LIPOPROTEINS FOR RESEARCH

Non–High-Density Lipoprotein Cholesterol Concentration is Associated with the Metabolic Syndrome among US Youth Aged 12-19 Years

noreply@blogger.com (Diagnostic Research) — Mon, 09 May 2011 20:53:00 +0000

Objective
To test the hypothesis that the concentration of non–high-density lipoprotein cholesterol (non–HDL-C) is associated with the metabolic syndrome (MetS) in youth.

Study design
Data on children and adolescents aged 12-19 years (n = 2734) from the cross-sectional National Health and Nutrition Examination Survey 1999-2004 were analyzed.

Results
Depending on the definition of MetS used, the mean non–HDL-C concentration among youth with MetS ranged from 144.2 to 155.8 mg/dL, compared with 108.8-109.1 mg/dL in those without MetS (all P < .001). The MetS prevalence ranged from 6.9% to 11.7% in youth with a non–HDL-C concentration of 120–144 mg/dL and from 21.5% to 23.4% in those with a concentration ≥145 mg/dL—both significantly higher than the prevalence of 1.9%-3.4% in youth with a concentration <120 mg/dL (all P < .001). After adjustment for potential confounders, youth with a non–HDL-C concentration ≥120 mg/dL or ≥145 mg/dL were about 3 or 4 times more likely to have MetS compared with those with a non–HDL-C <120 mg/dL or <145 mg/dL (all P < .001).

Conclusions
Fasting non–HDL-C concentration was strongly associated with MetS in US youth. Our results support the use of non–HDL-C thresholds of 120 mg/dL and 145 mg/dL to indicate borderline and high MetS risk, respectively.

Abbreviations: apo, Apolipoprotein; AUC, Area under the curve; BMI, Body mass index; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; DBP, Diastolic blood pressure; IDF, International Diabetes Federation; IDL-C, Intermediate-density lipoprotein cholesterol; LDL-C, Low-density lipoprotein cholesterol; MetS, Metabolic syndrome; NCEP/ATP III, Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III); NHANES, National Health and Nutrition Examination Survey; Non–HDL-C, Non–high-density lipoprotein cholesterol; PDAY, Pathobiological Determinants of Atherosclerosis in Youth; ROC, Receiver operating curve; SBP, Systolic blood pressure; VLDL-C, Very–low-density lipoprotein cholesterol

The Journal of Pediatrics
Volume 158, Issue 2, February 2011, Pages 201-207

Food debate boils again: good egg or bad egg?

noreply@blogger.com (Diagnostic Research) — Mon, 15 Nov 2010 19:58:00 +0000

In the 1980s, eggs were the dietary equivalent of slow-acting poison.

Over the next 20 years, a mountain of research showing that eggs do not have a major impact on cholesterol levels, combined with pricey marketing campaigns from egg producers, helped to clear their name. Now, eggs occupy coveted positions on brunch menus across the country and are even growing popularity as producers fortify them with omega-3 fatty acids and offer organic, cage-free and free-run varieties.

Then, a few days ago, Canadian researchers made waves when they said one egg yolk is worse, cholesterol-wise, than KFC’s Double Down sandwich, a notorious fast-food legend that replaces the traditional bun with two pieces of chicken slathered with bacon, sauce and cheese. The researchers published a report in the Canadian Journal of Cardiology warning that egg consumption can be dangerous to a person’s health and that it is wrong to assume that dietary cholesterol from eggs is harmless.

“Dietary cholesterol, including egg yolks, is harmful to the arteries,” the report says. “Stopping the consumption of egg yolks after a stroke or [heart attack] would be like quitting smoking after a diagnosis of lung cancer: a necessary action, but late.”

“Dietary cholesterol, including egg yolks, is harmful to the arteries,” the report says. “Stopping the consumption of egg yolks after a stroke or [heart attack] would be like quitting smoking after a diagnosis of lung cancer: a necessary action, but late.”

