: Cross-sectional analysis of a large epidemiological study was done. Participants: The Insulin Resistance Atherosclerosis Study had a total of 1107 participants. Main measures: Lipoproteins and apolipoproteins were measured by conventional methods and lipoprotein composition by nuclear magnetic resonance spectroscopy. Results: Compared with normal glucose tolerance, apolipoprotein B (105.2 vs 99.8 mg/dL, P < .05) was high in isolated IFG, triglyceride (1.48 vs 1.16 mmol/L, P < .001) was high in isolated IGT, and high-density lipoprotein cholesterol was low in combined IFG/IGT (1.12 vs 1.26 mmol/L, P < .001). Nuclear magnetic resonance spectroscopy revealed additional changes: increased total low-density lipoprotein (LDL) particles (1190 vs 1096 nmol/L, P < .01) in isolated IFG; increased large very-low-density lipoprotein (3.61 vs 2.47 nmol/L, P < .01) and small LDL subclass particles (665 vs 541 nmol/L, P < .05) and decreased large LDL subclass particles (447 vs 513 nmol/L, P < .01) in isolated IGT; and decreased large high-density lipoprotein subclass particles in combined IFG/IGT (4.24 vs 5.39 ?mol/L, P < .001). Conclusions: Isolated IFG is characterized by increased apolipoprotein B and total LDL particles, whereas isolated IGT is associated with increased triglycerides, large very-low-density lipoprotein subclass particles, and structural remodeling of LDL particles. These results may help to explain differences in cardiovascular disease risk in the prediabetic state.

Hartnett, Sara; Hanley, Anthony J.; Rewers, Marian J.; Wagenknecht, Lynne E.; Karter, Andrew J.; Haffner, Steven M.

2013-01-01

268

Assessment of serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in periodontitis patients  

PubMed Central

Background and Objectives: Periodontal disease is a destructive inflammatory disease inducing profound changes in the plasma concentrations of cytokines leading to a catabolic state characterized by altered lipid metabolism and hypertriglyceridemia. The main objective of the present study was to evaluate the effect of periodontal infection on serum levels of triglycerides (TGL), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. Materials and Methods: A sample of 90 subjects; 30 periodontally healthy individuals, 30 chronic gingivitis cases (n=30), and 30 chronic periodontitis cases (n=30) with an age range of 25 to 65 years were included in the study. Periodontal parameters including Plaque Index, Gingival Index, Probing Depth, and Clinical Attachment Level were recorded. Venous blood samples were obtained after 12 hours fasting period from antecubital vein and serum levels of TGL, TC, HDL, and LDL cholesterol were measured. Results: The levels of TGL, TC, and LDL cholesterol were significantly higher for periodontitis group (P<0.05) as compared to gingivitis and periodontally healthy groups. HDL cholesterol levels were significantly lower in periodontitis group (P<0.05) as compared to periodontally healthy and gingivitis groups. Conclusion: The results of the present study indicate that periodontal infection has a definite role in altering lipid metabolism leading to hyperlipidemia. However, further studies are required to clarify the relationship between periodontitis and serum lipid levels and to determine whether oral healthcare has the potential to reduce serum lipid levels in otherwise systemically healthy individuals.

Penumarthy, Swati; Penmetsa, Gautami S.; Mannem, Satheesh

2013-01-01

269

Effect of oxidation on the structure of human low- and high-density lipoproteins.  

PubMed

This work presents a controlled study of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) structural changes due to in vitro oxidation with copper ions. The changes were studied by small-angle x-ray scattering (SAXS) and dynamic light scattering (DLS) techniques in the case of LDL and by SAXS, DLS, and Z-scan (ZS) techniques in the case of HDL. SAXS data were analyzed with a to our knowledge new deconvolution method. This method provides the electron density profile of the samples directly from the intensity scattering of the monomers. Results show that LDL particles oxidized for 18 h show significant structural changes when compared to nonoxidized particles. Changes were observed in the electrical density profile, in size polydispersity, and in the degree of flexibility of the APO-B protein on the particle. HDL optical results obtained with the ZS technique showed a decrease of the amplitude of the nonlinear optical signal as a function of oxidation time. In contrast to LDL results reported in the literature, the HDL ZS signal does not lead to a complete loss of nonlinear optical signal after 18 h of copper oxidation. Also, the SAXS results did not indicate significant structural changes due to oxidation of HDL particles, and DLS results showed that a small number of oligomers formed in the sample oxidized for 18 h. All experimental results for the HDL samples indicate that this lipoprotein is more resistant to the oxidation process than are LDL particles. PMID:24940777

Oliveira, Cristiano L P; Santos, Priscila R; Monteiro, Andrea M; Figueiredo Neto, Antonio M

2014-06-17

270

Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels  

PubMed Central

It has been proposed that the plasma phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids and cholesterol from triglyceride-rich lipoproteins (TRL) into high-density lipoproteins (HDL). To evaluate the in vivo role of PLTP in lipoprotein metabolism, we used homologous recombination in embryonic stem cells and produced mice with no PLTP gene expression. Analysis of plasma of F2 homozygous PLTP–/– mice showed complete loss of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, and partial loss of free cholesterol transfer activities. Moreover, the in vivo transfer of [3H]phosphatidylcholine ether from very-low-density proteins (VLDL) to HDL was abolished in PLTP–/– mice. On a chow diet, PLTP–/– mice showed marked decreases in HDL phospholipid (60%), cholesterol (65%), and apo AI (85%), but no significant change in non-HDL lipid or apo B levels, compared with wild-type littermates. On a high-fat diet, HDL levels were similarly decreased, but there was also an increase in VLDL and LDL phospholipids (210%), free cholesterol (60%), and cholesteryl ester (40%) without change in apo B levels, suggesting accumulation of surface components of TRL. Vesicular lipoproteins were shown by negative-stain electron microscopy of the free cholesterol– and phospholipid-enriched IDL/LDL fraction. Thus, PLTP is the major factor facilitating transfer of VLDL phospholipid into HDL. Reduced plasma PLTP activity causes markedly decreased HDL lipid and apoprotein, demonstrating the importance of transfer of surface components of TRL in the maintenance of HDL levels. Vesicular lipoproteins accumulating in PLTP–/– mice on a high-fat diet could influence the development of atherosclerosis.

Jiang, Xian-cheng; Bruce, Can; Mar, Jefferson; Lin, Min; Ji, Yong; Francone, Omar L.; Tall, Alan R.

1999-01-01

271

Structural investigation of reconstituted high density lipoproteins by scanning tunnelling microscopy  

NASA Astrophysics Data System (ADS)

Being able to participate in the reverse cholesterol transport (RCT), high density lipoproteins (HDL) are known to be anti-atherogenic. In order to understand such a process, it is thus essential to have a detailed knowledge of the structure and molecular organisation of HDL. Reconstituted nascent high density lipoproteins (r-HDL), consisting of synthetic phospholipids together with different apolipoproteins (apo A-I, A-IV and E), were thus analysed by scanning tunnelling microscopy (STM). Both shape and dimensions of the discoidal HDL particles measured by this technique were found in good agreement with the data available from the literature. The accuracy of the STM pictures presented in this paper enables for the first time the visualisation of the molecular organisation of such macromolecules. The arrangement of the protein as antiparallel helical segments, is consistent with the general mode of organisation of apolipoprotein/phospholipid discoidal particles previously reported.

Culot, C.; Durant, F.; Lazarescu, S.; Thiry, P. A.; Vanloo, B.; Rosseneu, M. Y.; Lins, L.; Brasseur, R.

2004-05-01

272

High-density lipoprotein heterogeneity and function in reverse cholesterol transport  

PubMed Central

Purpose of review HDL is a cardioprotective lipoprotein, at least in part, because of its ability to mediate reverse cholesterol transport (RCT). It is becoming increasingly clear that the antiatherogenic effects of HDL are not only dependent on its concentration in circulating blood but also on its biological ‘quality’. This review summarizes our current understanding of how the biological activities of individual subclasses of HDL particles contribute to overall HDL performance in RCT. Recent findings Recent work indicates that apolipoprotein A-I-containing nascent HDL particles are heterogeneous and that such particles exert different effects on the RCT pathway. RCT from macrophages has been examined in detail in mice and the roles of plasma factors (lecithin-cholesterol acyltransferase, cholesterol ester transfer protein, phospholipid transfer protein) and cell factors (ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, scavenger receptor class B type 1) have been evaluated. Manipulation of such factors has consistent effects on RCT and atherosclerosis, but the level of plasma HDL does not reliably predict the degree of RCT. Furthermore, HDL cholesterol or apolipoprotein A-I levels do not necessarily correlate with the magnitude of cholesterol efflux from macrophages; more understanding of the contributions of specific HDL subspecies is required. Summary The antiatherogenic quality of HDL is defined by the functionality of HDL subspecies. In the case of RCT, the rate of cholesterol movement through the pathway is critical and the contributions of particular types of HDL particles to this process are becoming better defined.

Rothblat, George H.; Phillips, Michael C.

2011-01-01

273

Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia  

Microsoft Academic Search

HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL (OxLDL), subclinical in- flammation (high-sensitive C-reactive protein (Hs-CRP)), and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, ? 107C\\/T, ?

Thomas M. van Himbergen; Mark Roest; Jacqueline de Graaf; Eugène H. J. M. Jansen; Hiroaki Hattori; John J. P. Kastelein; Hieronymus A. M. Voorbij; Anton F. H. Stalenhoef

2004-01-01

274

Antioxidant protection of low density lipoprotein by procyanidins: structure\\/activity relationships  

Microsoft Academic Search

The antioxidant activity of catechins and oligomeric procyanidins against low density lipoproteins peroxidation was studied by means of three distinct methods: cis-parinaric acid fluorescence decay, conjugated-dienes detection, and oxygen consumption. A relationship between the radical trapping efficiency of procyanidins and their structure was investigated. The results indicated that: (i) interflavan linkage type (C4?C6 or C4?C8) exerts a significant effect upon

Patr??cia Andréia Leite da Silva Porto; João António Nave Laranjinha; Victor Armando Pereira de Freitas

2003-01-01

275

Association of Serum Concentration of Total Bilirubin and Low Density Lipoprotein Cholesterol with Myocardial Infarction  

Microsoft Academic Search

We examined serum bilirubin and low density lipoprotein cholesterol (LDL-C) as possible risk factors in 27 patients of myocardial infarction and 50 healthy individuals served as control. An inverse relationship between increase in total bilirubin and serum levels of LDL-C was observed. There is possibility of bilirubin playing a role in the pathogenesis of coronary heart disease through LDL-C levels.

Simmi Kharb

276

Phenotypic characterization of the Ath1 gene controlling high density lipoprotein levels and susceptibility to atherosclerosis  

Microsoft Academic Search

The Ath-2 gene determines the levels of high density lipoprotein (HDL) lipid in response to a high fat diet challenge as well as susceptibility to diet-induced atherosclerosis in mice (Paigen et al. 1987. Pmc. Natl. Acad. Sci. USA. 84: 3763-3767). As yet, the identity of the Aih-1 gene and how it acts to affect HDL levels are completely unknown. In

Renee C. LeBoeuf; Mark H. Doolittle; Alice Montcalm; Dominique C. Martin; Karen Reue; Aldons J. Lusistf

277

Lipid-lipid interactions in reconstituted high-density lipoproteins by deuterium nuclear magnetic resonance  

Microsoft Academic Search

Lipid-lipid interactions between the core and monolayer have been studied by using reconstituted high-density lipoproteins (rHDLs) composed of apoHDLâ with either dipalmitoylphosphatidylcholine (DPPC) or egg phosphatidylcholine (egg PC) as the monolayer and either cholesteryl oleate (CO) or triolein (TO) as the core. The effect of the monolayer on the core was observed by deuterium nuclear magnetic resonance (²H NMR) studies

David B. Fenske; Yashpal I. Parmar; W. Dale Treleaven; Ravinder S. Chana; Robert J. Cushley

1988-01-01

278

Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins  

Microsoft Academic Search

Resveratrol, a phytoalexin (3, 4?, 5, trihydroxystilbene) present in some red wines, has been reported to inhibit copper-mediated low-density lipoprotein (LDL) oxidation. In this study, we examined the efficiency of this compound in inhibiting metal ion-dependent and independent peroxidation of porcine LDL. At 0.5, 1, or 1.5 ?M, transresveratrol prolonged the lag time preceding the onset of conjugated diene formation

Leila Belguendouz; Lucie Fremont; Alain Linard

1997-01-01

279

Antioxidation of human low density lipoprotein by unconjugated and conjugated bilirubins  

Microsoft Academic Search

We demonstrate here that both unconjugated bilirubin (Bu) and conjugated bilirubin (Bc) can protect human low density lipoprotein (LDL) against oxidation by oxyradicals generated by 2,2?-azo-bis(2-amidinopropane) dihydrochloride at 37°. The oxidation was assessed by agarose gel electrophoresis and was further corroborated by assaying the malondialdehydes and lipid peroxides formed throughout oxidation. On a per mole basis, Bu and less so

Tai-Wing Wu; K. P. Fung; Jun Wu; Chih-Chin Yang; Richard D. Weisel

1996-01-01

280

Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population  

Microsoft Academic Search

The interrelationships among fatness measures, plasma triglycerides and high density lipoproteins (HDL) were examined in 131\\u000a normal adult subjects: 38 men aged 27–46, 40 men aged 47–66, 29 women aged 27–46 and 24 women aged 47–66. None of the women\\u000a were taking estrogens or oral contraceptive medication. The HDL concentration was subdivided into HDL2b, HDL2a and HDL3 by a computerized

M. J. Albrink; R. M. Krauss; F. T. Lindgren; J. Von Der Groeben; S. Pan; P. D. Wood

1980-01-01

281

Analysis of high density lipoproteins by a modified gradient gel electrophoresis method  

Microsoft Academic Search

A high resolution electrophoretic method has been developed to separate plasma high density lipoprotein (HDL) particles by size using 4-3076 polyacrylamide agarose (PAA) gradient gels, Sudan black B staining, and laser densitometry. Fourteen distinct HDL bands were observed with HDL-1 being designated as the largest particle and HDL-14 as the smallest particle. HDL-1 was similar in size to ferritin (Stokes

Zhengling Li; Judith R. McNamara; Jose M. Ordovas; Ernst J. Schaeferl

282

High density lipoprotein particle size distribution in subjects with obstructive jaundice  

Microsoft Academic Search

High density lipoproteins (HDL) from 14 patients with obstructive jaundice were examined by gradient gel electropho- resis to determine the effect of obstruction on particle size distri- bution. HDL from 7 of these patients were fractionated by gel permeation chromatography and further characterized by elec- tron microscopy, SDS gel electrophoresis, apolipoprotein A-I and apolipoprotein A-I1 immunoturbidimetry, and analysis of chem-

Peter M. Clifton; Philip J. Barter; A. Malcolm Mackinnon

283

High density lipoprotein subfractions in non-insulin- dependent diabetes mellitus and coronary artery disease  

Microsoft Academic Search

High density lipoprotein (HDL) subfractions (2b, 2a, 3a, 3b, and 3c) separated by gradient gel electrophoresis (GGE) and defined by Gaussian summation analysis, and the compositions of HDL2 and HDL,, separated by preparative ultracentrifugation, were studied in four groups of men with or without non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD): group 1 (DM+CAD+, n = 50); group

Mikko Syvanne; Maria Ahola; Sanni Lahdenpera; Juhani Kahri; Kari S. Virtanen; Marja-Riitta Taskinent

284

High-density lipoprotein subfractions and risk of coronary artery disease  

Microsoft Academic Search

Numerous studies have shown that levels of high-density lipoprotein (HDL) cholesterol are inversely related to coronary artery\\u000a disease risk. The HDL subfractions, however, seem to differ in their capacity to confer protection, with the large HDL2 subfraction\\u000a appearing to be more important than the small HDL3 subfraction. Lipid-modifying drugs differ in their HDL-raising efficacy,\\u000a and they also differ in how

John Morgan; Christina Carey; Anne Lincoff; David Capuzzi

2004-01-01

285

Whole Genome Sequence-Based Analysis of a Model Complex Trait, High Density Lipoprotein Cholesterol  

PubMed Central

We describe initial steps for interrogating whole genome sequence (WGS) data to characterize the genetic architecture of a complex trait, such as high density lipoprotein cholesterol (HDL-C). We estimate that common variation contributes more to HDL-C heritability than rare variation, and screening for Mendelian dyslipidemia variants identified individuals with extreme HDL-C. WGS analyses highlight the value of regulatory and non-protein coding regions of the genome in addition to protein coding regions.

