Cholesterol The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia Thu, 06 Jul 2017 09:04:06 +0000 Valvular heart disease frequently occurs as a consequence of premature atherosclerosis in individuals with familial hypercholesterolemia (FH). Studies have primarily focused on aortic valve calcification in heterozygous FH, but there is paucity of data on the incidence of valvular disease in homozygous FH. We performed echocardiographic studies in 33 relatively young patients (mean age: 26 years) with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis) to look for subclinical valvulopathy. Twenty-one patients had evidence of valvulopathy of the aortic or mitral valves, while seven subjects showed notable mitral regurgitation. Older patients were more likely to have aortic valve calcification (>21 versus ≤21 years: 59% versus 12.5%; = 0.01) despite lower LDL levels at the time of the study (385 versus 513 mg/dL; = 0.016). Patients with valvulopathy were older and had comparable LDL levels and a lower carotid intima-media thickness. Our data suggests that, in homozygous FH patients, valvulopathy is present across a wide age spectrum and LDL levels and is less likely to be influenced by lipid-lowering treatment. Echocardiographic studies that focused on aortic root thickening and stenosis and regurgitation are thus likely an effective modality for serial follow-up of subclinical valvular heart disease. Akl C. Fahed, Kamel Shibbani, Rabih R. Andary, Mariam T. Arabi, Robert H. Habib, Denis D. Nguyen, Fady F. Haddad, Elie Moubarak, Georges Nemer, Sami T. Azar, and Fadi F. Bitar Copyright © 2017 Akl C. Fahed et al. All rights reserved. Identification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice Wed, 31 May 2017 08:23:59 +0000 DDD/Sgn mice have significantly higher plasma lipid concentrations than C57BL/6J mice. In the present study, we performed quantitative trait loci (QTL) mapping for plasma total-cholesterol (CHO) and triglyceride (TG) concentrations in reciprocal F2 male intercross populations between the two strains. By single-QTL scans, we identified four significant QTL on chromosomes (Chrs) 1, 5, 17, and 19 for CHO and two significant QTL on Chrs 1 and 12 for TG. By including cross direction as an interactive covariate, we identified separate significant QTL on Chr 17 for CHO but none for TG. When the large phenotypic effect of QTL on Chr 1 was controlled by composite interval mapping, we identified three additional significant QTL on Chrs 3, 4, and 9 for CHO but none for TG. QTL on Chr 19 was a novel QTL for CHO and the allelic effect of this QTL significantly differed between males and females. Whole-exome sequence analysis in DDD/Sgn mice suggested that Apoa2 and Acads were the plausible candidate genes underlying CHO QTL on Chrs 1 and 5, respectively. Thus, we identified a multifactorial basis for plasma lipid concentrations in male mice. These findings will provide insight into the genetic mechanisms of plasma lipid metabolism. Jun-ichi Suto and Misaki Kojima Copyright © 2017 Jun-ichi Suto and Misaki Kojima. All rights reserved. Cholesterol Levels in Genetically Determined Familial Hypercholesterolaemia in Russian Karelia Tue, 28 Mar 2017 00:00:00 +0000 Familial hypercholesterolaemia (FH) is a rare disease that tends to be diagnosed lately. In Russia, the genetic and phenotypic characteristics of the disease are not well defined. We investigated 102 patients with definite FH. In 52 of these patients (50.9%) genetic analysis was performed, revealing pathogenic mutations of the low density lipoprotein (LDL) receptor gene in 22 patients. We report here five mutations of the LDL receptor gene found in the Karelian FH sample for the first time. The detection rate of mutations in definite FH patients was 42.3%. Two groups of patients with a definite diagnosis of FH according to the Dutch Lipid Clinic Network criteria were compared: the first group had putatively functionally important LDL receptor gene mutations, while in the second group LDL receptor gene mutations were excluded by single-strand conformation polymorphism analysis. Total and LDL cholesterol levels were