The more things change, it seems, the more they stay the same.

But does this new report mean that egg-yolk naysayers were right all along?

Cholesterol emerged as a nutritional bogeyman in the 1960s, pushing some Canadians to reject butter in favour of margarine and to abandon eggs altogether. Sweeping public-health campaigns were launched to warn citizens of the perils of egg consumption amid fears that cholesterol in the yolks was a major contributor to cardiovascular problems.

The thinking was that the dietary cholesterol found in eggs could significantly boost levels of blood cholesterol found naturally in the body and consequently raise an individual’s risk of developing heart disease.

Over time, however, a growing amount of research began to suggest that dietary cholesterol – or the cholesterol found in food we eat – has less of an impact than originally believed on the body’s overall levels.

Most of the cholesterol circulating in the bloodstream is actually produced in the liver, research has shown. The rest is derived from dietary sources, such as the cholesterol found in egg yolks, dairy products, meats and other foods.

Although cholesterol has long suffered from a negative public image, it plays an essential role in the proper function of cell membranes and helps the body produce important vitamins and bile and perform other processes.

Although cholesterol has long suffered from a negative public image, it plays an essential role in the proper function of cell membranes and helps the body produce important vitamins and bile and perform other processes.

There are two types of cholesterol: low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL carries cholesterol to the body’s cells from the liver and is known as “bad” cholesterol because when there is too much of it, it promotes the build-up of plaque in arteries, which is a risk factor for cardiovascular disease. HDL cholesterol, on the other hand, is considered “good” because it helps to carry LDL cholesterol away from artery walls.

A study published in the Journal of the American Medical Association in April, 1999, found that people who consumed an egg a day did not face an increased risk of heart attack or stroke. It was a definitive piece of evidence that helped to repair the reputation of eggs as part of a healthy diet, when consumed in moderation.

David Spence, a stroke-prevention expert at the University of Western Ontario and co-author of the new report questioning the value of eggs, said the study, and others like it, are flawed. He pointed out that diabetics in the 1999 study faced higher cardiovascular risks with increased egg consumption. Similar problems may not have been detected in healthy patients because the study did not follow them long enough, he added.

Dr. Spence said marketing campaigns have wrongly convinced Canadians that they can safely consume eggs without a fear of long-term health risks.

But his opinions clash with a wider consensus in the medical community.

In the years since the 1999 study was published, more research has shown that saturated and trans fats are much more likely to raise an individual’s blood cholesterol levels and fuel the risk of heart problems.

Of course, there are some caveats. Certain people are more sensitive to the effects of dietary cholesterol than others and need to watch their consumption to avoid potential problems. People who are at an increased risk of heart attack, stroke or other cardiovascular problems should also watch their intake of dietary cholesterol, said Rosie Schwartz, a Toronto-based dietitian and author.

But she emphasized that Canadians should not fixate on cholesterol alone. High blood pressure, a diet high in fat, being overweight and a sedentary lifestyle are all factors that can contribute to serious health problems.

“We need to really look at all the issues of heart disease,” Ms. Schwartz said.

High-density lipoproteins and cardiovascular disease: 2010 update.

noreply@blogger.com (Diagnostic Research) — Wed, 15 Sep 2010 19:41:00 +0000

Abstract
High-density lipoprotein-cholesterol (HDL-C) is a continuous inverse cardiovascular risk factor. The mechanisms by which HDLs protect against atherosclerosis are multiple. The major effect is thought to be reverse cholesterol transport, the mechanism by which excess cellular cholesterol is returned to the liver for excretion in the bile.

HDLs also have pleiotropic roles: they decrease inflammation, prevent low-density lipoprotein oxidation, vascular endothelial cell apoptosis and thrombosis, and improve vascular endothelial function. Recent studies suggest that nascent HDL particles are metabolized rapidly and that their components (Apo AI, cholesterol and phospholipids) are rapidly exchanged within lipoprotein classes. There are many causes of HDL-C deficiency. Using Mendelian randomization, several groups have concluded that many genetic forms of HDL deficiency do not increase cardiovascular risk.