Morrison, Alanna C.; Voorman, Arend; Johnson, Andrew D.; Liu, Xiaoming; Yu, Jin; Li, Alexander; Muzny, Donna; Yu, Fuli; Rice, Kenneth; Zhu, Chengsong; Bis, Joshua; Heiss, Gerardo; O'Donnell, Christopher J.; Psaty, Bruce M.; Cupples, L. Adrienne; Gibbs, Richard; Boerwinkle, Eric

2013-01-01

286

Tomato lycopene and low density lipoprotein oxidation: A human dietary intervention study  

Microsoft Academic Search

Increase in low density lipoprotein (LDL) oxidation is hypothesized to be causally associated with increasing risk of atherosclerosis\\u000a and coronary heart disease. In recent epidemiological studies, tissue and serum levels of lycopene, a carotenoid available\\u000a from tomatoes, have been found to be inversely related to risk of coronary heart disease. A study was undertaken to investigate\\u000a the effect of dietary

Sanjiv Agarwal; A. Venketeshwer Rao

1998-01-01

287

Protective effect of oleuropein, an olive oil biophenol, on low density lipoprotein oxidizability in rabbits  

Microsoft Academic Search

On the basis of the results obtained with pilot studies conducted in vitro on human low density lipoprotein (LDL) and on cell cultures (Caco-2), which had indicated the ability of certain molecules\\u000a present in olive oil to inhibit prooxidative processes, an in vivo study was made of laboratory rabbits fed special diets. Three different diets were prepared: a standard diet

E. Coni; R. Di Benedetto; M. Di Pasquale; R. Masella; D. Modesti; R. Mattei; E. A. Carlini

2000-01-01

288

Formation of F 2-isoprostanes in oxidized low density lipoprotein: Inhibitory effect of hydroxytyrosol  

Microsoft Academic Search

Oxidatively-modified low-density lipoproteins (LDL) contribute to the onset of the atherosclerotic disease. A recently discovered marker of lipid peroxidation is a series of prostaglandin F2-like compounds, the prostaglandin isomers isoprostanes, that are generated from arachidonic acid through cyclooxygenase-independent pathways following free radical injury and are endowed with potent biological activities. The incidence of cardiovascular disease in the Mediterranean area is

Marco Salami; Claudio Galli; Leonardo De Angelis; Francesco Visioli

1995-01-01

289

Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster  

Microsoft Academic Search

The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an

Cynthia M. Arbeeny; Daniel S. Meyers; Kristin E. Bergquist; Richard E. Gregg

290

Plasma Paraoxonase-1, Oxidized Low-Density Lipoprotein and Lipid Peroxidation Levels in Gout Patients  

Microsoft Academic Search

Gout patients have a high incidence of atherosclerotic coronary heart disease. Low serum paraoxonase (PON) activity is considered\\u000a a risk factor for atherosclerosis. The relationships among paraoxonase-1 (PON1) activity, oxidative stress parameters, and\\u000a atherosclerosis in gout is not known. Therefore, we determined the plasma levels of malondialdehyde (MDA), oxidized low-density\\u000a lipoprotein (Ox-LDL), and activities of PON1\\/superoxide dismutase (SOD) activities in

Xing-Liang JiangMin; Min Li; Jing-Guo Zhou; Qi-Bin Yang; Li-Jun Du; Juan Du

291

Circulating Oxidized Low-Density Lipoprotein and Paraoxonase Activity in Preeclampsia  

Microsoft Academic Search

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In

H. Uzun; A. Benian; M. Albayrak

2005-01-01

292

Autoantibodies to low-density-lipoprotein-receptor-related protein 2 (LRP2) in systemic autoimmune diseases  

Microsoft Academic Search

We previously reported that autoantibodies (autoAbs) to the main epitope on CD69 reacted to its homologous amino acid sequence in low-density-lipoprotein-receptor-related protein 2 (LPR2), a multiligand receptor for protein reabsorption. In this study, we have investigated the prevalence, autoepitope distribution, and clinical significance of the autoAbs to LRP2 in patients with systemic autoimmune diseases. Using six recombinant proteins (F2–F7) for

Seido Ooka; Toshihiro Matsui; Kusuki Nishioka; Tomohiro Kato

2003-01-01

293

Autoantibodies to oxidized low-density lipoprotein in coronary artery disease  

Microsoft Academic Search

Background:The significance of antioxidized low-density lipoprotein (oxLDL) antibodies in atherogenesis is not yet clear, and there are conflicting data regarding anti-oxLDL levels in early hypertension.Methods:The levels of anti-oxLDL antibodies were studied in coronary artery disease patients with (n = 82) or without (n = 36) hypertension, in association to other risk factors for coronary artery disease.Results:The levels of anti-oxLDL antibodies

Yaniv Sherer; Alexander Tenenbaum; Miri Blank; Joseph Shemesh; Dror Harats; Enrique Z. Fisman; Sonja Praprotnik; Michael Motro; Yehuda Shoenfeld

2001-01-01

294

Contribution of vitamin A to the oxidation resistance of human low density lipoproteins  

Microsoft Academic Search

This study investigated the antioxidant contribution of vitamin A in protecting human low density lipoprotein (LDL) against copper-stimulated oxidation. The presence of small amounts of retinol (0.033 ± 0.012 nmol\\/mol LDL) and retinyl palmitate (0.036 ± 0.021 nmol\\/mol LDL) was routinely ascertained in the LDL. A single oral supplementation with 20,000 IU vitamin A caused a two- to three-fold increase

Maria A. Livrea; Luisa Tesoriere; Antonino Bongiorno; Anna Maria Pintaudi; Marcello Ciaccio; Antonio Riccio

1995-01-01

295

Improved glucose control decreases the interaction of plasma low-density lipoproteins with arterial proteoglycans  

Microsoft Academic Search

The entrapment and retention of plasma low-density lipoproteins (LDL) by arterial proteoglycans (PG) is a process central to atherogenesis. We postulated therefore that accelerated atherosclerosis of diabetic individuals may result from hyperglycemia-associated modifications in LDL that enhance their interaction with arterial PG. To evaluate the role of clinical treatment on this process, LDL-PG binding was evaluated in uncontrolled type 2

Iris J. Edwards; James G. Terry; Audrey D. Bell-Farrow; William T. Cefalu

2002-01-01

296

Protective effect of olive oil and its phenolic compounds against low density lipoprotein oxidation  

Microsoft Academic Search

The protective effect of phenolic compounds from an olive oil extract, and of olive oils with (extra-virgin) and without (refined)\\u000a phenolic components, on low density lipoprotein (LDL) oxidation was investigated. When added to isolated LDL, phenolics [0.025–0.3\\u000a mg\\/L caffeic acid equivalents (CAE)] increased the lag time of conjugated diene formation after copper-mediated LDL oxidation\\u000a in a concentration-dependent manner. Concentrations of

Montserrat Fitó; María Isabel Covas; Rosa M. Lamuela-Raventós; Joan Vila; Jaume Torrents; Carmen de la Torre; Jaume Marrugat

2000-01-01

297

Influence of the High Density Lipoprotein Receptor SR-BI on Reproductive and Cardiovascular Pathophysiology  

Microsoft Academic Search

The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. As a consequence, SR-BI can influence plasma HDL cholesterol levels, HDL structure, biliary cholesterol concentrations, and the uptake, storage, and utilization of cholesterol by steroid hormone-producing cells. Here we used homozygous null SR-BI

Bernardo Trigatti; Helen Rayburn; Marisa Vinals; Anne Braun; Helena Miettinen; Marsha Penman; Miki Hertz; Mark Schrenzel; Ludwig Amigo; Attilio Rigotti; Monty Krieger

1999-01-01

298

Studies of low density lipoprotein molecular weight in human beings with coronary artery disease  

Microsoft Academic Search

Low density lipoprotein molecular weight (LDL MW) correlates positively with coronary artery disease in cho- lesterol-fed nonhuman primates. To evaluate this in human beings with coronary artery disease (CAD) we measured LDL MW in 93 volunteers undergoing coronary angiography (47 controls and 46 CAD patients). LDL MW of CAD patients was less than that of controls (patients, 2.79 * 0.17

John R. Crouse; Johns S. Parks; Harry M. Schey; Frederic R. Kahl

299

Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins  

Microsoft Academic Search

The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in atherogenesis. Drugs of ß-hydroxy-ß-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they simultaneously block biosynthesis of both cholesterol and ubiquinone Q10 (coenzyme Q), which is an intermediate electron carrier in the mitochondrial respiratory chain.

Vadim Z. Lankin; Alla K. Tikhaze; Valery V. Kukharchuk; Galina G. Konovalova; Oleg I. Pisarenko; Alexander I. Kaminnyi; Konstantin B. Shumaev; Yury N. Belenkov

2003-01-01

300

Circulating Oxidized Low Density Lipoprotein Levels A Biochemical Risk Marker for Coronary Heart Disease  

Microsoft Academic Search

Recent studies have established oxidative modification of low density lipoprotein (LDL) as an important atherogenic factor. We examined the clinical relevance of circulating oxidized LDL (OxLDL) levels in atherosclerotic disease by an enzyme immunoassay with use of specific antibodies against OxLDL (FOH1a\\/DLH3) and apolipoprotein B. Plasma OxLDL levels were significantly higher in patients with coronary heart disease (n565) than in

Shun-ichi Toshima; Akira Hasegawa; Masahiko Kurabayashi; Hiroyuki Itabe; Tatsuya Takano; Jinpei Sugano; Kyoko Shimamura; Junji Kimura; Ichiro Michishita; Toru Suzuki; Ryozo Nagai

2010-01-01

301

Particle size analysis of high density lipoproteins in patients with genetic cholesteryl ester transfer protein deficiency  

Microsoft Academic Search

We investigated the detailed distribution of high-density lipoproteins (HDL) particle size in patients with cholesteryl ester transfer protein (CETP) deficiency. Serum samples pre-stained with Sudan black B were electrophoresed using 4–30% polyacrylamide gradient gels, and the Stokes diameter of HDL particles was determined in 23 patients with genetic CETP deficiency, nine patients with hyperalphalipoproteinemia and seven subjects with normal HDL

Tomoko Arai; Toshihiko Tsukada; Toshio Murase; Kojiro Matsumoto

2000-01-01

302

Absence of Monocyte Chemoattractant Protein1 Reduces Atherosclerosis in Low Density Lipoprotein Receptor–Deficient Mice  

Microsoft Academic Search

Recruitment of blood monocytes into the arterial subendothelium is one of the earliest steps in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, is one likely signal involved in this process. To test MCP-1’s role in atherogenesis, low density lipoprotein (LDL) receptor–deficient mice were made genetically deficient for MCP-1 and fed a high cholesterol diet. Despite having the same amount

Long Gu; Yoshikatsu Okada; Steven K. Clinton; Craig Gerard; Galina K. Sukhova; Peter Libby; Barrett J. Rollins

1998-01-01

303

Oxidized Low-Density Lipoprotein and Oxidative Stress in the Development of Glomerulosclerosis  

Microsoft Academic Search

Glomerulosclerosis frequently complicates most renal diseases and is characterized by mesangial matrix accumulation. Oxidized low-density lipoprotein (Ox-LDL) could induce oxidative stress and profibrotic gene expression in mesangial cells. This article will review our current understanding of the pathogenetic mechanisms of lipid-mediated glomerulosclerosis, emphasizing the fibrogenic signaling cascades triggered by Ox-LDL. In addition, therapeutic strategies to prevent the development of Ox-LDL-mediated

Hyun Soon Lee; Chi Young Song

2009-01-01

304

Cel I u lar localization and characterization of proteins that bind high density lipoprotein  

Microsoft Academic Search

High density lipoprotein (HDL) stimulates excretion of excess intracellular cholesterol from cells, presumably by in- teracting with a cell-surface receptor. A 110 kDa membrane pro- tein that is a candidate for the HDL receptor has been identified by ligand blot analysis. In this study we determined the cellular localization of this and other HDL-binding proteins and charac- terized their properties.

Bjern Hokland; Armando J. Mendez; John F. Oram

305

A Green Tea Catechin Extract Upregulates the Hepatic Low-Density Lipoprotein Receptor in Rats  

Microsoft Academic Search

Green tea extracts have hypocholesterolaemic properties in epidemiological and animal intervention studies. Upregulation of\\u000a the low-density lipoprotein (LDL) receptor may be one mechanism to explain this as it is the main way cholesterol is removed\\u000a from the circulation. This study aimed to determine if a green tea extract could upregulate the hepatic LDL receptor in vivo\\u000a in the rat. A

Christina A. Bursill; Paul D. Roach

2007-01-01

306

Selective uptake of boronated low-density lipoprotein in melanoma xenografts achieved by diet supplementation  

Microsoft Academic Search

The lipid core of human plasma low-density lipoprotein (LDL) was extracted using hexane and the LDL reconstituted with the addition of n-octyl-carborane. Biodistribution studies of the boronated LDL were performed in BALB\\/c mice bearing subcutaneous Harding-Passey melanoma xenografts. When diet supplementation with coconut oil and cholesterol for 21 days and regular dosing with hydrocortisone for 7 days before the studies

Y Setiawan; DE Moore; BJ Allen

1996-01-01

307

Effects of lifestyle interventions on high-density lipoprotein cholesterol levels  

Microsoft Academic Search

This review summarizes intervention studies that evaluated the effects of lifestyle behaviors on high-density lipoprotein-cholesterol (HDL-C) levels. Current diet and lifestyle recommendations beneficially affect HDL-C. Individual lifestyle interventions that increase HDL-C include: a healthful diet that is low (7–10% of calories) in saturated fat and sufficient in unsaturated fat (15–20% of calories), regular physical activity, attaining a healthy weight, with

Michael A. Roussell; Penny Kris-Etherton

2007-01-01

308

Physical Activity, High-Density Lipoprotein Cholesterol Subfractions and Lecithin:Cholesterol Acyltransferase in Dialysis Patients  

Microsoft Academic Search

Background\\/Aims: Although a low level of high-density lipoprotein cholesterol (HDL-C) is an independent risk factor for atherosclerotic heart disease, the mechanism of HDL-C abnormality in hemodialysis (HD) as well as peritoneal dialysis (PD) patients is not fully understood. The purpose of this study was to investigate the relationship of physical activity with HDL-C subfractions and lecithin:cholesterol acyltransferase activity in HD

Reika Masuda; Hiroyuki Imamura; Keiko Mizuuchi; Keiko Miyahara; Harumitsu Kumagai; Hideki Hirakata

2009-01-01

309

Effects of F-strain Mycoplasma gallisepticum inoculation on serum very low density lipoprotein diameter and fractionation of cholesterol among lipoproteins in commercial egg-laying hens.  

PubMed

Experimental inoculation with the F-strain of Mycoplasma gallisepticum (FMG) at 12 wk of age has been shown to affect the performance, liver, reproductive organs, and yolk lipid characteristics of commercial layers. Therefore, this study was conducted to determine the serum lipoprotein characteristics of commercial egg-laying hens at 16 wk of age and throughout lay after inoculation with FMG at 12 wk of age. Mean diameters of very low density lipoproteins (VLDL) were determined for the 10th, 50th, and 90th percentiles of serum total VLDL of each hen. Percentages of total serum cholesterol recovered in VLDL and low and high density lipoprotein particle classes were also determined. Inoculation of birds with FMG at 12 wk did not change the physical properties or relative concentrations of their circulating lipoproteins. However, the age of the bird had significant differential effects on all the parameters examined. These data demonstrate that FMG-inoculation at 12 wk of age does not affect the lipoproteins of laying hens, but because these birds were housed in biological isolation units, these results do not preclude the possibility that these yolk precursors may be affected in FMG-infected birds that are housed in facilities in which there are increased levels of environmental stress. These data further suggest that alterations in liver, reproductive organs, and yolk lipid characteristics in response to FMG, as noted in previous reports on commercial layers, are not mediated through changes in circulating VLDL diameters. PMID:14601743

Burnham, M R; Peebles, E D; Branton, S L; Walzem, R L; Gerard, P D

2003-10-01

310

Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipide- mia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production  

Microsoft Academic Search

We investigated the metabolism of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) apolipoprotein B (apoB) in seven patients with combined hyperlipidemia (CHL), using lZ5I- labeled VLDL and '311-labeled LDL and compartmental mo- deling, before and during lovastatin treatment. Lovastatin ther- apy significantly reduced plasma levels of LDL cholesterol (142 vs 93 mg\\/dl, P

Yadon Arad; Rajasekhar Ramakrishnan; Henry N. Ginsberg

311

Low High-Density Lipoprotein Cholesterol Is Not Responsible for Decreased Paraoxonase Activity in Chronic Renal Failure  

Microsoft Academic Search

Background\\/Aims: Human paraoxonase-1 (PON1) is responsible for the antioxidant effect of high-density lipoprotein (HDL) by inhibiting low-density lipoprotein oxidation. Previous studies discovered dyslipidemia (DL) and decreased PON1 activity in chronic renal failure (CRF). We aimed to determine PON and arylesterase activity, phenotypic distribution of the PON1 enzyme, and lipid profile in low and normal HDL cholesterol (HDL-C) patients with CRF,

Éva Varga; Ildikó Seres; Mariann Harangi; István Kárpáti; Péter Koncsos; Ferenc Sztanek; György Paragh

2012-01-01

312

Hyperalphalipoproteinemia: Characterization of a cardioprotective profile associating increased high-density lipoprotein 2 levels and decreased hepatic lipase activity  

Microsoft Academic Search

The aim of the present study was to investigate the high-density lipoprotein (HDL) strucutral characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol) [HDL-C], 92 ± 14 mg\\/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 ± 33 mg\\/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to

Didier Sich; Youssef Saïdi; Philippe Giral; Laurent Lagrost; Monique Egloff; Claude Auer; Valérie Gautier; Gérard Turpin; Isabel Beucler

1998-01-01

313

Inability of plasma high-density lipoproteins to inhibit cell adhesion molecule expression in human coronary artery endothelial cells  

Microsoft Academic Search

High-density lipoproteins (HDL) have several antiatherogenic actions, including the ability to sequester cellular cholesterol, to protect low-density lipoproteins from oxidation and to inhibit platelet aggregation. An early event in atherogenesis is the adhesion and recruitment of blood monocytes, a process mediated by cell adhesion molecules (CAMs), including vascular cell adhesion molecule-1 (VCAM-1) which is rapidly synthesized by endothelial cells in

Anita K. Stannard; Shabeena Khan; Annette Graham; James S. Owen; Sean P. Allen

2001-01-01

314

Estimation oftheConcentration of Low-Density Lipoprotein Cholesterol inPlasma, Without UseofthePreparative Ultracentrifuge  

Microsoft Academic Search

A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded

William T. Friedewald; Robert I. Levy; Donald S. Fredrickson

1972-01-01

315

Preparative and quantitative isolation of plasma lipoproteins: rapid, single discontinuous density gradient ultracentrifugation in a vertical rotor  

Microsoft Academic Search

A rapid method has been developed for separa- tion of the major plasma lipoproteins from up to 96 ml of plasma by a single ultracentrifugation step. This separa- tion was achieved by a discontinuous density gradient centrifugation between the density range of 1.006 and 1.30 g\\/ml in Sorvall vertical rotors. Each lipoprotein fraction was sharply banded with VLDL at the

Byung H. Chung; Thomas Wilkinson; Jack C. Geer; Jere P. Segrest

316

A sensitive chemiluminescence imaging immunoassay for simultaneous detection of serum oxidized lipoprotein(a) and low density lipoprotein.  