higher in the group with LDL receptor mutations compared to the mutation-free population. The frequency of mutations in patients with LDL cholesterol > 6.5 mmol/L was more than 3 times higher than that in patients with LDL < 6.5 mmol/L. Total and LDL cholesterol levels and the frequency of coronary heart disease and myocardial infarction were higher in the group with definite FH compared to groups with probable and possible FH. Cholesterol figures in FH patients of different age and sex from the Karelian population were comparable. V. A. Korneva, T. Yu. Kuznetsova, T. Yu. Bogoslovskaya, D. S. Polyakov, V. B. Vasilyev, A. V. Orlov, and M. Yu. Mandelshtam Copyright © 2017 V. A. Korneva et al. All rights reserved. The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies Wed, 22 Feb 2017 00:00:00 +0000 The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded. Frans Stellaard and Dieter Lütjohann Copyright © 2017 Frans Stellaard and Dieter Lütjohann. All rights reserved. Banana Blossom (Musa acuminate Colla) Incorporated Experimental Diets Modulate Serum Cholesterol and Serum Glucose Level in Wistar Rats Fed with Cholesterol Wed, 30 Nov 2016 14:08:24 +0000 Hypocholesterolaemic and hypoglycaemic effect of banana blossom were studied in high-cholesterol fed rats. Experimental groups were fed for 4 weeks, with casein as the basal diet (CN), in comparison with two diets containing 0.5% cholesterol (CD) and 0.5% cholesterol + 21% banana blossom powder (CDB). Serum total cholesterol, non-HDL-cholesterol level, and serum glucose concentrations were lower in CDB fed group compared with CD fed group. Lower serum cholesterol and glucose level () in CDB fed group were followed by higher faecal weight, caecal weight, caecal Lactobacilli, and Bifidobacteria population in CDB fed group compared to CD diet fed group. Lower serum AST level in banana blossom fed rats showed the reduction in oxidative stress induced by high cholesterol diet. Based on these data, it could be speculated that banana blossom incorporated experimental diets may modulate the hypocholesterolaemic and hypoglycaemic responses in Wistar rats. Ruvini Liyanage, Saranya Gunasegaram, Rizliya Visvanathan, Chathuni Jayathilake, Pabodha Weththasinghe, Barana Chaminda Jayawardana, and Janak Kamil Vidanarachchi Copyright © 2016 Ruvini Liyanage et al. All rights reserved. In Vivo Antihypercholesterolemic Potential of Swietenia mahagoni Leaf Extract Thu, 13 Oct 2016 14:45:03 +0000 The present investigation aims to evaluate antihypercholesterolemic potential of Swietenia mahagoni leaf aqueous extract (MAE) in diet-induced hypercholesterolemic rat model. In the study, Wistar albino rats (170–220 g) were segregated into 5 groups; all the groups except normal control group were given high fat diet to induce hypercholesterolemia. After induction of cholesterolemia, normal control and positive control groups were treated with saline, statin group was treated with atorvastatin, and remaining two groups received MAE in two doses (250 and 500 mg kg−1 BW) for a treatment period of one month. After the treatment period, weight of rats was recorded and they were anesthetized and decapitated. Blood samples were taken and triglycerides, total cholesterol, LDL-C, HDL-C, malondialdehyde (MDA), and urea were determined. Liver and kidney were taken for the estimation of lipid peroxides. The positive control group showed higher values of triglycerides ( mg/dL), total cholesterol ( mg/dL), LDL-C ( mg/dL), MDA, and bile acid content when compared to a normal control group (triglycerides ( mg/dL), total cholesterol ( mg/dL), and LDL-C ( mg/dL)). Treatment with MAE decreased the cholesterol levels, HDL-C, ALT, AST, and bilirubin levels and the effect was dependent on the dose. The results of this study indicated that MAE possesses hypolipidemic potential and thus could be useful in the treatment of hypercholesterolemic condition. Naveen Yelaware Puttaswamy and Asna Urooj Copyright © 2016 Naveen Yelaware Puttaswamy and Asna Urooj. All rights reserved. Trends of Prevalence of Uncontrolled Risk Factors for Cerebrocardiovascular Disease: Southern Italy from 1988/9 