This raises the controversial issue of the causality of low HDL-C as a cardiovascular risk factor, rather than a marker of cardiovascular health. This is reflected in the importance of lifestyle in determining HDL-C levels. The treatment of low HDL-C remains controversial, in part because the only currently available effective medication, niacin, is relatively poorly tolerated and outcomes studies on cardiovascular disease prevention are still pending

Alwaili K, Awan Z, Alshahrani A, Genest J.

Cardiovascular Research Laboratories, McGill University Health Centre/Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Quebec, Canada.

Expert Rev Cardiovasc Ther. 2010 Mar;8(3):413-23.

Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein

noreply@blogger.com (Diagnostic Research) — Thu, 28 Jan 2010 18:41:00 +0000

Abstract
Objectives
We previously observed an association between ovarian cancer outcome and statin use and hypothesized lipoproteins have direct effects on ovarian cancer proliferation. Here we investigate the direct effects of low density lipoprotein (LDL) and oxidized LDL (oxLDL) on proliferation and the inhibitory effects of fluvastatin and a liver X receptor (LXR) agonist.

Methods
The effects of LDL, oxLDL, the LXR agonist TO901317, fluvastatin and cisplatin on cellular proliferation were determined using MTT assays. LXR pathway proteins were assayed by immunoblotting. Cytokine expression was determined by antibody array.

Results
Concentrations of oxLDL as small as 0.1 μg/ml stimulated CAOV3 and SKOV3 proliferation, while LDL had no effect. TO901317 inhibited the proliferation of CAOV3, OVCAR3 and SKOV3 cells stimulated by oxLDL. Fluvastatin inhibited oxLDL mediated proliferation of CAOV3 and SKOV3. Cardiotrophin 1 (CT-1) was mitogenic to CAOV3 and SKOV3, was induced by oxLDL, and was reversed by TO901317. OxLDL increased cisplatin IC50s by 3.8 μM and > 60 μM for CAOV3 and SKOV3 cells, respectively. The LXR pathway proteins CD36, LXR, and ABCA1 were expressed in eight ovarian carcinoma cell lines (A2780, CAOV3, CP70, CSOC882, ES2, OVCAR3, SKOV3).

Conclusions
OxLDL reduced ovarian carcinoma cell chemosensitivity and stimulated proliferation. These effects were reversed by LXR agonist or fluvastatin. The LXR agonist also inhibited expression of the ovarian cancer mitogen CT-1. These observations suggest a biologic mechanism for our clinical finding that ovarian cancer survival is associated with statin use. Targeting LXR and statin use may have a therapeutic role in ovarian cancer.

Daniel R. Scolesa, b, , , Xuan Xua, Haimei Wangc, Hang Trana, Barbie Taylor-Hardingb, Andrew Lia, b and Beth Y. Karlana, b

aWomen's Cancer Research Institute and Division of Gynecologic Oncology, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, USA

bDepartment of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

cDivision of Cardiothoracic Surgery, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, USA

Received 17 April 2009. Available online 24 October 2009.

Reconstituted High-Density Lipoprotein Increases Plasma High-Density Lipoprotein Anti-Inflammatory Properties and Cholesterol Efflux Capacity in Patie

noreply@blogger.com (Diagnostic Research) — Tue, 24 Nov 2009 17:46:00 +0000

Abstract
Objectives: Our aim was to investigate the effects of reconstituted high-density lipoprotein (rHDL) infusions on plasma high-density lipoprotein (HDL) anti-inflammatory properties and ex vivo cholesterol efflux in patients with type 2 diabetes.

Background: The anti-inflammatory effects of HDL contribute to protection from cardiovascular events. Individuals with type 2 diabetes are at elevated risk for cardiovascular disease, and typically have low HDL with reduced anti-inflammatory properties.