PubMed

Abstract Background: Oxidized lipoprotein(a) [ox-Lp(a)] and oxidized low density lipoprotein (ox-LDL) levels have been reported to be useful predictors of cardiovascular events. The study developed a chemiluminescence (CL) imaging immunoassay method for simultaneously detecting serum concentrations of ox-Lp(a) and ox-LDL. Methods: Ox-Lp(a) and ox-LDL levels were measured by CL imaging immunoassay using a disposable immunosensor array as the carrier and a charge-coupled device as the detector, and were studied in 46 acute coronary syndromes (ACS) patients, 58 stable coronary artery disease (CAD) and 61 control subjects. Results: This method showed good linear relations (R2>0.99) in the concentration range of 2.00×10-5-2.00×10-1 and 2.40×10-4-2.40 U/mL for ox-Lp(a) and ox-LDL, respectively. The detection limits for ox-Lp(a) and ox-LDL were 2.40×10-6 and 3.00×10-5 U/mL, respectively. The intra- and inter-assay coefficients of variation (CV) were 4.90%-6.76% and 7.11%-10.06% for ox-Lp(a), and 5.01%-6.04% and 5.47%-9.77% for ox-LDL, respectively. The mean recovery was 99.31% for ox-Lp(a) and 99.57% for ox-LDL, respectively. Significant correlations were observed between ox-Lp(a) levels detected by CL imaging immunoassay and ELISA, and between ox-LDL levels detected by the two methods, respectively. Furthermore, ox-Lp(a) and ox-LDL levels increased in stable CAD, and especially in ACS. Conclusions: The CL imaging immunoassay provided a simple, sensitive and reliable method for the simultaneous determination of serum ox-Lp(a) and ox-LDL. The clinical monitoring ox-Lp(a) and ox-LDL levels may possess distinctly clinical value for assessment of CAD risk. PMID:24421216

Yu, Ruijie; Song, Jiaxi; Wu, Jia; Niu, Dongmei; Ma, Lijuan; Zong, Chen; Ju, Huangxian; Wang, Junjun

2014-06-01

317

Long term hemodialysis aggravates lipolytic activity reduction and very low density, low density lipoproteins composition in chronic renal failure patients  

PubMed Central

Background Dyslipidemia, particularly hypertriglyceridemia is common in uremia, and represents an independent risk factor for atherosclerosis. Methods To investigate the effects of hemodialysis (HD) duration on very low density lipoprotein (VLDL) and low density lipoprotein (LDL) compositions and lipopolytic activities, 20 patients on 5 to 7 years hemodialysis were followed-up during 9 years. Blood samples were drawn at T0 (beginning of the study), T1 (3 years after initiating study), T2 (6 years after initiating study) and T3 (9 years after initiating study). T0 was taken as reference. Results Triacylglycerols (TG) values were correlated with HD duration (r = 0.70, P < 0.05). An increase of total cholesterol was noted at T2 and T3. Lowered activity was observed for lipoprotein lipase (LPL) (-44%) at T3 and hepatic lipase (HL) (-29%) at T1, (-64%) at T2 and (-73%) at T3. Inverse relationships were found between HD duration and LPL activity (r = -0.63, P < 0.05), and HL activity (r = -0.71, P < 0.01). At T1, T2 and T3, high VLDL-amounts and VLDL-TG and decreased VLDL-phospholipids values were noted. Increased LDL-cholesteryl esters values were noted at T1 and T2 and in LDL-unesterified cholesterol at T2 and T3. Conclusion Despite hemodialysis duration, VLDL-LDL metabolism alterations are aggravated submitting patients to a greater risk of atherosclerosis.

Mekki, Khedidja; Prost, Josiane; Remaoun, Mustapha; Belleville, Jacques; Bouchenak, Malika

2009-01-01

318

Low-density lipoprotein, its susceptibility to oxidation and the role of lipoprotein-associated phospholipase A2 and carboxyl ester lipase lipases in atherosclerotic plaque formation  

PubMed Central

An increased level of low-density lipoprotein (LDL) is a very well established risk factor of coronary artery disease (CAD). Unoxidized LDL is an inert transport vehicle of cholesterol and other lipids in the body and is thought to be atherogenic. Recently it has been appreciated that oxidized products of LDL are responsible for plaque formation properties previously attributed to the intact particle. The goal of this article is to review the recent understanding of the LDL oxidation pathway. The role of oxidized products and key enzymes (lipoprotein-associated phospholipase A2 and carboxyl ester lipase) are also extensively discussed in the context of clinical conditions.

Zurawski, Jakub; Zuchowski, Bartosz; Kubacki, Tomasz; Murawa, Dawid; Wiktorowicz, Krzysztof; Wysocki, Henryk

2013-01-01

319

Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease  

PubMed Central

Low high-density lipoprotein (HDL)-cholesterol levels are associated with an increased risk of coronary artery disease (CAD) and myocardial infarction, which has triggered the hypothesis that HDL, in contrast to low-density lipoprotein (LDL), acts as an anti-atherogenic lipoprotein. Moreover, experimental studies have identified potential anti-atherogenic properties of HDL, including promotion of macrophage cholesterol efflux and direct endothelial-protective effects of HDL, such as stimulation of endothelial nitric oxide production and repair, anti-apoptotic, anti-inflammatory and anti-thrombotic properties. Studies in gene-targeted mice, however, have also indicated that increasing HDL-cholesterol plasma levels can either limit (e.g. apolipoprotein A-I) or accelerate (e.g. Scavenger receptor class B type I) atherosclerosis. Moreover, vascular effects of HDL have been observed to be heterogenous and are altered in patients with CAD or diabetes, a condition that has been termed ‘HDL dysfunction’. These alterations in biological functions of HDL may need to be taken into account for HDL-targeted therapies and considering raising of HDL-cholesterol levels alone is likely not sufficient in this respect. It will therefore be important to further determine, which biological functions of HDL are critical for its anti-atherosclerotic properties, as well as how these can be measured and targeted.

Besler, Christian; Luscher, Thomas F; Landmesser, Ulf

2012-01-01

320

Atorvastatin effect on the distribution of high-density lipoprotein subfractions and human paraoxonase activity.  

PubMed

Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (LDL); therefore, it may protect against atherosclerosis. Changes in the ratio of high-density lipoprotein (HDL) subfractions may alter the stability and the antioxidant capacity of PON1. The aim of the study was to examine the effect of atorvastatin treatment on the distribution of HDL subfractions, LDL size, cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and PON1 activity. In all, 33 patients with type IIa and IIb hypercholesterolemia were involved in the study. LDL sizes and HDL subfractions were determined by gradient gel electrophoresis. CETP, LCAT, and PON1 activities were measured spectrophotometrically. Three months of treatment with atorvastatin 20 mg daily significantly increased the HDL3 (+8.13%) and decreased the HDL2a and HDL2b subfractions (-1.57% and -6.55%, respectively). The mean LDL size was significantly increased (+3.29%). The level of oxidized LDL was significantly decreased (-46.0%). The PON1 activity was augmented by the atorvastatin treatment (+5.0%). The CETP activity positively correlated with the HDL2b level and negatively correlated with the HDL3 and HDL2a levels. Atorvastatin alters the HDL subfractions, which may improve its antiatherogenic effect via enhancement of the PON1 activity. PMID:19304278

Harangi, Mariann; Mirdamadi, Hossein Z; Seres, Ildikó; Sztanek, Ferenc; Molnár, Miklós; Kassai, Andrea; Derdák, Zoltán; Illyés, László; Paragh, György

2009-04-01

321

Current guidelines for high-density lipoprotein cholesterol in therapy and future directions.  

PubMed

Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) is low high-density lipoprotein cholesterol (HDL-C). Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. PMID:24748800

Subedi, Bishnu H; Joshi, Parag H; Jones, Steven R; Martin, Seth S; Blaha, Michael J; Michos, Erin D

2014-01-01

322

Single step reconstitution of multifunctional high-density lipoprotein-derived nanomaterials using microfluidics.  

PubMed

High-density lipoprotein (HDL) is a natural nanoparticle that transports peripheral cholesterol to the liver. Reconstituted high-density lipoprotein (rHDL) exhibits antiatherothrombotic properties and is being considered as a natural treatment for cardiovascular diseases. Furthermore, HDL nanoparticle platforms have been created for targeted delivery of therapeutic and diagnostic agents. The current methods for HDL reconstitution involve lengthy procedures that are challenging to scale up. A central need in the synthesis of rHDL, and multifunctional nanomaterials in general, is to establish large-scale production of reproducible and homogeneous batches in a simple and efficient fashion. Here, we present a large-scale microfluidics-based manufacturing method for single-step synthesis of HDL-mimicking nanomaterials (?HDL). ?HDL is shown to have the same properties (e.g., size, morphology, bioactivity) as conventionally reconstituted HDL and native HDL. In addition, we were able to incorporate simvastatin (a hydrophobic drug) into ?HDL, as well as gold, iron oxide, quantum dot nanocrystals or fluorophores to enable its detection by computed tomography (CT), magnetic resonance imaging (MRI), or fluorescence microscopy, respectively. Our approach may contribute to effective development and optimization of lipoprotein-based nanomaterials for medical imaging and drug delivery. PMID:24079940

Kim, YongTae; Fay, Francois; Cormode, David P; Sanchez-Gaytan, Brenda L; Tang, Jun; Hennessy, Elizabeth J; Ma, Mingming; Moore, Kathryn; Farokhzad, Omid C; Fisher, Edward Allen; Mulder, Willem J M; Langer, Robert; Fayad, Zahi A

2013-11-26

323

Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage  

SciTech Connect

The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

1991-12-01

324

The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys  

PubMed Central

Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL–sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL–sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-?-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

Dong, Qiao-Xiang; Rodenburg, Sarah E; Hill, Dana; VandeVoort, Catherine A

2011-01-01

325

Contribution of High Plasma Triglycerides and Low High-Density Lipoprotein Cholesterol to Residual Risk of Coronary Heart Disease After Establishment of Low-Density Lipoprotein Cholesterol Control  

PubMed Central

To determine the relative contributions of triglycerides (TGs) and high-density lipoprotein (HDL) cholesterol in the residual risk of coronary heart disease (CHD) after the reduction of low-density lipoprotein (LDL) cholesterol to guideline-recommended levels, we conducted a hospital-based, case-control study with optimal matching in the strata of LDL cholesterol, gender, ethnicity, and age. The 170 cases and 175 controls were patients at Brigham and Women's Hospital (Boston, Massachusetts) from 2005 to 2008 who had an LDL cholesterol level <130 mg/dl. The cases had incident CHD, and the controls had diagnoses unrelated to CHD. The 170 cases and 175 controls had a mean LDL cholesterol level of 73 and 87 mg/dl, respectively. The association between TG and HDL cholesterol levels and CHD risk was assessed using conditional and unconditional logistic regression analysis. The models investigated accommodated the possibility of an interaction between lipid factors. The odds of CHD increased by approximately 20% per 23-mg/dl increase in TGs and decreased by approximately 40% per 7.5-mg/dl decrease in HDL cholesterol. High TGs and low HDL cholesterol interacted synergistically to increase the odds ratio to 10 for the combined greatest TG (?190 mg/dl) and lowest HDL cholesterol quintiles (<30 mg/dl). High TG levels were more strongly associated with CHD when the HDL cholesterol was low than average or high; and low HDL cholesterol levels were more strongly associated with CHD when the TGs were high. TGs and HDL cholesterol were associated with CHD in patients with a LDL cholesterol level of ?70 mg/dl, with a risk similar to, or greater than, those in the total group. In conclusion, high TG and low HDL cholesterol levels contribute strongly and synergistically to CHD when LDL cholesterol is well controlled. Thus, high TGs might have greater importance in patients with optimal rather than greater LDL cholesterol concentrations.

Carey, Vincent J.; Bishop, Louise; Laranjo, Nancy; Harshfield, Benjamin J.; Kwiat, Carolyn; Sacks, Frank M.

2014-01-01

326

The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy  

PubMed Central

Apolipoprotein?A-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues?99–163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues?6–98 and 164–238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a ?-strand (residues?149–157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods.

Oda, Michael N; Budamagunta, Madhu S; Borja, Mark S; Petrlova, Jitka; Voss, John C; Lagerstedt, Jens O

2013-01-01

327

Beneficial effect of gemfibrozil on the chemical composition and oxidative susceptibility of low density lipoprotein: a randomized, double-blind, placebo-controlled study.  

PubMed

Previous reports have shown that administration of fibrates can reduce coronary events and also improve plasma lipid levels. Oxidative modification of low density lipoprotein has been implicated in the pathogenesis of atherosclerosis, and the resistance of low density lipoprotein (LDL) to in vitro oxidation has been found to be correlated with the extent of atherosclerosis. We performed a double-blind, placebo-controlled intervention trial to establish whether gemfibrozil could improve resistance of LDL to oxidation in patients with hyperlipidemia. Patients were randomly assigned to treatment with gemfibrozil (450 mg, twice a day, n = 10) or placebo (n = 9) for 8 weeks. Blood samples were obtained after an overnight (12 h) fast. Gemfibrozil administration significantly reduced total plasma cholesterol and triglyceride levels and changed the LDL from small, dense particles (pattern B, < or = 25.5 nm) to larger, more buoyant particles (pattern A, > 25.5 nm). Gemfibrozil significantly increased the lag time of LDL oxidation in vitro by 18.2% from 45.5 +/- 8.0 min at week 0 to 53.4 +/- 11.4 min at week 8, but did not change LDL vitamin E and beta-carotene concentrations. Surprisingly, gemfibrozil significantly decreased LDL lipid peroxides by -33.1% and increased the LDL vitamin E/lipid peroxide ratio by 67.6% from 1.3 +/- 0.5 at week 0 to 2.1 +/- 0.9 at week 8. These results demonstrate that gemfibrozil treatment can render LDL less susceptible to oxidative modification while reducing plasma cholesterol and triglyceride and improving LDL subclass pattern. This antioxidative effect of gemfibrozil on LDL may be one of the factors which could delay the progression of atherosclerosis. PMID:9699906

Yoshida, H; Ishikawa, T; Ayaori, M; Shige, H; Ito, T; Suzukawa, M; Nakamura, H

1998-07-01

328

Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies  

PubMed Central

Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNF? and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

Vanhamme, Luc; Roumeguere, Thierry; Zouaoui Boudjeltia, Karim

2013-01-01

329

Postprandial Changes in High Density Lipoproteins in Rats Subjected to Gavage Administration of Virgin Olive Oil  

PubMed Central

Background and Aims The present study was designed to verify the influence of acute fat loading on high density lipoprotein (HDL) composition, and the involvement of liver and different segments of small intestine in the changes observed. Methods and Results To address these issues, rats were administered a bolus of 5-ml of extra-virgin olive oil and sacrificed 4 and 8 hours after feeding. In these animals, lipoproteins were analyzed and gene expressions of apolipoprotein and HDL enzymes were assessed in duodenum, jejunum, ileum and liver. Using this experimental design, total plasma and HDL phospholipids increased at the 8-hour-time-point due to increased sphingomyelin content. An increase in apolipoprotein A4 was also observed mainly in lipid-poor HDL. Increased expression of intestinal Apoa1, Apoa4 and Sgms1 mRNA was accompanied by hepatic decreases in the first two genes in liver. Hepatic expression of Abcg1, Apoa1bp, Apoa2, Apoe, Ptlp, Pon1 and Scarb1 decreased significantly following fat gavage, while no changes were observed for Abca1, Lcat or Pla2g7. Significant associations were also noted for hepatic expression of apolipoproteins and Pon1. Manipulation of postprandial triglycerides using an inhibitor of microsomal transfer protein -CP-346086- or of lipoprotein lipase –tyloxapol- did not influence hepatic expression of Apoa1 or Apoa4 mRNA. Conclusion All these data indicate that dietary fat modifies the phospholipid composition of rat HDL, suggesting a mechanism of down-regulation of hepatic HDL when intestine is the main source of those particles and a coordinated regulation of hepatic components of these lipoproteins at the mRNA level, independently of plasma postprandial triglycerides.

Martinez-Beamonte, Roberto; Navarro, Maria A.; Acin, Sergio; Guillen, Natalia; Barranquero, Cristina; Arnal, Carmen; Surra, Joaquin; Osada, Jesus

2013-01-01

330

Oleic acid rich diet protects against the oxidative modification of high density lipoprotein.  

PubMed

Oxidative modifications of lipoproteins could contribute to the development of atherosclerosis, but the influence of dietary fats on high density lipoprotein (HDL) oxidative modification is unknown. This study was designed to determine whether a diet rich in oleic acid could modulate the oxidative modification of HDL3. Twenty two healthy men were randomly placed on a 32-wk crossover study of an oleic acid rich diet supplied by a variant of sunflower oil vs a linoleic acid rich diet provided by conventional sunflower oil. Plasma HDL3 obtained after the diet rich in oleic acid showed a significantly higher oleic acid content in the phospholipid than lipoprotein isolated after the linoleic acid rich diet. HDL3 isolated after the oleic acid rich diet had lower values of thiobarbituric acid reactive substances (TBARS) than HDL3 obtained after the linoleic acid rich diet both for native (mean +/- SE; 0.24 +/- 0.02 vs 0.42 +/- 0.08 nmol MDA/mg protein; p < 0.01) and copper oxidized HDL3 (0.75 +/- 0.06 vs 0.95 +/- 0.07 nmol MDA/mg protein; p < 0.01). Indeed, TBARS for native HDL3 were negatively correlated with the oleic acid to linoleic acid ratio and positively with the percentage of linoleic acid in their phospholipids. Interestingly, HDL3 after both diets had similar antioxidant vitamins A and E content. HDL3 overall composition and fluidity were similar after the two diets. Moreover, HDL3 obtained after both diets produced identical [3H] free cholesterol efflux from human monocyte-derived macrophages (29%) and fibroblasts (26%). In conclusion, HDL3 rich in oleic acid was less easily oxidized regardless of the content of antioxidants such as vitamins A and E. Therefore, dietary monounsaturated fatty acid prevent the oxidative modification of lipoproteins. PMID:9034243

Solà, R; La Ville, A E; Richard, J L; Motta, C; Bargalló, M T; Girona, J; Masana, L; Jacotot, B

1997-01-01

331

Comparison of gemfibrozil versus simvastatin in familial combined hyperlipidemia and effects on apolipoprotein-B-containing lipoproteins, low-density lipoprotein subfraction profile, and low-density lipoprotein oxidizability.  