to 2008/9 Sun, 24 Apr 2016 08:59:48 +0000 The aim of this study was to determine the trends of cardiovascular risk factor prevalence between 1988/9 and 2008/9 in the 25–74-year-old population in an area of Southern Italy. We compared three cross-sectional studies conducted in random population samples, in 1988/9, 1998/9, and 2008/9 in Salerno, Italy. The methodology of data collection (lipid profile, systolic and diastolic blood pressure, glycaemia, and smoking) and conducting tests which the population underwent during the three phases was standardized and comparable. Prevalence of diabetes, hypertension, hypercholesterolemia, and smoking was calculated and standardized for age. A total of 3491 subjects were included. From 1988/9 to 2008/9, in males, the prevalence of all four risk factors was reduced. In women, there was a clear reduction of hypertension, a similar prevalence of hypercholesterolemia, and an increase of smoking and diabetes. In the area of Salerno, our data confirm that the global prevalence of the major risk factors is decreasing in men, but their absolute values are still far from optimization. In women, diabetes and smoking showed a negative trend, therefore requiring targeted interventions. These data are now used as a base for executive targeted programs to improve prevention of cardiovascular disease in our community. Vincenzo Capuano, Norman Lamaida, Ernesto Capuano, Rocco Capuano, Eduardo Capuano, and Gianfranco Mazzotta Copyright © 2016 Vincenzo Capuano et al. All rights reserved. Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats Thu, 14 Apr 2016 07:58:11 +0000 The present study was carried out to investigate the antidiabetic and antihyperlipidemic properties of hydroalcoholic extract of Peganum harmala in streptozotocin-induced diabetic male rats. In an experimental study, 64 normal Wistar albino male rats (200–230 g) were randomly divided into 8 groups. Control and diabetic rats were treated with normal saline and three different doses (30, 60, and 120 mg/kg) of hydroalcoholic extract of Peganum harmala seeds for 4 weeks orally. At the end of treatment, blood samples were taken and glucose, triglycerides, total cholesterol, LDL-c, HDL-c, malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, GGT, bilirubin, and glycosylated hemoglobin () were determined. STZ-induced diabetic rats showed significant changes in the values of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and in comparison with normal rats. Administration of the extract to diabetic rats resulted in a remarkable decrease in glucose, lipid profiles, MDA, ALT, AST, GGT, bilirubin, and levels and increase in TAC relative to diabetic group. The results of this study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities and could be useful in treatment of diabetes. Gholamreza Komeili, Mohammad Hashemi, and Mohsen Bameri-Niafar Copyright © 2016 Gholamreza Komeili et al. All rights reserved. Cholesterol Lowering Effect of Plant Stanol Ester Yoghurt Drinks with Added Camelina Oil Sun, 21 Feb 2016 12:30:04 +0000 The aim of this study was to investigate the effects of yoghurt minidrinks containing two doses of plant stanol ester either with or without added camelina oil on the serum cholesterol levels in moderately hypercholesterolemic subjects. In this randomised, double-blind, parallel group study, 143 subjects consumed a 65 mL minidrink together with a meal daily for four weeks. The minidrink contained 1.6 or 2.0 grams of plant stanols with or without 2 grams of alpha-linolenic acid-rich camelina oil. The placebo minidrink did not contain plant stanols or camelina oil. All plant stanol treated groups showed statistically significant total, LDL, and non-HDL cholesterol lowering relative to baseline and relative to placebo. Compared to placebo, LDL cholesterol was lowered by 9.4% () and 8.1% () with 1.6 g and 2 g plant stanols, respectively. With addition of Camelina oil, 1.6 g plant stanols resulted in 11.0% () and 2 g plant stanols in 8.4% () reduction in LDL cholesterol compared to placebo. In conclusion, yoghurt minidrinks with plant stanol ester reduced serum LDL cholesterol