Methods: Thirteen fasting male patients (mean age 52 years) with type 2 diabetes mellitus received both rHDL (80 mg/kg of apolipoprotein A-I) and a saline placebo on separate occasions in a randomized cross-over design study. Changes in the ability of isolated HDL to influence the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human coronary artery endothelial cells was the main outcome measure. Other outcome measures included expression of the key integrin, CD11b on patient monocytes, adhesiveness of patient neutrophils to fibrinogen, and the ability of plasma to promote cholesterol efflux to THP-1 macrophages.

Results: Four and 72 h post-rHDL infusion, the anti-inflammatory properties of isolated HDL increased in parallel to their concentration in plasma (by up to 25%, p < 0.01). Participants' peripheral blood monocyte CD11b expression and neutrophil adhesion to a fibrinogen matrix was also reduced 72 h post-rHDL, compared with that seen in placebo (p = 0.02). rHDL increased the capacity of plasma to receive cholesterol from THP-1 macrophages by 1 h up to 72 h post-infusion (by 40% to 60%, p < 0.05).

Conclusions: rHDL infusions have significant, potentially atheroprotective effects in individuals with diabetes, including suppression of inflammation and enhancement of cholesterol efflux.

Journal of the American College of Cardiology, Volume 53, Issue 11, Pages 962-971
S. Patel, B. Drew, S. Nakhla, S. Duffy, A. Murphy, P. Barter, K. Rye, J. Chin-Dusting, A. Hoang, D. Sviridov

Effects of sour tea on lipid profile and lipoproteins in patients with type II diabetes

noreply@blogger.com (Diagnostic Research) — Thu, 20 Aug 2009 15:33:00 +0000

OBJECTIVES: There is increasing evidence that intake of sour tea (Hibiscus sabdariffa) has hypoglycemic and hypolipidemic effects and may benefit patients suffering from metabolic disorders such as diabetes. The objective of the present study was to investigate the hypolipidemic effects of sour tea in patients with diabetes and compare them with those of black tea. DESIGN: In this sequential randomized controlled clinical trial, 60 patients with diabetes were recruited and randomly assigned into two groups: sour tea (ST) and black tea (BT). They were instructed to consume sour tea or black tea two times a day for 1 month. OUTCOME MEASURES: Fasting blood samples were taken at the beginning and at the end of the study for evaluation of lipids, lipoproteins, and apoproteins. RESULTS: Fifty-three (53) patients concluded the study. In the ST group, mean of high-density lipoprotein-cholesterol (HDLc) increased significantly (p = 0.002) at the end of the study, whereas changes in apolipoprotein-A1, and lipoprotein (a) were not significant. Also, a significant decrease in the mean of total cholesterol, low density lipoprotein-cholesterol, triglycerides, and Apo-B100 were seen in this group. In the BT group, only HDLc showed significant change (p = 0.002) at the end of the study and changes in the other measures were not statistically significant. CONCLUSIONS: The results of the present study showed that ST has a significant effect on blood lipid profile in patients with diabetes.

Mozaffari-Khosravi H, Jalali-Khanabadi BA, Afkhami-Ardekani M, Fatehi F.
Department of Nutrition, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Lipid treatment guidelines and cardiovascular risk for Aboriginal people in Central Australia

noreply@blogger.com (Diagnostic Research) — Wed, 20 May 2009 19:54:00 +0000

OBJECTIVE: To evaluate the extent to which the current Pharmaceutical Benefits Scheme (PBS) guidelines for patient eligibility for lipid-lowering medication are applicable to Aboriginal people in Central Australia.