PubMed

We evaluated in a double-blind, placebo-controlled, randomized trial of 45 well-defined patients with familial combined hyperlipidemia, the effect of gemfibrozil (1,200 mg/day) or simvastatin (20 mg/day) on apolipoprotein-B (apo-B)-containing lipoproteins, low-density lipoprotein (LDL) subfraction profile, and LDL oxidizability. Although both drugs reduced plasma cholesterol and triglyceride concentrations, gemfibrozil reduced plasma triglycerides more effectively and simvastatin reduced plasma cholesterol more effectively. LDL cholesterol was reduced with simvastatin. With both drugs, total serum apo-B concentration decreased. With gemfibrozil, this was due to an exclusive reduction (-46%) of very low/intermediate-density lipoprotein (VLDL + IDL) apo-B, whereas simvastatin decreased apo-B in both VLDL + IDL and LDL (34% and 15%, respectively). Initially, a dense LDL subfraction profile was present in all patients. The decrease in LDL cholesterol with simvastatin was due to a decrease in all isolated LDL subfractions except LDL2; gemfibrozil increased LDL1 and LDL2 cholesterol (p = 0.001) and reduced LDL4 cholesterol, resulting in a more buoyant LDL subfraction profile compared with simvastatin. In both groups, a predominance of small dense LDL remained despite therapy. LDL fatty acid composition showed a shift from oleic acid to linoleic acid after gemfibrozil; arachidonic acid increased after simvastatin. Vitamin E was lower after gemfibrozil. In the measurements of LDL oxidation, only the oxidation rate was significantly reduced with simvastatin. Thus, quantitative and qualitative changes of LDL cholesterol had only a small effect on total in vitro LDL oxidizability in this population with familial combined hyperlipidemia. PMID:7856526

Bredie, S J; de Bruin, T W; Demacker, P N; Kastelein, J J; Stalenhoef, A F

1995-02-15

332

Lipoprotein-associated lysolipids are differentially involved in high-density lipoprotein- and its oxidized form-induced neurite remodeling in PC12 cells.  

PubMed

Oxidatively damaged proteins and lipid peroxidation products have been shown to accumulate in the brain of neurodegenerative diseases, such as Alzheimer's disease and multiple sclerosis, and oxidized lipoprotein is considered to be toxic and neurodegenerative. However, the role of lipoprotein and its oxidized form in neurite remodeling has not been well understood. In the present study, we have aimed to clarify whether and, if so, how high-density lipoprotein (HDL) and oxidized HDL (oxHDL) affect neuritogenesis. In the presence of nerve growth factor, exposure of PC12 cells to either HDL or oxHDL induces a rapid neurite retraction, which is followed by re-outgrowth of neurites in either case; however, oxHDL-treated cells exhibit much longer outgrowths than do basal and HDL-treated cells. Thus, processes in the morphological changes of neuronal cells after lipoprotein treatment are composed of two phases: the reversible retraction phase and the extension phase. Characterization of the active fractions of lipids and experiments with desensitization and knockdown of receptors have indicated that the reversible retraction phase involves mainly sphingosine 1-phosphate for HDL and lysophosphatidic acid for oxHDL. The change in the components responsible for the retraction response is comparable with the change in sphingosine 1-phosphate and lysophosphatidic acid contents by the oxidation of HDL. In the extension phase, lysophosphatidylcholine, which is increased by the oxidation of HDL, may play a stimulatory role in neurite outgrowth. We conclude that lipoprotein and its oxidized form differentially regulate neuritogenesis through lipoprotein-associated lysolipid molecules. PMID:24589770

Sato, Koichi; Tobo, Masayuki; Mogi, Chihiro; Murata, Naoya; Kotake, Mie; Kuwabara, Atsushi; Im, Dong-Soon; Okajima, Fumikazu

2014-03-01

333

Circulating oxidized low-density lipoprotein and paraoxonase activity in preeclampsia.  

PubMed

Preeclampsia is one of the most frequent complications of pregnancy, however, little is known about its etiology. The objective of this study was to investigate the association of oxidized low-density lipoprotein (oxLDL) and paraoxonase (PON1) activity in women with either preeclampsia or normotensive (NT) pregnancy. The study groups included 41 pregnant women with preeclampsia and 33 normotensive pregnant women. In all patients maternal serum total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs) were measured using enzymatic methods. Serum PON1 activities and malondialdehyde (MDA) concentrations were measured by spectrophotometric methods, and oxLDL was measured by enzyme-linked immunoassay (ELISA). Serum concentrations of lipid parameters (TC, LDL, VLDL, and TGs) were significantly higher in preeclampsia compared with NT controls (p < 0.001, p < 0.05, p < 0.05, and p < 0.001, respectively). Serum concentrations of MDA and oxLDL were significantly higher, while PON1 activity was significantly lower in preeclampsia compared with NT controls (p < 0.001, p < 0.001, and p < 0.001, respectively). A positive correlation was detected between oxLDL and MDA (r = 0.876), and a negative correlation was detected between both MDA and oxLDL and PON1 (r = -0.837 and r = -0.759, respectively). Our data demonstrate that preeclampsia is associated with increased oxLDL and decreased PON1 activity. Elevated oxidative stress, oxLDL, dyslipidemia and decreased PON1 activities may cause vascular endothelial damage and contribute to the pathophysiology of preeclampsia. PMID:16088195

Uzun, H; Benian, A; Madazli, R; Topçuo?lu, M A; Aydin, S; Albayrak, M

2005-01-01

334

Uptake of oxidized low-density lipoprotein in a THP1 cell line lacking scavenger receptor A  

Microsoft Academic Search

We previously isolated THP-1 subtype cells (sTHP-1), a cell line that expresses scanty amounts of scavenger receptor A (ScR-A) and does not undergo foam cell formation when incubated with acetylated low-density lipoprotein (Ac-LDL). In this study, we investigated the accumulation of esterified cholesterol in sTHP-1 cells incubated with oxidized LDL (Ox-LDL), a physiologically modified lipoprotein in human. While sTHP-1 cells

Ryo Sugano; Taku Yamamura; Mariko Harada-Shiba; Yasuko Miyake; Akira Yamamoto

2001-01-01

335

Biochemical Characterization of Alzheimer's Soluble Amyloid Beta Protein in Human Cerebrospinal Fluid: Association with High Density Lipoproteins  

Microsoft Academic Search

The soluble form of Alzheimer's amyloid ? protein (sA?) is associated with high density lipoproteins (HDL) in normal human plasma (BBRC,1994,205,1164–1171). Since sA? is also present in cerebrospinal fluid (CSF) and the lipoprotein pattern of CSF is different from that of plasma, it was of interest to ascertain whether the interaction of sA? with HDL also occurs in CSF. Normal

Alexei R. Koudinov; Natalia V. Koudinova; Asok Kumar; Ronald C. Beavis; Jorge Ghiso

1996-01-01

336

Plasma high density lipoprotein subgroup distribution in rats fed diets with varying amounts of sucrose and sunflower oil  

Microsoft Academic Search

The effect of varying the dietary sunflower oil\\/sucrose (SO\\/SU) ratio on rat plasma lipid concentration and lipoprotein distribution\\u000a was studied. Four groups of 10 rats were fed for 4 weeks diets with varying SO\\/SU ratios. Lipoprotein components were then\\u000a estimated in whole plasma and after cumulative density ultracentrifugation. Whole plasma triacylglycerol (TG), total cholesterol\\u000a (TC) and free cholesterol (FC) decreased

Arne T. Høstmark; Øystein Spydevold; Einar Lystad; Eva Kristensen; Ida Goffeng Bay

1982-01-01

337

Peroxisome proliferator-activated receptor promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage  

Microsoft Academic Search

Significant attention has focused on the role of low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis. However, recent advances have identified triglyceride-rich lipoproteins [e.g., very LDL (VLDL)] as independent risk predictors for this disease. We have previously demonstrated peroxisome proliferator-activated receptor (PPAR), but not PPAR, is the major nuclear VLDL sensor in the macrophage, which is a crucial component of

Chih-Hao Lee; Kihwa Kang; Isaac R. Mehl; Russell Nofsinger; William A. Alaynick; Ling-Wa Chong; John M. Rosenfeld; Ronald M. Evans

2006-01-01

338

Biological effects of native and oxidized low-density lipoproteins in cultured human retinal pigment epithelial cells  

Microsoft Academic Search

Age-related macular degeneration (AMD) and artherosclerosis share common characteristics in their pathogenesis. In this study, we investigated the effects of lipoproteins like native (n)-LDL, oxidized (ox)-LDL and high-density lipoprotein (HDL) on advanced senescence, extracellular matrix accumulation, cell loss, and transforming growth factor-beta2 (TGF-?2) expression in cultured human retinal pigment epithelial (RPE) cells. Primary human RPE cells were incubated with 10–100?g\\/ml

Alice L. Yu; Reinhard L. Lorenz; Christos Haritoglou; Anselm Kampik; Ulrich Welge-Lussen

2009-01-01

339

PlasmaHigh-DensityLipoproteinCholesterolConcentrations Determinedafter Removalof Other Lipoproteinsby Heparin\\/ ManganesePrecipitationor by Ultracentrifugation  

Microsoft Academic Search

isolated preparations of the lipoprotein are only partly precipitated under the test conditions. in the presentstudy, the procedure as applied to plasma tolerated rather wide variations in heparin and MnCI2concentrations without significant effects on theassayedvalues in severalplasma pools tested. The procedure was further tested on 129 individual samples by comparison with an ultracentrifugal method in which high-density lipoprotein-cholesterol is assumed

P. S. Bachorik; P. D. Wood; J. J. Albers; P. Steiner; M. Dempsey; K. Kuba

340

Nanocrystal core high-density lipoproteins: A multimodality contrast agent platform  

PubMed Central

High density lipoprotein (HDL), is an important natural nanoparticle that may be modified for biomedical imaging purposes. Here we developed a novel technique to create unique multimodality HDL mimicking nanoparticles by inclusion of gold, iron oxide or quantum dot nanocrystals for computed tomography, magnetic resonance and fluorescence imaging, respectively. By including additional labels in the corona of the particles, they were made multi-functional. The characterization of these nanoparticles, as well as their in vitro and in vivo behavior revealed that they closely mimic native HDL.

Cormode, David P.; Skajaa, Torjus; van Schooneveld, Matti M.; Koole, Rolf; Jarzyna, Peter; Lobatto, Mark E.; Calcagno, Claudia; Barazza, Alessandra; Gordon, Ronald E.; Zanzonico, Pat; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

2009-01-01

341

High density lipoproteins and type 2 diabetes: Emerging concepts in their relationship  

PubMed Central

Patients with type 2 diabetes mellitus (T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular (CV) disease. High density lipoproteins (HDL) are protective against atherosclerosis. Low levels of HDL cholesterol (HDL-C) independently contribute to CV risk. Patients with T2DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2DM through a decreased ? cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2DM with HDL.

Kostapanos, Michael S; Elisaf, Moses S

2014-01-01

342

Do neonates with high serum cholesterol levels have a different high density lipoprotein composition?  

Microsoft Academic Search

In order to ascertain whether the high density lipoprotein (HDL) composition of neonates with high serum cholesterol levels\\u000a (?2.59?mmol\\/l or ?100?mg\\/dl) differs from that of neonates with normal serum cholesterol levels (<2.59?mmol\\/l), 548 cord blood\\u000a samples were examined from full-term newborns of the Toledo Study (Spain) of whom no perinatal factors were known which could\\u000a alter cord blood lipid levels.

S. Bastida; S. Perea; F. J. Sánchez-Muniz

1997-01-01

343

Dusty punch cards and an eternal enigma: high-density lipoproteins and atherosclerosis.  

PubMed

Epidemiological, clinical, and experimental evidence has accumulated during the last decades suggesting that high-density lipoproteins (HDLs) may protect from atherosclerosis and its clinical consequences. However, more than 55 years after the first description of the link between HDL and heart attacks, many facets of the biochemistry, function, and clinical significance of HDL remain enigmatic. This applies particularly to the completely unexpected results that became available from some recent clinical trials of nicotinic acid and of inhibitors of cholesteryl ester transfer protein (CETP). The concept that raising HDL cholesterol by pharmacological means would decrease the risk of vascular disease has therefore been challenged. PMID:24691706

Kleber, Marcus E; Grammer, Tanja B; Kassner, Ursula; Silbernagel, Günther; März, Winfried

2014-04-01

344

Preparation and Activity Analysis of Recombinant Human High-Density Lipoprotein  

PubMed Central

Abstract Population studies have consistently shown a highly inverse correlation between plasma concentration of high-density lipoprotein and the risk of atherosclerotic cardiovascular disease in humans. High-density lipoprotein (HDL) as a therapeutic target is an intense area of ongoing investigation. Aiming to solve the shortcomings of native HDL application, we prepared recombinant human HDL (rhHDL) that contains a similar composition and has similar functions with native HDL. Six kinds of recombinant human apolipoproteins (rhapo)—rhapoA-I, rhapoA-II, rhapoA-IV, rhapoC-I, rhapoC-II, and rhapoE—were expressed in Pichia pastoris and purified with chromatography. By the facilitation of cholate, six kinds of rhapo penetrated among the phosphatidylcholine acyl chains. After purification by density-gradient centrifugation, rhHDL was acquired. Based on morphological observation, we confirmed that the micellar complexes of rhapo with phosphatidylcholine and cholesterol were prepared. We carried on comparative studies in vitro and in vivo between native HDL and rhHDL. Cellular cholesterol efflux assays showed that rhHDL could promote the efflux of excess cholesterol from macrophages. Furthermore, rhHDL has similar effects with native HDL on the blood lipid metabolism in hyperlipidemic mice. In conclusion, rhHDL has similar effects on antiatherosclerosis with native HDL through reverse cholesterol transport, antioxidative, and antithrombotic properties. It could be used as a therapeutic HDL-replacement agent.

Su, Manman; Chang, Weiqin; Shi, Kaiyao; Wang, Dingding; Wang, Mingxing; Yan, Weiqun

2012-01-01

345

Gradient gel electrophoretic separation of LDL and HDL subclasses on BioRad Mini Protean II and size phenotyping in healthy Macedonians  

Microsoft Academic Search

Background: Lipoprotein subclass determinations provide a more detailed reflection of lipoprotein metabolism and an accurate prediction for risk of cardiovascular disease. Gradient gel electrophoresis for lipoprotein separation on Pharmacia electrophoretic apparatus has been most commonly used for many years. Methods: In this paper, we describe a new method for separating LDL and HDL subclasses by nondenaturing polyacrylamide gradient (3–31%) gel

Sonja B Alabakovska; Bojana B Todorova; Danica D Labudovic; Katerina N Tosheska

2002-01-01

346

Altered lipoprotein metabolism in chronic inflammatory states: proinflammatory high-density lipoprotein and accelerated atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis  

PubMed Central

In this review, the authors discuss the formation and structure of high-density lipoproteins (HDLs) and how those particles are altered in inflammatory or stress states to lose their capacity for reverse cholesterol transport and for antioxidant activity. In addition, abnormal HDLs can become proinflammatory (piHDLs) and actually contribute to oxidative damage. The assay by which piHDLs are identified involves studying the ability of test HDLs to prevent oxidation of low-density lipoproteins. Finally, the authors discuss the potential role of piHDLs (found in some 45% of patients with systemic lupus erythematosus and 20% of patients with rheumatoid arthritis) in the accelerated atherosclerosis associated with some chronic rheumatic diseases.

Hahn, Bevra H; Grossman, Jennifer; Ansell, Benjamin J; Skaggs, Brian J; McMahon, Maureen

2008-01-01

347

Effects of Statins on High-Density Lipoproteins: A Potential Contribution to Cardiovascular Benefit  

PubMed Central

Purpose The objective was to systematically review clinical trial data on the effects of statins on high-density lipoproteins (HDL) and to examine the possibility that this provides cardiovascular benefits in addition to those derived from reductions in low-density lipoproteins (LDL). Methods The PubMed database was searched for publications describing clinical trials of atorvastatin, pravastatin, rosuvastatin, and simvastatin. On the basis of predefined criteria, 103 were selected for review. Results Compared with placebo, statins raise HDL, measured as HDL-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I); these elevations are maintained in the long-term. In hypercholesterolemia, HDL-C is raised by approximately 4% to 10%. The percentage changes are greater in patients with low baseline levels, including those with the common combination of high triglycerides (TG) and low HDL-C. These effects do not appear to be dose-related although there is evidence that, with the exception of atorvastatin, the changes in HDL-C are proportional to reductions in apo B-containing lipoproteins. The most likely explanation is a reduced rate of cholesteryl ester transfer protein (CETP)-mediated flow of cholesterol from HDL. There is some evidence that the statin effects on HDL reduce progression of atherosclerosis and risk of cardiovascular disease independently of reductions in LDL. Conclusion Statins cause modest increases in HDL-C and apo A-I probably mediated by reductions in CETP activity. It is plausible that such changes independently contribute to the cardiovascular benefits of the statin class but more studies are needed to further explore this possibility.

Jones, Peter

2008-01-01

348

Proteomic analysis of proteins eliminated by low-density lipoprotein apheresis.  

PubMed

Low-density lipoprotein apheresis (LDL-A) treatment has been shown to decrease serum LDL cholesterol levels and prevent cardiovascular events in homozygous patients with familial hypercholesterolemia. Recently, LDL-A treatment has been suggested to have beneficial effects beyond the removal of LDL particles. In this study, to clarify the preventive effects of LDL-A treatment on atherosclerosis, the waste fluid from the adsorption columns was analyzed. The waste fluid of LDL adsorption columns was analyzed by two-dimensional electrophoresis followed by mass spectrometry. Serum concentrations of the newly identified proteins before and after LDL-A treatment were measured by enzyme-linked immunosorbent assay. We identified 48 kinds of proteins in the waste fluid of LDL adsorption columns, including coagulation factors, thrombogenic factors, complement factors, inflammatory factors and adhesion molecules. In addition to the proteins that were reported to be removed by LDL-A treatment, we newly identified several proteins that have some significant roles in the development of atherosclerosis, including vitronectin and apolipoprotein C-III (Apo C-III). The serum levels of vitronectin and Apo C-III decreased by 82.4% and 54.8%, respectively, after a single LDL-A treatment. While Apo C-III was removed with very low-density lipoprotein (VLDL) and LDL, vitronectin was removed without association with lipoproteins. The removal of proteins observed in the waste fluid has a certain impact on their serum levels, and this may be related to the efficacy of LDL-A treatment. Proteomic analysis of the waste fluid of LDL adsorption columns may provide a rational means of assessing the effects of LDL-A treatment. PMID:24499090

Yuasa, Yumiko; Osaki, Tsukasa; Makino, Hisashi; Iwamoto, Noriyuki; Kishimoto, Ichiro; Usami, Makoto; Minamino, Naoto; Harada-Shiba, Mariko

2014-02-01

349

Significance of high density lipoprotein-cholesterol in cardiovascular risk prevention: recommendations of the HDL Forum.  