significantly and addition of a small amount of camelina oil did not significantly enhance the cholesterol lowering effect. This trial was registered with NCT02628990. Pia Salo and Päivi Kuusisto Copyright © 2016 Pia Salo and Päivi Kuusisto. All rights reserved. Lipid Lowering Effects of Hydroalcoholic Extract of Anethum graveolens L. and Dill Tablet in High Cholesterol Fed Hamsters Mon, 28 Dec 2015 12:56:32 +0000 Objective. This study was aimed to determine the effect of Anethum graveolens extract and Anethum graveolens (dill) tablet on lipid profile, liver enzymes, and gene expression and enzymatic activity of HMG-CoA reductase in high cholesterol fed hamsters. Materials and Methods. Golden Syrian male hamsters (130 ± 10 g) were randomly divided into 6 groups () and received daily the following: group 1 received chow + 2% cholesterol + 0.5% cholic acid (HCD), groups 2 and 3 received HCD diet plus 100 and 200 mg/kg hydroalcoholic extract of dill, respectively, and groups 4 and 5 received HCD diet plus 100 and 200 mg/kg dill tablet, respectively. Group 6 received only chow. After 1 month feeding serum biochemical factors were determined. HMG-CoA reductase mRNA level was measured (real-time PCR) and its activity was determined spectrophotometrically. Results. Compared with hypercholesterolemic group 1, lipid profile, blood glucose, and liver enzymes significantly decreased in all dill tablet or dill extract treated groups (). The changes in HMG-CoA reductase gene expression level and enzyme activity significantly reduced in animals that received 200 mg/kg of extract or tablet. Conclusion. Dill extract and dill tablet showed potential hypocholesterolemic properties in hamsters by inhibition of HMG-CoA reductase activity. Ebrahim Abbasi Oshaghi, Iraj Khodadadi, Massoud Saidijam, Reza Yadegarazari, Nooshin Shabab, Heidar Tavilani, and Mohamad Taghi Goodarzi Copyright © 2015 Ebrahim Abbasi Oshaghi et al. All rights reserved. Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome Tue, 15 Dec 2015 10:04:05 +0000 ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran) during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75%) compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (). Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression. Zahra Tavoosi, Hemen Moradi-Sardareh, Massoud Saidijam, Reza Yadegarazari, Shiva Borzuei, Alireza Soltanian, and Mohammad Taghi Goodarzi Copyright © 2015 Zahra Tavoosi et al. All rights reserved. Dysfunctional High-Density Lipoprotein: An Innovative Target for Proteomics and Lipidomics Sun, 08 Nov 2015 12:29:57 +0000 High-Density Lipoprotein-Cholesterol (HDL-C) is regarded as an important protective factor against cardiovascular disease, with abundant evidence of an inverse relationship between its serum levels and risk of cardiovascular disease, as well as various antiatherogenic, antioxidant, and anti-inflammatory properties. Nevertheless, observations of hereditary syndromes featuring scant HDL-C concentration in absence of premature atherosclerotic disease suggest HDL-C levels may not be the best predictor of cardiovascular disease. Indeed, the beneficial effects of HDL may not depend solely on their concentration, but also on their quality. Distinct subfractions of this lipoprotein appear to be constituted by specific protein-lipid conglomerates necessary for different physiologic and pathophysiologic functions. However, in a chronic inflammatory microenvironment, diverse components of the HDL proteome and lipid core suffer alterations, which propel a shift towards a dysfunctional state, where HDL-C becomes proatherogenic, prooxidant, and proinflammatory. This heterogeneity highlights the need for further specialized molecular studies in this aspect, in order to achieve a better understanding of this dysfunctional state; with an emphasis on the potential role for proteomics and lipidomics as valuable methods in the search of novel therapeutic approaches for cardiovascular disease. Juan Salazar, Luis Carlos Olivar, Eduardo Ramos, Mervin Chávez-Castillo, Joselyn Rojas, and Valmore Bermúdez Copyright © 2015 Juan Salazar et al. All rights reserved. The