DESIGN, SETTING AND PARTICIPANTS: A 10-year cohort study of 659 Aboriginal people who participated in population-based cardiovascular disease (CVD) risk factor surveys in 1995 and who were free of CVD at baseline, for the period from 1995 to 2004-2005 or until first CVD event. Evidence of atherosclerotic CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) was sought from hospital, primary health care and death records. PBS eligibility was assigned according to the current PBS criteria, which were amended in 2006 to include Aboriginal-specific criteria, using participants' baseline (1995) and 10-year follow-up data.

MAIN OUTCOME MEASURES: Proportions of PBS-eligible and PBS-ineligible participants who had CVD events during the study period; sensitivity and specificity of the criteria. RESULTS: Of 42 participants who had CVD events during the study period, 35 were PBS-eligible (incidence, 1130/100 000 person-years; relative risk compared with PBS-ineligible population, 4.87 [95% CI, 2.19-10.80]) and seven were PBS-ineligible. PBS eligibility was associated with older mean age (37 v 32 years) and male sex (48% v 37%), with 50.7% of participants (334/659) meeting eligibility criteria. The mean high-density lipoprotein cholesterol level at baseline was very low in both groups (0.81 v 0.87 mmol/L). The current PBS guidelines have low specificity (52%) in this population, which was found to improve (to 71%-82%) by incorporating additional non-lipid criteria (age and multiple non-lipid risk factors).

CONCLUSION: The current PBS lipid treatment criteria, which include any Aboriginal person with diabetes and less stringent cholesterol thresholds than the previous version, identify a group at very high risk of CVD. Global risk assessment may better identify those at risk.
Onemda VicHealth Koori Health Unit, Centre for Health and Society, School of Population Health, University of Melbourne, Melbourne, VIC, Australia

Risk factors for aortic valve calcification in patients on regular hemodialysis

noreply@blogger.com (Diagnostic Research) — Mon, 18 May 2009 20:53:00 +0000

Urology and Nephrology Clinic, Kragujevac Clinical Center, Kragujevac - Serbia.

Introduction: Aortic valve calcification (AVC) accelerates development of aortic valve stenosis and cardiovascular complications. Hyperphosphatemia is one of the key risk factors for aortic valve calcification.

Aim: The aim of this study was to evaluate the prevalence of AVC in patients on regular hemodialysis and to assess the impact of different factors on its appearance. Method: The study investigated a total of 115 patients treated in the Hemodialysis Department of the Urology and Nephrology Clinic at the Kragujevac Clinical Center in Serbia. The variables investigated were: serum albumin, C-reactive protein (CRP), homocysteine, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), Apolipoprotein A-I (Apo A-I), Apolipoprotein B (Apo B) and lipoprotein (a), calcium, phosphate and parathormone, and calcium-phosphorus product (Ca x P). Patients were evaluated by echocardiography for AVC. Statistical analysis included univariate and multivariate logistic regression analysis.

Results: Univariate regression analysis showed that serum phosphate levels and Ca x P are the most important risk factors for AVC (p<0.001). Multivariate logistic regression analysis revealed that hyperphosphatemia is an independent risk factor for AVC (p<0.001).

Conclusion: Hyperphosphatemia is an independent risk factor for aortic valve calcification.

Risk Stratification of Apolipoprotein B, Apolipoprotein A1, and Apolipoprotein B/AI Ratio on the Prevalence of the Metabolic Syndrome: the ATTICA Stud

noreply@blogger.com (Diagnostic Research) — Tue, 15 Jul 2008 20:28:00 +0000

First Cardiology Clinic, School of Medicine, University of Athens, Greece

We investigated the association of apolipoproteins AI and B in relation to the prevalence of metabolic syndrome in a random sample of cardiovascular disease— free adults from the ATTICA study (1,514 men, aged 18-87 y; 1,528 women, aged 18-89 y). Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of metabolic syndrome was 25% in men and 15% in women (P < .001). Using the area under the Receiver Operation Characteristic curve, apolipoprotein B/AI was the best diagnostic marker of metabolic syndrome, the optimal discriminating cut-off value of this ratio was 0.72 (sensitivity 74%, specificity 67%), and individuals with apolipoprotein B/AI ratio greater than 0.74 had 3.29 times higher odds of having metabolic syndrome (95% confidence interval: 2.56-4.21) after adjusting for potential confounders.