PubMed

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome. PMID:15449972

Ascaso, Juan F; Fernández-Cruz, Arturo; González Santos, Pedro; Hernández Mijares, Antonio; Mangas Rojas, Alipio; Millán, Jesus; Felipe Pallardo, Luis; Pedro-Botet, Juan; Pérez-Jiménez, Francisco; Pía, Gonzalo; Pintó, Xavier; Plaza, Ignacio; Rubiés-Prat, Juan

2004-01-01

350

Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population.  

PubMed

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL?C) and total cholesterol (TC) to HDL?C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL?C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ? 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL?C ratio, TC/HDL?C ratio and low ABI. Results: The TG/HDL?C ratios for those with ABI > 0.9 and ABI ? 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL?C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL?C ratio and TC/HDL?C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL?C ratio and TC/HDL?C ratio, respectively. Non-linear relationships were detected between TG/HDL?C ratio and TC/HDL?C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL?C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL?C, and LDL-C. TC/HDL?C might be considered as a potential biomarker for early peripheral arterial disease screening. PMID:24797050

Zhan, Yiqiang; Yu, Jinming; Ding, Rongjing; Sun, Yihong; Hu, Dayi

2014-05-01

351

Dietary Olive Oil Reduces Low-Density Lipoprotein Uptake by Macrophages and Decreases the Susceptibility of the Lipoprotein to Undergo Lipid Peroxidation  

Microsoft Academic Search

Low-density lipoprotein (LDL) oxidation and macrophage cholesterol accumulation are both involved in atherogenesis. Recently it was shown that feeding rabbits or humans with an oleic-acid-rich diet reduced the susceptibility of their LDL to in vitro oxidation. Since olive oil is highly enriched with oleic acid, we tested the effect of olive oil supplementation (50 g\\/day) to the diet of 10

Michael Aviram; Kassem Eias

1993-01-01

352

Reduced adipose tissue lipoprotein lipase responses, postprandial lipemia, and low high-density lipoprotein-2 subspecies levels in older athletes with silent myocardial ischemia.  

PubMed

Healthy older (64 +/- 1 years, mean +/- SEM) athletic (maximal oxygen consumption [VO2max] > 40 mL/kg/min) normocholesterolemic men with no prior history of coronary artery disease (CAD) were recruited for cardiovascular and metabolic studies. Thirty-three percent had asymptomatic exercise-induced ST segment depression on their exercise electrocardiogram (ECG), consistent with silent myocardial ischemia (SI). We hypothesized that abnormalities in high-density lipoprotein (HDL) and postprandial triglyceride (TG) metabolism may increase their risk for CAD. Compared with 12 nonischemic controls of comparable age, percent body fat, and VO2max, the 13 men with SI had decreased fasting HDL cholesterol ([HDL-C] 41 +/- 2 v 50 +/- 2 mg/dL, P < .001) and %HDL2b subspecies levels as measured by gradient gel electrophoresis (22 +/- 2 v 34 +/- 3, P < .001). Fasting plasma TG and low-density lipoprotein cholesterol (LDL-C) levels were the same in both groups. Although plasma glucose levels during an oral glucose tolerance test (OGTT) were similar in both groups, the total insulin area was higher in men with SI (P < .05). After consumption of a standard high-fat meal (680 kcal/m2 body surface area of a formula in which 86% of the calories were derived from fat), postprandial plasma TG, chylomicron-TG, and very-low-density lipoprotein (VLDL)-TG levels and postprandial areas were higher in men with SI (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8121301

Katzel, L I; Busby-Whitehead, M J; Rogus, E M; Krauss, R M; Goldberg, A P

1994-02-01

353

Standardization of a Method to Evaluate the Antioxidant Capacity of High-Density Lipoproteins  

PubMed Central

Background: A method to evaluate the antioxidant capacity of high-density lipoprotein (HDL) was developed and standardized. Methods: This method measure conjugated diene (CD) formation and electrophoretic mobility of low-density lipoprotein (LDL) in agarose gels in the presence and absence of HDL. HDL was isolated from 1 mL of plasma within 24 hours and oxidation assays were performed within 6 hours. Oxidation was induced by adding CuSO4. The lag phase increase in CD kinetics and the inhibition of electrophoretic mobility were defined as the HDL antioxidant capacity. Results: The optimal conditions for the CD assay were 2.5 ?M CuSO4, LDL at 0.1 g apoB/L, HDL at 0.1 g apoA-I/L, at 37°C and for 3h 50 min. Agarose electrophoresis at 100 V, at 4°C for 50 min was then performed immediately. CD formation variability was 21.1% for inter-assay CV and 12.7% for intra-assay CV. Electrophoretic mobility was 26.5% for inter-assay CV and 2.4% for intra-assay CV. Correlation analysis showed a significant association between the antioxidant capacity of HDL and its neutral/polar lipid ratio. Conclusions: The method herein described measures of the HDL antioxidant capacity in a reproducible and rapid manner that can be applied to a relatively high number of samples.

de Juan-Franco, Elena; Perez, Antonio; Ribas, Vicent; Sanchez-Hernandez, Juan Antonio; Blanco-Vaca, Francisco; Ordonez-Llanos, Jordi; Sanchez-Quesada, Jose Luis

2009-01-01

354

Novel Changes in Discoidal High Density Lipoprotein Morphology: A Molecular Dynamics Study  

PubMed Central

ApoA-I is a uniquely flexible lipid-scavenging protein capable of incorporating phospholipids into stable particles. Here we report molecular dynamics simulations on a series of progressively smaller discoidal high density lipoprotein particles produced by incremental removal of palmitoyloleoylphosphatidylcholine via four different pathways. The starting model contained 160 palmitoyloleoylphosphatidylcholines and a belt of two antiparallel amphipathic helical lipid-associating domains of apolipoprotein (apo) A-I. The results are particularly compelling. After a few nanoseconds of molecular dynamics simulation, independent of the starting particle and method of size reduction, all simulated double belts of the four lipidated apoA-I particles have helical domains that impressively approximate the x-ray crystal structure of lipid-free apoA-I, particularly between residues 88 and 186. These results provide atomic resolution models for two of the particles produced by in vitro reconstitution of nascent high density lipoprotein particles. These particles, measuring 95 Å and 78 Å by nondenaturing gradient gel electrophoresis, correspond in composition and in size/shape (by negative stain electron microscopy) to the simulated particles with molar ratios of 100:2 and 50:2, respectively. The lipids of the 100:2 particle family form minimal surfaces at their monolayer-monolayer interface, whereas the 50:2 particle family displays a lipid pocket capable of binding a dynamic range of phospholipid molecules.

Catte, Andrea; Patterson, James C.; Jones, Martin K.; Jerome, W. Gray; Bashtovyy, Denys; Su, Zhengchang; Gu, Feifei; Chen, Jianguo; Aliste, Marcela P.; Harvey, Stephen C.; Li, Ling; Weinstein, Gilbert; Segrest, Jere P.

2006-01-01

355

High-density lipoprotein cholesterol targeting for novel drug discovery: where have we gone wrong?  

PubMed

Lowering low-density lipoprotein-cholesterol (LDL-C) is an effective strategy to reduce cardiovascular risk. However, a significant residual risk remains in statin-treated patients. High-density lipoprotein cholesterol (HDL-C) is a strong, independent and inverse predictor of cardiovascular risk in many epidemiologic studies and has, therefore, emerged as a potential novel therapeutic target for addressing this substantial residual risk. Nevertheless, the failure of cholesteryl ester transfer protein (CETP) inhibitors and niacin in clinical trials has generated considerable speculation about the beneficial effects of HDL. Experimental studies have identified several HDL cardioprotective functions, including enhancement of macrophage reverse cholesterol transport and endothelial function and its antioxidant, anti-inflammatory and anti-thrombotic properties. Furthermore, HDL is highly heterogeneous and the atheroprotective functions of the different HDL subpopulations are not completely understood. Current available data indicate that increased HDL-C levels do not always correlate with enhanced HDL functions and, therefore, should not be considered a biomarker of HDL functionality. The clinical application of the novel HDL-based therapeutic approaches requires the development of validated and reproducible measures of key HDL functions. PMID:24328789

Escolà-Gil, Joan Carles; Cedó, Lídia; Blanco-Vaca, Francisco

2014-02-01

356

Meta-Analysis of Low Density Lipoprotein Receptor (LDLR) rs2228671 Polymorphism and Coronary Heart Disease  

PubMed Central

Low density lipoprotein receptor (LDLR) can regulate cholesterol metabolism by removing the excess low density lipoprotein cholesterol (LDL-C) in blood. Since cholesterol metabolism is often disrupted in coronary heart disease (CHD), LDLR as a candidate gene of CHD has been intensively studied. The goal of our study is to evaluate the overall contribution of LDLR rs2228671 polymorphism to the risk of CHD by combining the genotyping data from multiple case-control studies. Our meta-analysis is involved with 8 case-control studies among 7588 cases and 9711 controls to test the association between LDLR rs2228671 polymorphism and CHD. In addition, we performed a case-control study of LDLR rs2228671 polymorphism with the risk of CHD in Chinese population. Our meta-analysis showed that rs2228671-T allele was significantly associated with a reduced risk of CHD (P = 0.0005, odds ratio (OR)?=?0.83, and 95% confidence interval (95% CI)?=?0.75–0.92). However, rs2228671-T allele frequency was rare (1%) and was not associated with CHD in Han Chinese (P = 0.49), suggesting an ethnic difference of LDLR rs2228671 polymorphism. Meta-analysis has established rs2228671 as a protective factor of CHD in Europeans. The lack of association in Chinese reflects an ethnic difference of this genetic variant between Chinese and European populations.

Ye, Huadan; Zhao, Qianlei; Huang, Yi; Wang, Lingyan; Liu, Haibo; Wang, Chunming; Dai, Dongjun; Xu, Leiting; Ye, Meng; Duan, Shiwei

2014-01-01

357

Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus  

PubMed Central

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of ?-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.

Bays, Harold E

2014-01-01

358

Low Density Lipoprotein-Containing Circulating Immune Complexes: Role in Atherosclerosis and Diagnostic Value  

PubMed Central

It has been suggested that low density lipoprotein-containing circulating immune complexes (LDL-CIC) play a role in atherogenesis and are involved in the formation of early atherosclerotic lesion. These complexes, as well as anti-LDL autoantibodies, have been found in the blood and in the atherosclerotic lesions of patients with different cardiovascular diseases, as well as in the blood of animals with experimental atherosclerosis. It can be suggested that the presence of anti-LDL antibodies in the blood is a result of immune response induced by lipoprotein modification. LDL-CIC differs from native LDL in many aspects. It has much lower sialic acid content, smaller diameter, and higher density and is more electronegative than native LDL. Fraction of LDL-CICs is fundamental to the serum atherogenicity manifested at the cellular level. LDL-CIC, unlike native LDL, is able to induce intracellular accumulation of neutral lipids, especially esterified cholesterol, in cells cultured from uninvolved human aortic intima and in macrophage cultures. After removal of LDL-CIC, the CHD patient's sera lose their atherogenic properties. Titer of LDL-CIC in blood serum significantly correlates with progression of atherosclerosis in human in vivo and has the highest diagnostic value among other measured serum lipid parameters. Elevated CIC-cholesterol might well be a possible risk factor of coronary atherosclerosis.

Sobenin, Igor A.; Salonen, Jukka T.; Zhelankin, Andrey V.; Melnichenko, Alexandra A.; Kaikkonen, Jari; Bobryshev, Yuri V.; Orekhov, Alexander N.

2014-01-01

359

Plasma thiols inhibit hemin-dependent oxidation of human low-density lipoprotein.  

PubMed

Oxidative modification of human low-density lipoprotein (LDL) renders it atherogenic. Previous studies demonstrated that plasma thiols promote oxidation of LDL by free ferric iron (Fe3+). The current study investigated effects of plasma thiols on oxidation of LDL by hemin, a physiological Fe3+-protoporphyrin IX complex thought to be capable of initiating LDL oxidation in vivo. In contrast to free Fe3+ which is incapable of oxidizing LDL in the absence of an exogenous reductant, hemin readily promoted LDL oxidation. During incubation of LDL (0.2 mg of protein/ml) with hemin (10 microM) at 37 degrees C for 6 h, thiobarbituric acid-reactive substances (TBARS), a marker of lipid oxidation, increased from 0.3 (+/-0.1) nmol/mg of LDL protein to a maximal concentration of 45.8 (+/-5.2) nmol/mg of LDL protein. Under the same experimental conditions, lipid-conjugated dienes, another marker of lipid oxidation, increased from non-detectable to near-maximal levels of 78-187 nmol/mg of LDL protein, and lipoprotein polyunsaturated fatty acyl-containing cholesteryl ester content decreased to 15-36% of that present in native (i.e. unoxidized) LDL. Continued incubation of LDL with hemin for up to 24 h resulted in no further significant alterations in lipoprotein levels of TBARS, lipid-conjugated dienes, and cholesteryl esters. In addition to these chemical modifications indicative of lipoprotein oxidation, agarose gel electrophoretic analysis indicated that exposure of LDL to hemin resulted in conversion of the lipoprotein to an atherogenic form as evidenced by its increased anodic electrophoretic mobility. Addition of physiological concentrations of plasma thiols (either cysteine, homocysteine or reduced glutathione; 1-100 microM, each) inhibited hemin-mediated oxidation of LDL. Thus, whereas the maximal TBARS concentration was achieved following 6 h of incubation of LDL with hemin alone, addition of thiol extended the time required to attain maximal TBARS concentration to > or = 12 h. Similar antioxidant effects of thiols on formation of lipid-conjugated dienes, loss of cholesteryl esters, and lipoprotein anodic electrophoretic mobility were also observed. However, all thiols were not equally effective at inhibiting hemin-dependent LDL oxidation. Thus, whereas reduced glutathione was most effective at inhibiting hemin-dependent LDL oxidation, an intermediate effect was observed for homocysteine, and cysteine was least effective. The inhibition of hemin-mediated LDL oxidation by plasma thiols reported here confirms a previous observation that, under certain conditions, thiols can function as antioxidants, but contrasts with the previously documented pro-oxidant effect of the same thiols on oxidation of LDL by free Fe3+. These contrasting effects of plasma thiols on hemin- and free Fe3+-mediated LDL oxidation indicate that, in vivo, the ability of thiols to function as either anti- or pro-oxidants during LDL oxidation may, at least in part, be determined by the type of oxidant stress to which the lipoprotein is exposed. PMID:10802245

Lynch, S M; Campione, A L; Moore, M K

2000-05-01

360

Passage of Low-density Lipoproteins Through Bruch's Membrane and Choroid  

PubMed Central

Plasma lipoproteins are thought to transport cholesterol, vitamins and carotenoids to the retinal pigment epithelium (RPE) for ultimate use by the photoreceptors. However, to reach the RPE, these lipoprotein particles must cross Bruch’s membrane. We examined the reflection coefficient of Bruch’s membrane (BrM) to low-density lipoprotein (LDL). Bruch’s membrane and choroid were removed from 47 bovine eyes. Specimens were placed in a Ussing chamber and perfused with phosphate-buffered saline (PBS) with (31 specimens) or without (16 specimens) fluorescent low-density lipoproteins (DiI-LDL). The hydraulic conductivity of the tissue was determined for both calf and cow eyes. In the perfusions with DiI-LDL, the fluorescence intensity emitted by DiI-LDL in the efflux was measured and the reflection coefficient of BrM/choroid preparations to DiI-LDL determined. Leakage tests were done to confirm tissue integrity. Several specimens were examined using scanning electron microscopy (SEM) to examine tissue integrity before and after perfusion. Leak testing confirmed that BrM was intact both before and after perfusion. The average hydraulic conductivity of BrM/choroid perfusion of calf eyes with PBS alone was 1.42 ± 0.55 ×10?9 m/s/Pa (mean ± SD, n = 11). The average hydraulic conductivity of the cow eyes was 4.94 ± 1.48 ×10?10 m/s/Pa (n = 5), nearly a 3-fold decrease with age. While the flow rate remained constant during the PBS perfusions, it decreased as a function of time during perfusion with DiI-LDLs. Our major finding was of fluorescence in the effluent collected in all perfusions with DiI-LDLs, demonstrating passage of LDL through the tissue. The average reflection coefficient of calf BrM/choroid preparations to DiI-LDL was 0.58 ± 0.25 (n = 23); a similar distribution of reflection coefficients was seen in tissue from cow eyes (0.51 ± 0.33, n = 8). Our data suggested that the DiI-LDL was modestly hindered and/or captured by the tissue. This might explain the progressive decrease of hydraulic conductivity with continued perfusion of DiI-LDL.

Cankova, Zdravka; Huang, Jiahn-Dar; Kruth, Howard S.; Johnson, Mark

2011-01-01

361

Hepatitis C virus stimulates low-density lipoprotein receptor expression to facilitate viral propagation.  

PubMed

Lipids play a crucial role in multiple aspects of hepatitis C virus (HCV) life cycle. HCV modulates host lipid metabolism to enrich the intracellular milieu with lipids to facilitate its proliferation. However, very little is known about the influence of HCV on lipid uptake from bloodstream. Low-density lipoprotein receptor (LDLR) is involved in uptake of cholesterol rich low-density lipoprotein (LDL) particles from the bloodstream. The association of HCV particles with lipoproteins implicates their role in HCV entry; however, the precise role of LDLR in HCV entry still remains controversial. Here, we investigate the effect of HCV infection on LDLR expression and the underlying mechanism(s) involved. We demonstrate that HCV stimulates LDLR expression in both HCV-infected Huh7 cells and in liver tissue from chronic hepatitis C patients. Fluorescence activated cell sorting and immunofluorescence analysis revealed enhanced cell surface and total expression of LDLR in HCV-infected cells. Increased LDLR expression resulted in the enhanced uptake of lipoprotein particles by HCV-infected cells. Analysis of LDLR gene promoter identified a pivotal role of sterol-regulatory element binding proteins (SREBPs), in the HCV-mediated stimulation of LDLR transcription. In addition, HCV negatively modulated the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that facilitates LDLR degradation. Ectopic expression of wild-type PCSK9 or gain-of-function PCSK9 mutant negatively affected HCV replication. Overall, our results demonstrate that HCV regulates LDLR expression at transcriptional and posttranslational level via SREBPs and PCSK9 to promote lipid uptake and facilitate viral proliferation. Importance: HCV modulates host lipid metabolism to promote enrichment of lipids in intracellular environment, which are essential in multiple aspects of HCV life cycle. However, very little is known about the influence of HCV on lipid uptake from the bloodstream. LDLR is involved in uptake of cholesterol rich lipid particles from bloodstream. In this study, we investigated the effect of HCV on LDLR expression and the underlying mechanism triggered by the virus to modulate LDLR expression. Our observations suggest that HCV upregulates LDLR expression at both the protein and the transcript levels and that this upregulation likely contributes toward the uptake of serum lipids by infected hepatocytes. Abrogation of HCV-mediated upregulation of LDLR inhibits serum lipid uptake and thereby perturbs HCV replication. Overall, our findings highlight the importance of serum lipid uptake by infected hepatocytes in HCV life cycle. PMID:24352472

Syed, Gulam Hussain; Tang, Huihui; Khan, Mohsin; Hassanein, Tarek; Liu, Jingwen; Siddiqui, Aleem

2014-03-01

362

N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors  

PubMed Central

N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor.

Zhang, Chun-ge; Zhu, Qiao-ling; Zhou, Yi; Liu, Yang; Chen, Wei-liang; Yuan, Zhi-Qiang; Yang, Shu-di; Zhou, Xiao-feng; Zhu, Ai-jun; Zhang, Xue-nong; Jin, Yong

2014-01-01

363

Relationship Between Apolipoprotein Concentrations and HDL Subclasses Distribution  

Microsoft Academic Search

Alterations in plasma apolipoproteins levels can influence the composition, content, and distribution of plasma lipoproteins\\u000a that affect the risk of atherosclerosis. This study assessed the relationship between plasma apolipoproteins levels, mainly\\u000a apoAI, and HDL subclass distribution. The contents of plasma HDL subclasses were determined by two-dimensional gel electrophoresis\\u000a coupled with immunodetection in 545 Chinese subjects. Compared with a low apoAI

Li Tian; Mingde Fu; Lianqun Jia; Yanhua Xu; Shiyin Long; Haoming Tian; Ying Tian

2007-01-01

364

Tissue sites of degradation of high density lipoprotein apolipoprotein A-IV in rats  

SciTech Connect

The in vivo metabolism of high density lipoprotein (HDL), labeled by incorporation of /sup 125/I-apolipoprotein (apo) A-IV, was studied in the rat and compared with the metabolism of HDL labeled with 131I-apo A-I. The /sup 125/I-apo A-IV labeled HDL was obtained by adding small amounts of radioiodinated apo A-IV to rat serum, followed by separation of the different lipoprotein fractions by chromatography on 6% agarose columns in order to avoid stripping of apolipoproteins by ultracentrifugation. Under both in vitro and in vivo conditions, the /sup 125/I-apo A-IV remained an integral component of HDL and was not exchanged to other lipoproteins, including the free apo A-IV fraction. The serum half-life, measured at between 8 and 28 hours after intravenous injection of labeled HDL, was 8.5 +/- 0.5 hours for HDL apo A-IV and 10.2 +/- 0.7 hours for HDL apo A-I. The tissue sites of catabolism of HDL apo A-IV and HDL apo A-I were analyzed in the leupeptin-model. Only the kidneys and liver showed a significant leupeptin-dependent accumulation of radioactivity. At 4 hours after injection of 125I-apo A-IV/131I-apo A-I labeled HDL, 3.5% +/- 1.0% and 8.4% +/- 2.0% of HDL apo A-IV and 4.6% +/- 1.3% and 2.6% +/- 0.6% of the HDL apo A-I were accumulated in a leupeptin-dependent process in the kidneys and liver, respectively. Immunocytochemical studies revealed that the renal localization of apo A-IV was intracellular and confined to the epithelial cells of the proximal tubuli.

Dallinga-Thie, G.M.; Van 't Hooft, F.M.; Van Tol, A.

1986-05-01

365

Hypochlorite-modified high-density lipoprotein acts as a sink for myeloperoxidase in vitro  

PubMed Central

Aims Myeloperoxidase (MPO), a cardiovascular risk factor in humans, is an in vivo catalyst for lipoprotein modification via intermediate formation of reactive chlorinating species. Among the different lipoprotein classes, anti-atherogenic high-density lipoprotein (HDL) represents a major target for modification by hypochlorous acid (HOCl), generated from H2O2 by MPO in the presence of physiological chloride concentrations. As MPO was identified as an HDL-associated protein that could facilitate selective oxidative modification of its physiological carrier, the aim of the present study was to investigate whether and to what extent modification of HDL by HOCl affects the binding affinity of MPO in vitro. Methods and results We show that binding affinity of 125I-labelled MPO to HDL markedly increases as a function of increasing extent of HOCl modification of HDL. In contrast to native HDL, HOCl–HDL potently inhibits MPO binding/uptake by endothelial cells and effectively attenuates metabolism of MPO by macrophages. Reduction of HDL-associated chloramines with methionine strongly impaired binding affinity of MPO towards HOCl–HDL. This indicates that N-chloramines generated by HOCl are regulators of the high-affinity interaction between HOCl–HDL and positively charged MPO. Most importantly, the presence of HOCl–HDL is almost without effect on the halogenating activity of MPO. Conclusion We propose that MPO-dependent modification of HDL and concomitant increase in the binding affinity for MPO could generate a vicious cycle of MPO transport to and MPO-dependent modification at sites of chronic inflammation.

Marsche, Gunther; Furtmuller, Paul G.; Obinger, Christian; Sattler, Wolfgang; Malle, Ernst

2014-01-01

366

Starvation of low-density lipoprotein-derived cholesterol induces bradyzoite conversion in Toxoplasma gondii  

PubMed Central

Background Lacking enzymes for sterol synthesis, the intracellular protozoan Toxoplasma gondii scavenges cholesterol from host cells to multiply. T. gondii has a complex life cycle consisting of two asexual stages; the proliferative stage (tachyzoite), and the latent stage characterized by tissue cysts (bradyzoite). In vitro, bradyzoite development can be induced by mimicking host immune response stressors through treatment with IFN-?, heat shock, nitric oxide, and high pH. However, the extent to which host nutrients contribute to stage conversion in T. gondii is unknown. In this study, we examined the impact of host cholesterol levels on stage conversion in this parasite. Methods Growth of T. gondii tachyzoites (ME49 strain) was investigated in Chinese hamster ovary (CHO) cells using various concentrations of low-density lipoprotein (LDL), oleic acid, or glucose. Squalestatin, which is an inhibitor of squalene synthase and is, therefore, an inhibitor of sterol synthesis, was used to treat the CHO cells. Tachyzoite to bradyzoite conversion rates were analyzed by indirect fluorescent antibody tests. Results Parasite growth was significantly enhanced by addition of exogenous LDL, whereas no such enhancement occurred with oleic acids or glucose. In ME49, growth inhibition from squalestatin treatment was not obvious. Although growth of the RH strain was unaffected by squalestatin in the presence of lipoprotein, in its absence growth of this strain was suppressed. The frequency of BAG1-positive vacuoles in ME49 increased under lipoprotein-free conditions. However, addition of exogenous LDL did not increase tachyzoite to bradyzoite conversion in this strain. Furthermore, treatment with squalestatin did not enhance stage conversion. Conclusion Our results suggest that LDL-derived cholesterol levels play a crucial role in bradyzoite conversion in T. gondii.

2014-01-01

367

Defects in the low density lipoprotein receptor gene affect lipoprotein (a) levels: multiplicative interaction of two gene loci associated with premature atherosclerosis.  

PubMed

The lipoprotein (a) [Lp(a)] contains two nonidentical protein species, apolipoprotein (apo) B-100 and a specific high molecular weight glycoprotein, apo(a). Lp(a) represents a continuous quantitative genetic trait, the genetics of which are only poorly understood. Genetic variation at the apo(a) locus affects plasma Lp(a) levels and explains at least 40% of the variability of this trait. Lp(a) levels were found to be elevated 3-fold in the plasma from patients with the heterozygous form of familial hypercholesterolemia who have one mutant low density lipoprotein receptor gene. This elevation was not due to a higher frequency of those apo(a) types that are associated with high Lp(a) levels in familial hypercholesterolemia patients. Rather Lp(a) levels were elevated for each of the apo(a) phenotypes examined. The effects of the apo(a) and low density lipoprotein receptor genes on Lp(a) levels are not additive but multiplicative. This is a situation not commonly considered in quantitative human genetics. We conclude that Lp(a) levels in plasma may be determined by variation at more than one gene locus. PMID:2524837

Utermann, G; Hoppichler, F; Dieplinger, H; Seed, M; Thompson, G; Boerwinkle, E

1989-06-01

368

Defects in the low density lipoprotein receptor gene affect lipoprotein (a) levels: multiplicative interaction of two gene loci associated with premature atherosclerosis.  

PubMed Central

The lipoprotein (a) [Lp(a)] contains two nonidentical protein species, apolipoprotein (apo) B-100 and a specific high molecular weight glycoprotein, apo(a). Lp(a) represents a continuous quantitative genetic trait, the genetics of which are only poorly understood. Genetic variation at the apo(a) locus affects plasma Lp(a) levels and explains at least 40% of the variability of this trait. Lp(a) levels were found to be elevated 3-fold in the plasma from patients with the heterozygous form of familial hypercholesterolemia who have one mutant low density lipoprotein receptor gene. This elevation was not due to a higher frequency of those apo(a) types that are associated with high Lp(a) levels in familial hypercholesterolemia patients. Rather Lp(a) levels were elevated for each of the apo(a) phenotypes examined. The effects of the apo(a) and low density lipoprotein receptor genes on Lp(a) levels are not additive but multiplicative. This is a situation not commonly considered in quantitative human genetics. We conclude that Lp(a) levels in plasma may be determined by variation at more than one gene locus. Images

Utermann, G; Hoppichler, F; Dieplinger, H; Seed, M; Thompson, G; Boerwinkle, E

1989-01-01

369

The triglyceride:high-density lipoprotein-cholesterol ratio and steno-occlusive disease in the intracranial arteries  

Microsoft Academic Search

The extent of carotid artery atherosclerosis correlates with increased plasma concentrations of total cholesterol (TC) and\\u000a low-density lipoprotein-cholesterol (LDL-C) and with a decreased plasma concentration of high-density lipoprotein-cholesterol\\u000a (HDL-C). However, emerging data suggest that a triglyceride (TG):HDL-C ratio may be a better predictor of vascular risk than\\u000a the traditional lipid measures such as TC and LDL-C. The purpose of this

Kyusik Kang; Kwangsub Lee; Sung-Hoon Chung

2011-01-01

370

Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor.  

PubMed Central

A novel and potent azetidinone inhibitor of the lipoprotein-associated phospholipase A2 (Lp-PLA2), i.e. platelet-activating factor acetylhydrolase, is described for the first time. This inhibitor, SB-222657 (Ki=40+/-3 nM, kobs/[I]=6. 6x10(5) M-1.s-1), is inactive against paraoxonase, is a poor inhibitor of lecithin:cholesterol acyltransferase and has been used to investigate the role of Lp-PLA2 in the oxidative modification of lipoproteins. Although pretreatment with SB-222657 did not affect the kinetics of low-density lipoprotein (LDL) oxidation by Cu2+ or an azo free-radical generator as determined by assay of lipid hydroperoxides (LOOHs), conjugated dienes and thiobarbituric acid-reacting substances, in both cases it inhibited the elevation in lysophosphatidylcholine content. Moreover, the significantly increased monocyte chemoattractant activity found in a non-esterified fatty acid fraction from LDL oxidized by Cu2+ was also prevented by pretreatment with SB-222657, with an IC50 value of 5.0+/-0.4 nM. The less potent diastereoisomer of SB-222657, SB-223777 (Ki=6.3+/-0.5 microM, kobs/[I]=1.6x10(4) M-1.s-1), was found to be significantly less active in both assays. Thus, in addition to generating lysophosphatidylcholine, a known biologically active lipid, these results demonstrate that Lp-PLA2 is capable of generating oxidized non-esterified fatty acid moieties that are also bioactive. These findings are consistent with our proposal that Lp-PLA2 has a predominantly pro-inflammatory role in atherogenesis. Finally, similar studies have demonstrated that a different situation exists during the oxidation of high-density lipoprotein, with enzyme(s) other than Lp-PLA2 apparently being responsible for generating lysophosphatidylcholine.

MacPhee, C H; Moores, K E; Boyd, H F; Dhanak, D; Ife, R J; Leach, C A; Leake, D S; Milliner, K J; Patterson, R A; Suckling, K E; Tew, D G; Hickey, D M

1999-01-01

371

Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein  

PubMed Central

Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ?6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

Boshtam, Maryam; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

2013-01-01

372

[Atherogenic modifications of low density lipoproteins during fibrin formation and fibrinolysis].  

PubMed

Low density lipoproteins (LDL) were modified after incubation with fibrinogen and fibronectin at physiological concentrations in presence of thrombin and, following the fibrin formation, in presence of plasmin. The modified LDL (LDL-F) isolated from plasmin digested fibrin by means of gel permeation chromatography on Sepharose 6B, were associated with fibrinogen and fibronectin degradation products. The LDL-F differed from control LDL in their physico-chemical properties: LDL-F contained the degraded apoprotein B, its electrophoretic mobility was increased, cholesterol/protein ratio as well as flotation coefficient at d = 1.063 were decreased. The effect of LDL-F on lipid accumulation was studied. Content of cholesterol esters in macrophages incubated with LDL-F was higher 3.8-fold as compared with that of the cells incubated with control LDL. Thus, after incubation of LDL with fibrinogen and thrombin, 20% of the lipoprotein was bound to fibrin. The data obtained suggest that thrombosis may promote both LDL deposition in the vascular intercellular matrix and cellular lipid accumulation. PMID:2741416

Chulkova, T M

1989-01-01

373

High relaxivity gadolinium modified high density lipoproteins as MRI contrast agents  

PubMed Central

There is an ongoing desire to produce high relaxivity, Gd-based MRI contrast agents. These may allow for lower doses to be used, which is especially important in view of the current safety concerns surrounding Gd in patients. Here we report the synthesis of a high relaxivity MRI contrast agent, by incorporating Gd-chelating lipids that coordinate two water molecules into high density lipoprotein (q=2 HDL). We compared the properties of q=2 HDL with those of an analogous HDL particle labeled with Gd-chelating lipids that coordinate only one water molecule (q=1 HDL). We found that the q=2 HDL possessed an elevated r1 of 41 mM?1s?1 compared to 9 mM?1s?1 for q=1 HDL at 20 MHz, but the q=2 HDL exhibited high R2* values at high fields, precluding imaging above 128 MHz. While carrying out this investigation we observed that enlarged, disrupted particles were formed when the synthesis was carried out above the lipid critical micelle concentration (CMC), indicating the importance of synthesis below the CMC when modifying lipoproteins in this manner. The high relaxivity of q=2 HDL means it will be an efficacious contrast agent for future MR imaging studies.

Briley-Saebo, Karen C.; Geninatti-Crich, Simonetta; Cormode, David P.; Barazza, Alessandra; Mulder, Willem J. M.; Chen, Wei; Giovenzana, Giovanni B.; Fisher, Edward A.; Aime, Silvio; Fayad, Zahi A.

2009-01-01

374

Lipid Composition Influences the Shape of Human Low-Density Lipoprotein in Vitreous Ice  

PubMed Central

Earlier cryo-electron microscopic studies have indicated that the normal low-density lipoprotein (N-LDL) has a discoid shape when its core is in the liquid-crystalline state. In the present study, we investigated whether the shape of LDL depends on the physical state and/or the lipid composition of the lipoprotein core. Using a custom-built freezing device, we vitrified N-LDL samples from either above or below the phase-transition temperature of the core (42°C and 24°C, respectively). Cryo-electron microscopy revealed no differences between these samples and indicated a discoid shape of the N-LDL particle. In contrast, triglyceride-enriched LDL (T-LDL) did not have discoid features and appeared to be quasi-spherical in preparations that were vitrified from either 42°C or 24°C. These results suggest that the shape of N-LDL is discoid, regardless of the physical state of its core, while T-LDL is more spherical. Aspects that may influence the shape of LDL are discussed.

Coronado-Gray, Andrea; van Antwerpen, Rik

2005-01-01

375

High density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis  

PubMed Central

Lipoproteins, natural nanoparticles, have a well-recognized biological role and are highly suitable as a platform for delivering imaging agents. The ease with which both the exterior and interior of the particles can be modified permits the creation of multifunctional nanoparticles for imaging as well as the delivery of therapeutics. Importantly, their endogenous nature may make them biocompatible, biodegradable and allows them to avoid the recognition of the reticuloendothelial system. In particular, high density lipoproteins (HDL) are of interest, because of their small size they can easily cross the endothelium and penetrate the underlying tissue. We summarize here the progress in establishing HDL as a vector for delivering a variety of diagnostically active materials to vulnerable atherosclerotic plaques in mouse models of atherosclerosis. By loading various types of image-enhancing compounds into either the core or surface of HDL, they can be visualized by different imaging modalities (MRI, CT, optical). By re-routing of HDL away from plaque macrophages, imaging of biological processes in diseases besides atherosclerosis may also be achieved.

Skajaa, Torjus; Cormode, David P.; Falk, Erling; Mulder, Willem J. M.