Treatment with an apolipoprotein A-1 mimetic peptide in combination with pravastatin inhibits collagen-induced arthritis

noreply@blogger.com (Diagnostic Research) — Thu, 10 Jul 2008 20:17:00 +0000

To evaluate the therapeutic potential of an apolipoprotein A-1 (apoA-1) mimetic peptide, D-4F, in combination with pravastatin in collagen-induced arthritis (CIA), syngeneic Louvain rats were immunized with type II collagen and randomized to vehicle control, D-4F monotherapy, pravastatin monotherapy, or D-4F + pravastatin combination therapy. Clinical arthritis activity was evaluated and radiographs, type II collagen antibody titers, cytokine/chemokine levels, and HDL function analysis were obtained. There was significant reduction in clinical severity scores in the high and medium dose D-4F + pravastatin groups compared to controls (p ≤ 0.0001). Reduction in erosive disease occurred in the medium/high dose combination groups compared to non-combination groups (p ≤ 0.01). Favorable changes in cytokines/chemokines were noted with treatment, and response to combination D-4F/pravastatin therapy was associated with improvement in HDL's anti-inflammatory properties. Combination D-4F/pravastatin significantly reduced clinical disease activity in CIA, and may have dual therapeutic potential in other autoimmune diseases with increased cardiovascular morbidity and mortality.

ARTICLE

Lipidation of apolipoprotein A-I by ATP-binding cassette transporter (ABC) A1 generates an interaction partner for ABCG1 but not for scavenger recepto

noreply@blogger.com (Diagnostic Research) — Mon, 30 Jun 2008 20:00:00 +0000

The ATP-binding cassette transporters ABCA1 and ABCG1 as well as scavenger receptor BI (SR-BI) mediate the efflux of lipids from macrophages to apolipoprotein A-I (apoA-I) and high density lipoproteins (HDL). We used RNA interference in RAW264.7 macrophages to study the interactions of ABCA1, ABCG1, and SR-BI with lipid-free apoA-I, native and reconstituted HDL with apoA-I:phosphatidylcholine ratios of either 1:40 (rHDL1:40) or 1:100 (rHDL1:100). Knock-down of ABCA1 inhibits the cellular binding at 4 °C of lipid-free apolipoprotein A-I (apoA-I) but not of HDL whereas suppression of ABCG1 or SR-BI reduces the binding of high density lipoproteins (HDL). but not lipid-free apoA-I. The degree of lipidation influences the interactions of rHDL with ABCG1 and SR-BI. Knock-down of ABCG1 inhibits more effectively the binding and cholesterol efflux capacities of lipid-poorer rHDL1:40 whereas knock-down of SR-BI has a more profound effect on the binding and cholesterol efflux capacities of lipid-richer rHDL1:100. Moreover, knock-down of ABCG1 but not SR-BI interferes with the association of lipid-free apoA-I during prolonged incubation at 37 °C. Finally, knock-down of ABCG1 inhibits the binding of initially lipid-free apoA-I which has been preconditioned by cells with high ABCA1 activity. The gained ability of initially lipid-free apolipoprotein A-I (apoA-I) to interact with ABCG1 is accompanied by its shift from electrophoretic pre-β- to -mobility. Taken together, these data suggest that the interaction of lipid-free apoA-I with ABCA1 generates a particle that immediately interacts with ABCG1 but not with SR-BI. Furthermore, the degree of lipidation influences the interaction of HDL with ABCG1 or SR-BI.

Iris Lorenzia, Arnold von Eckardsteina, Silvija Radosavljevica and Lucia Rohrer

ARTICLE

Low diurnal variability of apolipoprotein A1, apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio during normal sleep and after an acute shi

noreply@blogger.com (Diagnostic Research) — Mon, 30 Jun 2008 19:52:00 +0000

Objective
The aim of this study was to study the diurnal variation of the cardiovascular risk markers apolipoprotein A1 and B and apo B/apo A1 ratio.

Design and methods
We have studied the diurnal variation of apolipoprotein A1, apolipoprotein B and apo B/apo A1 ratio during night sleep and the day sleep conditions in seven healthy volunteers (age 22–32 yr). Samples were collected every hour to evaluate the effect of different sampling times on the test results.

Results
The lowest diurnal coefficient of variation (CV) was observed for the apo B/apo A1 ratio, which usually was below 2% but also apolipoprotein A1, apolipoprotein B showed low CV. There were no significant differences between nightsleep and daysleep for any of the studied markers.

Conclusion
Even if there was a diurnal variation for these markers, the variation was very low. Thus, sampling does not have to be restricted to certain times of the day.

ARTICLE

Rosuvastatin selectively stimulates apolipoprotein A-I but not apolipoprotein A-II synthesis in Hep G2 cells

noreply@blogger.com (Diagnostic Research) — Thu, 19 Jun 2008 17:47:00 +0000

Hydroxymethylglutaryl–coenzyme A reductase inhibitors (statins) are extensively used to regulate dyslipidemia and to reduce atherosclerotic cardiovascular disease. In addition to effectively lowering cholesterol and low-density lipoprotein (HDL) levels, rosuvastatin and certain other statins can also increase plasma high-density lipoprotein (HDL) cholesterol modestly. However, the mechanism of action of rosuvastatin on HDL metabolic processes is not understood. Using cultured human hepatoblastoma cells (Hep G2) as an in vitro model system, we assessed the effect of rosuvastatin on apolipoprotein (apo) A-I and apo A-II (the major proteins of HDL) synthesis and HDL catabolic processes. Rosuvastatin dose-dependently increased messenger RNA expression and de novo synthesis of apo A-I but not apo A-II. Rosuvastatin selectively increased the synthesis of HDL particles containing only apo A-I (LP A-I) but not particles containing both apo A-I and A-II (LP A-I + A-II). The HDL3-protein or HDL3-cholesterol ester uptake by Hep G2 cells was not affected by rosuvastatin. The apo A-I–containing particles secreted by rosuvastatin-treated Hep G2 significantly increased cholesterol efflux from fibroblasts. The data indicate that rosuvastatin increases hepatic apo A-I but not apo A-II messenger RNA transcription, thereby selectively increasing the synthesis of functionally active apo A-I–containing HDL particles, which mediate cholesterol efflux from peripheral tissues. We suggest that this mechanism of action of rosuvastatin to increase apo A-I production without apo A-I/HDL removal may result in increased apo A-I turnover that results in accelerated reverse cholesterol transport.

Shucun Qina, b, Takafumi Kogaa, b, Shobha H. Ganjia, b, Vaijinath S. Kamanna, a, b, and Moti L. Kashyap

ARTICLE

Cholesterol is a determinant of the structures of discoidal high density lipoproteins formed by the solubilization of phospholipid membranes by apolip