2010-01-01

376

Anti-oxidant properties of high-density lipoprotein and atherosclerosis  

PubMed Central

SUMMARY High-density lipoprotein (HDL) is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically.The best known function of HDL is the capacity to promote cellular cholesterol efflux from peripheral cells and deliver cholesterol to the liver for excretion, thereby playing a key role in reverse cholesterol transport. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease.Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Conversely, these activities are compromised in many pathological states associated with inflammation.The focus of the present review is on the anti-oxidant and anti-inflammatory functions of HDL and its individual components in relation to protection from atherosclerosis.

Podrez, Eugene A

2010-01-01

377

A high density lipoprotein from Piaractus mesopotamicus, pacu, (Osteichthyes, Characidae), is associated with paraoxonase activity.  

PubMed

We have characterized the serum lipoprotein profile and localized the serum paraoxonase activity of pacu, Piaractus mesopotamicus, a tropical fish species. The total lipoprotein profile of pacu serum obtained after KBr density ultracentrifugation shows the predominance of HDL (1.1267 g/mL). SDS-PAGE electrophoresis revealed a negligible amount of LDL. Pacu HDL was purified by gel filtration column on HPLC, and its molecular mass was estimated to be 246 kDa. Protein composition was 35%, and comprised four protein components with molecular masses of 45, 38, 25 and 12.5 kDa. Lipids represent 58% of total HDL, comprising 40% neutral lipids and 18% phospholipids by weight. The HDL contains 7% of carbohydrates, and mannose was the only sugar detected by paper chromatography in HDL hydrolysates. HDL-containing fractions showed the major paraoxonase activity. Purification of HDL resulted in a 23-fold enrichment of this activity. This is the first experimental evidence demonstrating the association of paraoxonase activity with a HDL in fish. PMID:11728631

Folly, E; Bastos, V L; Alves, M V; Bastos, J C; Atella, G C

2001-10-01

378

Calcium as a Crucial Cofactor for Low Density Lipoprotein Receptor Folding in the Endoplasmic Reticulum*  

PubMed Central

The family of low density lipoprotein (LDL) receptors mediate uptake of a plethora of ligands from the circulation and couple this to signaling, thereby performing a crucial role in physiological processes including embryonic development, cancer development, homeostasis of lipoproteins, viral infection, and neuronal plasticity. Structural integrity of individual ectodomain modules in these receptors depends on calcium, and we showed before that the LDL receptor folds its modules late after synthesis via intermediates with abundant non-native disulfide bonds and structure. Using a radioactive pulse-chase approach, we here show that for proper LDL receptor folding, calcium had to be present from the very early start of folding, which suggests at least some native, essential coordination of calcium ions at the still largely non-native folding phase. As long as the protein was in the endoplasmic reticulum (ER), its folding was reversible, which changed only upon both proper incorporation of calcium and exit from the ER. Coevolution of protein folding with the high calcium concentration in the ER may be the basis for the need for this cation throughout the folding process even though calcium is only stably integrated in native repeats at a later stage.

Pena, Florentina; Jansens, Annemieke; van Zadelhoff, Guus; Braakman, Ineke

2010-01-01

379

Effects of an American Heart Association step I diet and weight loss on lipoprotein lipid levels in obese men with silent myocardial ischemia and reduced high-density lipoprotein cholesterol  

Microsoft Academic Search

Reduced plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are a risk factor for coronary artery disease (CAD). In this study, we examined the sequential effects of an isocaloric American Heart Association (AHA) step I diet and a hypocaloric AHA step I diet (AHA step I diet + weight loss) on lipoprotein lipid levels in 14 middle-aged and older (60 ±

Leslie I. Katzel; Patricia J. Coon; Jana Dengel; Andrew P. Goldberg

1995-01-01

380

The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertriglyceridemia.  

PubMed

We evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil (1200 mg/day) versus Omacor (4 g/day), a drug containing the n-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on lipid and lipoprotein levels, low density lipoprotein (LDL) subfraction profile and LDL oxidizability. Both Omacor and gemfibrozil therapy resulted in a similar significant decrease in serum triglyceride (TG), very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol concentrations and an increase in high density lipoprotein (HDL) and LDL cholesterol concentrations. The increase in LDL cholesterol was due to a significant increase in cholesterol content of the relatively buoyant LDL subfractions LDL1, LDL2 and LDL3, whereas the relative contribution of the dense LDL subfractions LDL4 and LDL5 to total LDL tended to decrease. So, both therapies resulted in a more buoyant LDL subfraction profile, reflected by a significant increase of the value of parameter K (+10.3% on Omacor vs. +26.5% on gemfibrozil therapy, gemfibrozil vs Omacor P>0.05). Cu(2+)-induced oxidation of LDL was measured by continuous monitoring of conjugated dienes. After 12 weeks of Omacor treatment LDL appeared more prone to oxidative modification in vitro than LDL after gemfibrozil treatment, as measured by the significantly decreased lag time, preceding the onset of the lipid peroxidation. In both groups the rate of oxidation did not change with therapy. The amount of dienes formed during oxidation increased significantly on Omacor treatment, but not on gemfibrozil treatment. Plasma thiobarbituric acid reactive substances were higher after Omacor and lower after gemfibrozil treatment, although not significantly. We conclude that both Omacor and gemfibrozil have favorable effects on lipid and lipoprotein concentrations and the LDL subfraction profile. However, Omacor increased the susceptibility of LDL to oxidation, whereas gemfibrozil did not affect the resistance of LDL to oxidative modification in vitro. The clinical relevance of these changes remains to be established in the light of other postulated favorable effects of n-3 fatty acids on the course of cardiovascular disease. PMID:11058707

Stalenhoef, A F; de Graaf, J; Wittekoek, M E; Bredie, S J; Demacker, P N; Kastelein, J J

2000-11-01

381

Genetic Diagnosis of Familial Hypercholesterolemia in a South European Outbreed Population: Influence of Low Density Lipoprotein (LDL) Receptor Gene Mutations on Treatment Response to Simvastatin in Total, LDL, and High-Density Lipoprotein Cholesterol  

Microsoft Academic Search

The aims of this study were to examine the presence of mu- tations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterol- emia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis

FELIPE J. CHAVES; ANA B. GARCIA-GARCIA; MIGUEL CIVERA; MARIA E. ARMENGOD; JUAN F. ASCASO; RAFAEL CARMENA

382

Prevention of endotoxin-induced monokine release by human low- and high-density lipoproteins and by apolipoprotein A-I.  

PubMed Central

Interaction of endotoxin (lipopolysaccharide [LPS]) with human lipoproteins is known to prevent the LPS-induced activation of human monocytes and release of cytokines (monokines). LPS was exposed to lipoprotein classes separated by ultracentrifugation and to apolipoprotein A-I. Then monocytes were added, and the LPS activation of monocytes was determined by measuring the induced monokines. Failure of LPS to induce monokine release was called LPS inactivation caused by lipoproteins or apolipoproteins. The LPS inactivation is shown to be a function of low-density lipoproteins. High-density lipoproteins inactivate LPS to a much lesser extent. The very-low-density lipoproteins cannot inactivate LPS. Lipid components seemed not absolutely required for LPS inactivation, because purified human apolipoprotein A-I without its physiological lipid complement also inhibits LPS-induced monokine release.

Flegel, W A; Baumstark, M W; Weinstock, C; Berg, A; Northoff, H

1993-01-01

383

Long-term ethanol consumption impairs reverse cholesterol transport function of high-density lipoproteins by depleting high-density lipoprotein sphingomyelin both in rats and in humans  

PubMed Central

Moderate alcohol consumption has been linked to lower incidence of coronary artery disease due to increased plasma high-density lipoprotein (HDL), whereas heavy drinking has the opposite effect. Because of the crucial role of HDL in reverse cholesterol transport and positive correlation of HDL sphingomyelin (SM) content with cholesterol efflux, we have compared HDL SM content with its reverse cholesterol transport capacity both in rats fed ethanol on long-term basis and alcoholic individuals. In rats, SM HDL content was decreased in the ethanol group (?15.4%, P < .01) with a concomitant efflux decrease (?21.0%, P < .01) compared to that in controls. Similarly, HDL from the ethanol group, when compared with HDL from the control group, exhibited 13.8% (P < .05) less cholesterol uptake with control-group hepatocytes and 35.0% (P < .05) less cholesterol uptake with ethanol-group hepatocytes. Conversely, hepatocytes from the ethanol group, when compared with hepatocytes from the control group, exhibited 31.0% (P < .01) less cholesterol uptake with control-group HDL and 48.0% (P < .01) less with ethanol-group HDL. In humans, SM content in plasma HDL was also decreased in chronically alcoholic individuals without liver disease (?51.5%, P < .01) and in chronically alcoholic individuals with liver disease (?51.3%, P < .01), compared with nondrinkers. Concomitantly, in alcoholic individuals without liver disease, both efflux and uptake were decreased by 83.0% and 54.0% (P < .01), respectively, and in chronically alcoholic individuals with liver disease by 84.0% and 61.0% (P < .01), respectively, compared with nondrinkers. Based on these findings, we conclude that long-term ethanol consumption significantly impairs not only cholesterol efflux function of HDL by decreasing its SM content but also cholesterol uptake by affecting presumably hepatocyte receptors for HDL.

Marmillot, Philippe; Munoz, Jennifer; Patel, Sanket; Garige, Mamatha; Rosse, Richard B.; Lakshman, M. Raj

2007-01-01

384

Tetranitromethane modification of human high density lipoprotein (HDL3): inactivation of high density lipoprotein binding is not related to cross-linking of phospholipids to apoproteins.  

PubMed

Treatment of human high density lipoprotein (HDL) with tetranitromethane (TNM) inhibits its binding to HDL-specific binding sites of cells and isolated membranes. The mechanism of this inhibition, however, is not known; during treatment of HDL with TNM, in addition to the expected nitration of tyrosine residues, cross-linking of lipids to apoproteins and of apoproteins to one another occurs. In order to determine whether the cross-linking of lipids to apoproteins occurs through the carbon-carbon double bonds in the acyl chains, and to determine whether the cross-linking of phospholipids to apoproteins is a possible mechanism of inhibition of binding, we have prepared a reconstituted HDL3 in which the native phospholipids were replaced with dimyristoyl phosphatidylcholine (DMPC). As a control, a reconstituted HDL3 (C-r-HDL3) was also prepared using the total apoproteins and the total lipid constituents of native HDL3. The reconstituted DMPC-containing HDL3 (DMPC-r-HDL3) was similar to native HDL3 and to C-r-HDL3 in its agarose gel electrophoretic mobility, in its chemical composition, and in its binding to rat liver plasma membranes. When treated with TNM, DMPC-r-HDL3, like the native HDL3 and C-r-HDL3, lost its ability to bind to the HDL binding sites of rat liver plasma membranes, as determined by competitive binding assays with 125I-labeled human HDL3 as the tracer. Nitrated DMPC-r-HDL3 contained only traces of phospholipids covalently linked to apoproteins, whereas 21-26% of the total phospholipids were cross-linked to apoproteins of nitrated C-r-HDL3 and nitrated native HDL3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3572257

Chacko, G K; Lund-Katz, S; Johnson, W J; Karlin, J B

1987-03-01

385

Use of total cholesterol/albumin ratio as an alternative to high density lipoprotein cholesterol measurement.  

PubMed Central

In a study of apparently healthy males, we noted a correlation between serum albumin and high density lipoprotein cholesterol (HDL-C) (r = 0.32, p less than 0.001). We then correlated the total cholesterol:albumin ratio (TC:Alb) with the TC:HDL-C ratio (r = 0.89, p less than 0.001). We used the TC:Alb ratio to determine whether this was better than TC by itself in predicting whether an individual had a TC:HDL-C ratio of less than or greater than or equal to 5. The ratio performed better than TC and correctly classified 89% of individuals (66% with TC) (p less than 0.001). Since measurements of TC and Alb are routinely available on multichannel analysers, use of this ratio would provide a less expensive alternative to HDL-C measurement.

Nanji, A A; Reddy, S

1983-01-01

386

Flavonoids from Lindera glauca Blume as low-density lipoprotein oxidation inhibitors.  

PubMed

In order to identify antioxidant flavonoids from Lindera glauca Blume, we performed phytochemical analysis of L. glauca Blume heartwood and isolated eight flavonoids - lindeglaucol (1), lindeglaucone (2), cilicicone B (3), tamarixetin 3-O-?-L-rhamnoside (4), procyanidin A2 (5), cinnamtannin B1 (6), cinnamtannin D1 (7), and procyanidin A1 (8) - through repeated column chromatography over silica gel (SiO?), octadecyl silica gel (ODS) and Sephadex LH-20. The chemical structures of compounds 1-8 were elucidated from spectroscopic data (NMR, IR and MS). The low-density lipoprotein oxidation inhibitory activities of the isolated compounds were evaluated in vitro by using the thiobarbituric acid reactive substances assay. Compounds 5-8 exhibited high inhibition activity, comparable to the positive control butyl hydroxyl toluene. Compounds 2 and 3 were slightly less active, while 1 and 4 expressed low activity. PMID:24499267

Huh, Gyu-Won; Park, Ji-Hae; Kang, Ji-Hyun; Jeong, Tae-Sook; Kang, Hee Cheol; Baek, Nam-In

2014-01-01

387

High-Density Lipoprotein Proteomics: Identifying New Drug Targets and Biomarkers by Understanding Functionality  

PubMed Central

Recent proteomics studies on human plasma high-density lipoprotein (HDL) have discovered up to 50 individual protein constituents. Many of these have known functions that vary surprisingly from the lipid transport roles commonly thought to mediate HDL’s ability to protect from coronary artery disease. Given newly discovered roles in inflammation, protease inhibition, complement regulation, and innate immunity, many have begun to view HDL as a broad collection of distinct particle subfamilies, each distinguished by unique protein compositions and functions. Herein we review recent applications of high-resolution proteomics to HDL and summarize evidence supporting the idea of HDL functional subspeciation. These studies have set the stage for a more complete understanding of the molecular basis of HDL functional heterogeneity and hold promise for the identification of new biomarkers that can predict disease or evaluate the success of clinical interventions.

Gordon, Scott; Durairaj, Anita; Lu, Jason L.; Davidson, W. Sean

2010-01-01

388

Spanish sparkling wines (Cavas) as inhibitors of in vitro human low-density lipoprotein oxidation.  

PubMed

Forty-seven dealcoholized sparkling wines (cava) from the Penedès area in Spain were tested for their antioxidant activity in a low-density lipoprotein system. The effect of different quality-related parameters, such as harvest year or grape variety, was investigated. Twenty-two phenolic compounds were separated by high-performance liquid chromatography and identified by comparing their retention time and their ultraviolet spectra with those of pure standards. When tested at the same total phenol concentration, the antioxidant activity of these white sparkling wines was found to be similar to that reported for red wines. This activity was positively correlated with the total phenolic content, trans-caffeic acid, coumaric acid, protocatechuic acid, and quercetin 3-glucuronide. The wines made of the classic cava wine coupage had superior antioxidant activity compared to those of other cultivars. PMID:10794609

Satué-Gracia, M T; Andrés-Lacueva, C; Lamuela-Raventós, R M; Frankel, E N

1999-06-01

389

Inhibition of human low-density lipoprotein oxidation in vitro by ginger extracts.  

PubMed

Abstract Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in atherosclerotic plaque formation. Currently, there is a renewed interest in ginger because of its antioxidants and cardioprotective properties. The effects of ethanol, methanol, ethyl acetate, and hexane solvent extracts of ginger and pure major ginger constituents on Cu(2+)-induced oxidation of human LDL in vitro were examined. The LDL oxidation inhibition by ethanol, methanol, ethyl acetate, and hexane extracts of ginger was 71%, 76%, 67%, and 67%, respectively, at their optimum extraction conditions. Inhibition of LDL oxidation by water extracts of ginger, which was prepared by ultrasonic-assisted extraction conditions of 52°C for 15?min, was about 43%. Phenolic bioactives of ginger-6-gingerols, 8-gingerols, 10-gingerols, and 6-shogaol-seem to be strong inhibitors of Cu(+2)-induced LDL oxidation. Overall, ginger extracts, including the water extract possess the antioxidant activities to inhibit human LDL oxidation in vitro. PMID:24404979

Gunathilake, K D Prasanna P; Rupasinghe, H P Vasantha

2014-04-01

390

Pharmacogenetics of paraoxonase activity: elucidating the role of high-density lipoprotein in disease  

PubMed Central

PON1 is a key component of high-density lipoproteins (HDLs) and is at least partially responsible for HDL's antioxidant/atheroprotective properties. PON1 is also associated with numerous human diseases, including cardiovascular disease, Parkinson's disease and cancer. In addition, PON1 metabolizes a broad variety of substrates, including toxic organophosphorous compounds, statin adducts, glucocorticoids, the likely atherogenic l-homocysteine thiolactone and the quorum-sensing factor of Pseudomonas aeruginosa. Numerous cardiovascular and antidiabetic pharmacologic agents, dietary macronutrients, lifestyle factors and antioxidant supplements affect PON1 expression and enzyme activity levels. Owing to the importance of PON1 to HDL function and its individual association with diverse human diseases, pharmacogenomic interactions between PON1 and the various factors that alter its expression and activity may represent an important therapeutic target for future investigation.

Kim, Daniel Seung; Marsillach, Judit; Furlong, Clement E; Jarvik, Gail P

2014-01-01

391

High-density lipoproteins in the prevention of cardiovascular disease: changing the paradigm.  

PubMed

High-density-lipoprotein cholesterol (HDL-C) has been identified in population studies as an independent inverse predictor of cardiovascular events. Although the causal nature of this association has been questioned, HDL and its major protein, apolipoprotein (apo)A1, have been shown to prevent and reverse atherosclerosis in animal models. In addition, HDL and apoA1 have several putatively atheroprotective functions, such as the ability to promote efflux of cholesterol from macrophages in the artery wall, inhibit vascular inflammation, and enhance endothelial function. Therefore, HDL-C and apoA1 have been investigated as therapeutic targets for coronary heart disease. However, recent clinical trials with drugs that raise HDL-C, such as niacin and inhibitors of cholesteryl ester transfer protein, have been disappointing. Here, we review the current state of the science regarding HDL as a therapeutic target. PMID:24713591

Tuteja, S; Rader, D J

2014-07-01

392

Newer therapeutic strategies to alter high-density lipoprotein level and function.  

PubMed

Measurements of low levels of high-density lipoprotein (HDL) cholesterol have been identified as a risk factor for premature coronary artery disease, however, to date, current pharmacologic approaches for raising HDL have provided little benefit, if at all, in reducing cardiovascular outcomes. It has been shown that HDL can modify many aspects of plaque pathogenesis. Its most established role is in reverse cholesterol transportation, but HDL can also affect oxidation, inflammation, cellular adhesion, and vasodilatation. Considering these potential benefits of HDL, newer treatments have been developed to modify HDL activity, which include the use of oral cholesteryl ester transfer protein inhibitors, apolipoprotein (apo)A-I infusions, apoA-I mimetics, drugs to increase apoA-I synthesis, and agonists of the liver X receptor. These new therapies are reviewed in this article. PMID:23707991

Bosch, Nicholas; Frishman, William H

2014-01-01

393

Tailoring of Biomimetic High-Density Lipoprotein (HDL) Nanostructures Changes Cholesterol Binding and Efflux  

PubMed Central

Gold nanoparticles (Au NPs) were employed as templates to synthesize spherical, high-density lipoprotein (HDL) biomimics (HDL Au NPs) of different sizes and surface chemistries. The effect of size and surface chemistry on the cholesterol binding properties and the ability of the HDL Au NPs to efflux cholesterol from macrophage cells were measured. Results demonstrate that Au NPs may be utilized as templates to generate nanostructures with different physical characteristics that mimic natural HDL. Furthermore, the properties of the HDL Au NPs may be tailored to modulate the ability to bind cholesterol in solution and efflux cholesterol from macrophages. From the conjugates tested, the optimum size and surface chemistry for preparing functional Au NP-templated HDL biomimics were identified.

Luthi, Andrea J.; Zhang, Heng; Kim, Dongwoo; Giljohann, David A.; Mirkin, Chad A.; Thaxton, C. Shad

2014-01-01

394

Patients with low levels of high-density lipoprotein cholesterol: to treat or not to treat?  

PubMed

Clinical evidence indicates that a low level of high-density lipoprotein cholesterol (HDL-C) is a major risk of atherosclerosis. Raising HDL-C reduces this risk significantly, making HDL-C levels an important target of treatment for dyslipidaemia, especially in pre-existent atherosclerosis. HDL-C is protective against atherosclerosis, largely due to its function of reverse cholesterol transport. Additionally, some important roles include fibrinolysis, antioxidant functions, and reduction of platelet aggregability. A number of agents potentially modify HDL favourably. Niacin is the most potent HDL-C raising agent currently available in clinical practice, followed by fibrates. CETP inhibitors show greater HDL-C rising, but are still used in trial settings only. HDL mimetic agents are another group of agents that offer much promise. Clinical outcome data are awaited for these newer therapeutic agents. PMID:16172771

Tavintharan, S; Lim, S C; Sum, C F

2005-10-01

395

High density lipoprotein cholesterol: an evolving target of therapy in the management of cardiovascular disease  

PubMed Central

Since the pioneering work of John Gofman in the 1950s, our understanding of high density lipoprotein cholesterol (HDL-C) and its relationship to coronary heart disease (CHD) has grown substantially. Numerous clinical trials since the Framingham Study in 1977 have demonstrated an inverse relationship between HDL-C and one’s risk of developing CHD. Over the past two decades, preclinical research has gained further insight into the nature of HDL-C metabolism, specifically regarding the ability of HDL-C to promote reverse cholesterol transport (RCT). Recent attempts to harness HDL’s ability to enhance RCT have revealed the complexity of HDL-C metabolism. This review provides a detailed update on HDL-C as an evolving therapeutic target in the management of cardiovascular disease.

Kapur, Navin K; Ashen, Dominique; Blumenthal, Roger S

2008-01-01

396

Decrease in high density lipoprotein cholesterol during prolonged storage. CELL Study Group.  

PubMed

Different studies on the stability of high density lipoprotein cholesterol (HDL) in frozen serum or plasma have yielded conflicting results, namely increase, decrease, or no change at all during prolonged storage under freezing conditions. As part of a major trial on lipid-lowering strategies we statistically demonstrated a time-related decrease in HDL cholesterol during storage up to 46 months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been analysed fresh and then stored from 26 to 46 months, using the dextran sulphate 500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on time was performed. The slope was significantly negative (p < 0.0005). The regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e. after 6 months' storage at -20 degrees C there was almost a 1% decrease in the HDL cholesterol concentration per month of storage. PMID:8743100

Ekbom, T; Lindholm, L H; Lanke, J; Nilsson-Ehle, P

1996-04-01

397

Beneficial effect of gemfibrozil on the chemical composition and oxidative susceptibility of low density lipoprotein: a randomized, double-blind, placebo-controlled study  

Microsoft Academic Search

Previous reports have shown that administration of fibrates can reduce coronary events and also improve plasma lipid levels. Oxidative modification of low density lipoprotein has been implicated in the pathogenesis of atherosclerosis, and the resistance of low density lipoprotein (LDL) to in vitro oxidation has been found to be correlated with the extent of atherosclerosis. We performed a double-blind, placebo-controlled

Hiroshi Yoshida; Toshitsugu Ishikawa; Makoto Ayaori; Hideki Shige; Toshimitsu Ito; Michio Suzukawa; Haruo Nakamura

1998-01-01

398

Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion  

PubMed Central

Abstract Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein (LDL) in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation (ERAD) by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regulated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autophagy and postprandial activation of the unfolded protein response (UPR) may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.

Fisher, Eric; Lake, Elizabeth; McLeod, Roger S

2014-01-01

399

Characterization of a 95 kDa high affinity human high density lipoprotein-binding protein.  

PubMed

A new human 95 kDa high density lipoprotein (HDL)-binding protein (HBP) corresponding to a high affinity HDL-binding site with K(d) = 1.67 microg/mL and a capacity of 13.4 ng/mg was identified in human fetal hepatocytes. The HDL binding with the 95 kDa HBP plateaus at 2.5-5 microg/mL under reducing and nonreducing conditions. The association of HDL(3) with the 95 kDa HBP plateaued in 15-30 min while dissociation was complete in 30 min. HDL(3), apoA-I, and apoA-II were recognized by the 95 kDa HBP while low density lipoproteins (LDL) and tetranitromethane-modified HDL were not. The 95 kDa HBP predominantly resides on the surface of cells since trypsin treatment of HepG2 cells eliminated nearly 70% of HDL binding. All studied human cells and cell lines (HepG2, Caco-2, HeLa, fibroblasts, SKOV-3, PA-I) demonstrated the presence of the 95 kDa protein. Both RT-PCR and Western blotting for HB-2/ALCAM were negative in human fetal hepatocytes while Gp96/GRP94 was clearly differentiated from the 95 kDa HBP by two-dimensional electrophoretic mobility. Moreover, deglycosylation of HepG2 membrane preparations did not affect either HDL binding to the 95 kDa HBP or its size, while in contrast it affected the molecular weights of HB-2/ALCAM and SR-BI/CLA-1. We conclude that the 95 kDa HBP is a new HDL receptor candidate widely expressed in human cells and cell lines. PMID:11284697

Bocharov, A V; Vishnyakova, T G; Baranova, I N; Patterson, A P; Eggerman, T L

2001-04-10

400

Metabolic fate of sphingomyelin of high-density lipoprotein in rat plasma  

SciTech Connect

The metabolic fate of high density lipoprotein (HDL) sphingomyelin in plasma was studied in rats over a 24-hr period after injection of HDL containing sphingomyelin which was {sup 14}C-labeled in the stearic (18:0) or lignoceric acid (24:0) moiety and {sup 3}H-labeled in the choline methyl groups. Decay of label in plasma followed three phases. The first two phases were similar for both isotopes and both types of sphingomyelin (t1/2 approximately 10 and 110 min). However, during the third phase (from 10 hr after injection), {sup 3}H label disappeared more slowly than {sup 14}C label from 18:0 sphingomyelin, whereas the {sup 3}H/{sup 14}C ratio remained relatively constant when 24:0 sphingomyelin was used. Intact, doubly-labeled 18:0 sphingomyelin disappeared from HDL rapidly (t1/2 = 38 min) by tissue uptake and by transfer to very low density lipoprotein (VLDL). VLDL contained up to 12% of the sphingomyelin 1 hr after injection. This is the first demonstration of a transfer in vivo of sphingomyelin from HDL to VLDL. A similarly rapid transfer was also observed in vitro. Some nontritiated, ({sup 14}C)18:0 or ({sup 14}C)24:0 sphingomyelin was redistributed more slowly into HDL. Doubly-labeled phosphatidylcholine appeared in VLDL and HDL within 1 hr after injection and reached 1.8 and 2.1% of the injected {sup 14}C and {sup 3}H in VLDL at 1 hr, and 4.8 and 6.9% in HDL at 3 hr, respectively.

Bentejac, M.; Bugaut, M.; Delachambre, M.C.; Lecerf, J. (Universite de Dijon-BP 138 (France))

1990-10-01

401

Low density lipoprotein receptor-related protein polymorphisms are not risk factors for venous thromboembolism.  

PubMed

Low-density lipoprotein receptor-related protein is a receptor involved in factor VIII catabolism. In spite of elevated factor VIII coagulant activity levels being a well-established independent risk factor for venous thrombosis, the origin of this abnormality is unknown. In this study, we investigated the role of polymorphisms C220T (exon 22), A775P (exon 14) and D2080N (exon 39) in the gene coding for this receptor in 249 patients (100 males/149 female, mean age 36.5 SD:11 years) with venous thromboembolism and 366 controls (155 male/211 females, mean age 38 SD:11 years ) matched by age and gender. The polymorphisms C220T (CT OR: 0.9, 95%CI: 0.6-1.2; TT OR: 1.0, 95%CI: 0.6-1.5) and D2080N (OR: 0.8, 95%CI: 0.3-2.4) were not associated to thrombosis susceptibility while the polymorphism A775P was identified in neither patients or controls. D2080N polymorphism was associated with factor VIII and von Willebrand factor levels, in the control group. Heterozygous individuals (DN), compared with homozygotes individuals (DD), presented lower levels of factor VIII (mean difference: 42.3 IU/dL, 95%CI: 5.7-78.9) and von Willebrand factor (mean difference: 34.8 IU/dL, 95%CI: 4.9-64.6). In conclusion, we demonstrated an association between D2080N polymorphism with factor VIII and von Willebrand factor levels in Brazilian normal individuals. However, none of the three polymorphisms in low-density lipoprotein receptor related protein gene were related to venous thrombosis risk in these patients. PMID:17889283

Mello, Tayana B T; Siqueira, Lúcia H; Montavão, Silmara A L; Ozello, Margarete C; Annichino-Bizzacchi, Joyce M

2008-01-01

402

Low high-density lipoprotein cholesterol: current status and future strategies for management  

PubMed Central

Atherosclerotic cardiovascular disease is the foremost cause of death and disability in the Western world, and it is rapidly becoming so in the developing nations. Even though the use of statin therapy aiming at the low-density lipoprotein cholesterol (LDL) has significantly reduced cardiovascular events and mortality, substantial residual cardiac events still occur in those being treated to the currently recommended targets. In fact, residual risk is also seen in those who are treated “aggressively” such as the “high risk” patients so defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). Consequently, one must look for the predictors of risk beyond LDL reduction. High-density lipoprotein cholesterol (HDL) is the next frontier. The protectiveness of elevated HDL against atherosclerosis is well described in the literature. HDL subdues several atherogenic processes, such as oxidation, inflammation, cell proliferation and thrombosis. It also helps mobilize the excess LDL via reverse cholesterol transport. Low levels of HDL have been shown to be independent predictors of risk. Thus, therapies to raise the HDL hold promise for additional cardiac risk reduction. In this regard, several randomized trials have recently tested this hypothesis, especially in patients at high risk. In addition to the use of aggressive lifestyle modification, clinical outcomes have been measured following augmentation of HDL levels with various treatment modalities, including aggressive statin therapy, combination therapy with fibrates and niacin, and direct HDL-raising drug treatments. These data for low HDL as an independent risk factor and as the new treatment target are reviewed in this paper.

Singh, Vibhuti; Sharma, Rakesh; Kumar, Ajoy; Deedwania, Prakash

2010-01-01

403

Improved glucose control decreases the interaction of plasma low-density lipoproteins with arterial proteoglycans.  

PubMed

The entrapment and retention of plasma low-density lipoproteins (LDL) by arterial proteoglycans (PG) is a process central to atherogenesis. We postulated therefore that accelerated atherosclerosis of diabetic individuals may result from hyperglycemia-associated modifications in LDL that enhance their interaction with arterial PG. To evaluate the role of clinical treatment on this process, LDL-PG binding was evaluated in uncontrolled type 2 diabetic subjects on monotherapy followed by combination therapy. After a 4-week washout (baseline), subjects were randomized to receive glipizide GITS monotherapy (20 mg/d, n = 12) or metformin monotherapy (2.5 g/d, n = 8) for 6 weeks followed by combination treatment with both agents for 12 weeks. Fasting blood glucose and fructosamine were significantly reduced with monotherapy and further reduced with combination therapy P <.01). With combination therapy, glycated hemoglobin (GHb) levels were significantly reduced from baseline for the group initially treated with glipizide GITS (8.5% v 10.5%, P <.0005), or initially with metformin (6.7% v 9.7%, P <.0005). No significant changes in total plasma cholesterol (TPC), LDL, high-density lipoprotein (HDL), or triglycerides (TG) were measured after monotherapy or combination therapy. Plasma LDL was isolated by differential ultracentrifugation. In an in vitro binding assay, LDL from subjects on combination glipizide GITS/metformin demonstrated significantly less binding to arterial PG than LDL obtained after monotherapy with either agent (7.6 +/- 0.5 v 10.7 +/- 0.9 microg LDL cholesterol/microg PG [mean +/- SEM], P <.05). These data demonstrate that combination treatment with glipizide GITS/metformin will further improve glucose control in type 2 diabetic subjects and may favorably improve diabetes-associated modification of LDL-arterial PG binding. PMID:12370838

Edwards, Iris J; Terry, James G; Bell-Farrow, Audrey D; Cefalu, William T

2002-10-01

404

Comparison of two methods of estimation of low density lipoprotein cholesterol, the direct versus friedewald estimation.  

PubMed

Current recommendations of the Adult Treatment Panel and Adolescents Treatment Panel of National Cholesterol Education Program make the low-density lipoprotein cholesterol (LDL-C) levels in serum the basis of classification and management of hypercholesterolemia. A number of direct homogenous assays based on surfactant/solubility principles have evolved in the recent past. This has made LDL-C estimation less cumbersome than the earlier used methods. Here we compared one of the direct homogenous assays with the widely used Friedewald's method of estimation of LDL-C to see the differences and correlation. We used direct homogenous assay kit to estimate serum LDL-C and high-density lipoprotein cholesterol (HDL-C). Serum Triglyceride (TG) and Total Cholesterol (TC) was estimated and using Friedewald's formula LDL-C was calculated. The LDL-C level obtained by both methods in 893 fasting serum samples were compared. The statistical methods used were paired t-test and Pearson's correlation.There was significant difference in the mean LDL-C levels obtained by the two methods at the TG levels <200 mg/dl (p<0.02) and TC levels >150 mg% (p<0.001). The correlation coefficient (r) between Friedewald's and direct assay estimation was 0.88. Friedewald's method classified 23.5 % of patients as high cardiac risk whereas there were 17.58% by direct assay.Both had good correlation even though the serum triglyceride and total cholesterol levels affect the difference in LDL-C estimated by both methods. Taking into account the cost and performance, Friedewald's method is as good or even better for classifying and managing patients. PMID:23105534

Sahu, Suchanda; Chawla, Rajinder; Uppal, Bharti

2005-07-01

405

Chitin-glucan fiber effects on oxidized low-density lipoprotein: a randomized controlled trial  

PubMed Central

Background/objectives: Elevated oxidized low-density lipoprotein (OxLDL) may promote inflammation, and is associated with increased risk of atherosclerotic coronary heart disease and worsening complications of diabetes mellitus. The primary objective of this study was to evaluate the efficacy of chitin-glucan (CG), alone and in combination with a potentially anti-inflammatory olive oil (OO) extract, for reducing OxLDL in subjects with borderline to high LDL cholesterol (LDL-C) levels. Subjects/methods: This 6-week, randomized, double-blind, placebo-controlled study of a novel, insoluble fiber derived from the Aspergillus niger mycelium, CG, evaluated 130 subjects free of diabetes mellitus with fasting LDL-C 3.37–4.92?mmol/l and glucose ?6.94?mmol/l. Participants were randomly assigned to receive CG (4.5?g/day; n=33), CG (1.5?g/day; n=32), CG (1.5?g/day) plus OO extract (135?mg/day; n=30), or matching placebo (n=35). Results: Administration of 4.5?g/day CG for 6 weeks significantly reduced OxLDL compared with placebo (P=0.035). At the end of study, CG was associated with lower LDL-C levels relative to placebo, although this difference was statistically significant only for the CG 1.5?g/day group (P=0.019). CG did not significantly affect high-density lipoprotein cholesterol, triglycerides, glucose, insulin or F2-isoprostane levels. Adverse events did not substantively differ between treatments and placebo. Conclusions: In this 6-week study, CG (4.5?g/day) reduced OxLDL, an effect that might affect the risk for atherosclerosis.

Bays, H E; Evans, J L; Maki, K C; Evans, M; Maquet, V; Cooper, R; Anderson, J W

2013-01-01

406

Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins.  

PubMed

The aim of our study was to analyze the relationships between atherosclerosis and endothelin-converting enzyme-1 (ECE-1). Four-week-old C57BL/6J [wild-type (WT)] and apolipoprotein E-deficient (apoE) mice were fed with a standard or Western-type fat diet for 8 wks. ApoE showed atherosclerotic lesions in the aorta, higher blood pressure and vascular lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) protein content than WT. ApoE showed a significant increase in ECE-1 protein content and mRNA expression in aorta, lung, and kidney, without changes in heart. When an ECE-1 inhibitor, FR-901533, was administered to them, blood pressure decreased in apoE on fat diet versus apoE on normal diet