noreply@blogger.com (Diagnostic Research) — Tue, 10 Jun 2008 21:26:00 +0000

Formation of discoidal high density lipoproteins(rHDL) by Apolipoprotein A-I (apoA-I) mediated solubilization of dimyristoyl phosphatidylcholine (DMPC) multilamellar vesicles (MLV) was dramatically affected by bilayer cholesterol concentration. At a low ratio of DMPC/apoA-I (2 mg DMPC/mg apoA-I, 84/1 mol/mol), sterols (cholesterol, lathosterol, and β-sitosterol) that form ordered lipid phases increase the rate of solubilization similarly, yielding rHDL with similar structures. By changing the temperature and sterol concentration, the rates of solubilization varied almost 3 orders of magnitude; however, the sizes of the rHDL were independent of the rate of their formation and dependent upon the bilayer sterol concentration. At a high ratio of DMPC/apoA-I (10/1 mg DMPC/mg apoA-I, 420/1 mol/mol), changing the temperature and cholesterol concentration yielded rHDL that varied greatly in size, phospholipid/protein ratio, mol% cholesterol, and number of apoA-I molecules per particle. rHDL were isolated that had 2, 4, 6, and 8 molecules of apoA-I per particle, mean diameters of 117, 200, 303, and 396 Å, and a mol% cholesterol that was similar to the original MLV. Kinetic studies demonstrated that the different sized rHDL are formed independently and concurrently. The rate of formation, lipid composition, and three-dimensional structures of cholesterol-rich rHDL is dictated primarily by the original membrane phase properties and cholesterol content. The size speciation of rHDL and probably nascent HDL formed via the activity of the ABCA1 lipid transporter is mechanistically linked to the cholesterol content of the membranes from which they were formed.

Keywords: Reverse cholesterol transport; apoA-I; Cholesterol; High density lipoprotein; Phosphatidylcholine; Microsolubilization

John B. Massey, a, and Henry J. Pownall

ARTICLE

An apolipoprotein A-I gene promoter polymorphism associated with cognitive decline, but not with Alzheimer's disease.

noreply@blogger.com (Diagnostic Research) — Fri, 01 Feb 2008 17:50:00 +0000

BACKGROUND/AIMS: Accumulating biological and epidemiological evidence suggests a close link between cholesterol metabolism and the pathophysiology of Alzheimer's disease (AD).

The observation that the use of statins reduces the risk of Alzheimer's disease sustains this hypothesis. Apolipoprotein A-I (APOA1) is the major component of the high-density lipoproteins , particles involved in reverse cholesterol transport. Therefore, genetic polymorphisms in the gene encoding APOA1 might influence cholesterol metabolism and be a risk factor for AD.

A previous study suggested an impact of a G-->A polymorphism at position -75 bp in the APOA1 gene on the risk for early-onset AD and on the age at onset of the disease. We studied this polymorphism in 3 independent European population samples. METHODS: Genotyping was conducted asdescribed in the previous study.

RESULTS: We were unable to show any impact of this polymorphism on the risk of AD. Conversely, subjects bearing the A allele of this polymorphism were at risk of cognitive decline. CONCLUSION: Our resultssuggest an impact of the G-->A polymorphism at position -75 bp in the APOA1 gene on cognitive impairment, but not on the risk of AD. Copyright (c) 2007 S. Karger AG, Basel.

Helbecque N, Codron V, Cottel D, Amouyel P.
INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France.
Dement Geriatr Cogn Disord. 2008;25(2):97-102. Epub 2007 Dec 10

APOLIPOPROTEIN OF HIGH DENSITY LIPOPROTEIN

noreply@blogger.com (Diagnostic Research) — Wed, 26 Dec 2007 15:21:00 +0000

Apolipoprotein A-I is the major apoprotein of High Density Lipoprotein and is a relatively abundant plasma protein with a concentration of 1.0-1.5 mg/ml. It is a single polypeptide chain with 243 amino acid residues of known primary amino acid sequence (Brewer et al., 1978). Apolipoprotein A-I is a cofactor for LCAT (606967), which is responsible for the formation of most cholesteryl esters in plasma. apoA-I also promotes efflux of cholesterol from cells. The liver and small intestine are the sites of synthesis of apoA-I . The primary translation product of the APOA1 gene contains both a pre and a pro segment, and posttranslational processing of apoA-I may be involved in the formation of the functional plasma apoA-I isoproteins. Dayhoff (1976) pointed to sequence homologies of A-I, A-II , C-I , and C-III .

Apo A-I is a peptide of molecular weight 28,300 that is a major component of HDLs and is also found in chylomicrons .