Effect of Elevated Triglycerides on the Onset and Progression of Coronary Artery Disease: A Retrospective Chart Review Wed, 04 Nov 2015 11:57:05 +0000 Background. The American College of Cardiology and American Heart Association did not indicate a correlation between treating hypertriglyceridemia and reducing cardiovascular events. Objective. This study investigated whether patients with hypertriglyceridemia were more prone to worse outcomes during cardiac catheterization. Methods. Data collected over a one-year period analyzed lipid panels obtained at the time of cardiac catheterization. Triglyceride levels were categorized into three groups: <150 mg/dL, 150 mg/dL–300 mg/dL, and >300 mg/dL. Controlled variables included age, gender, the presence of hypertension, diabetes, hyperlipidemia, and history of coronary artery disease. Results. Subjects with a triglyceride level <150 mg/dL have a 54% likelihood of being treated medically compared to 38% and 41% in the 150 mg/dL–300 mg/dL and >300 mg/dL groups, respectively (). Subjects with a triglyceride level >300 mg/dL have a 20% percent chance of being treated with a coronary artery bypass graft compared to 12% and 15% in the <150 mg/dL and 150 mg/dL–300 mg/dL groups, respectively (). Subjects with a triglyceride level between 150 and 300 mg/dL have a 44% percent of being treated with a percutaneous coronary intervention compared to 34% and 43% in the <150 mg/dL and >300 mg/dL groups, respectively (). Conclusion. Hypertriglyceridemia was associated with worse outcomes in percutaneous coronary intervention or surgery. Deepu Daniel, Patrick Hardigan, Asif Jawaid, Rohit Bhandari, and Mithun Daniel Copyright © 2015 Deepu Daniel et al. All rights reserved. Optimal Use of Plant Stanol Ester in the Management of Hypercholesterolemia Mon, 12 Oct 2015 13:27:37 +0000 Plant stanol ester is a natural compound which is used as a cholesterol-lowering ingredient in functional foods and food supplements. The safety and efficacy of plant stanol ester have been confirmed in more than 70 published clinical studies and the ingredient is a well-established and widely recommended dietary measure to reduce serum cholesterol. Daily intake of 2 g plant stanols as plant stanol ester lowers LDL-cholesterol by 10%, on average. In Europe, foods with added plant stanol ester have been on the market for 20 years, and today such products are also available in many Asian and American countries. Despite the well-documented efficacy, the full potential in cholesterol reduction may not be reached if plant stanol ester is not used according to recommendations. This review therefore concentrates on the optimal use of plant stanol ester as part of dietary management of hypercholesterolemia. For optimal cholesterol lowering aiming at a lower risk of cardiovascular disease, plant stanol ester should be used daily, in sufficient amounts, with a meal and in combination with other recommended dietary changes. Susanna Rosin, Ilkka Ojansivu, Aino Kopu, Malin Keto-Tokoi, and Helena Gylling Copyright © 2015 Susanna Rosin et al. All rights reserved. Serum Cholesterol Reduction Efficacy of Biscuits with Added Plant Stanol Ester Wed, 11 Mar 2015 06:24:36 +0000 This study’s aim was to test the low-density lipoprotein cholesterol- (LDL-c-) lowering efficacy of biscuits containing 2 g of plant stanols, which corresponded to 3.4 g of plant stanol esters. The biscuit is a new food format that can be consumed as a snack. In a double-blind, placebo-controlled parallel design study, 119 mildly to moderately hypercholesterolemic volunteers were randomized to plant stanol or control groups. Subjects were comparable in age, gender, lipid profiles, and body mass index. They consumed a control biscuit once a day for a two-week period, followed by a four-week intervention period that either had a plant stanol ester biscuit or a control. During the habitual diet, one biscuit per day was consumed at any time that subjects wished. Serum lipid profiles were measured at the first day of run-in, at baseline, and at the study’s end. Compared to the control, the total cholesterol (TC), LDL-c, and the LDL-to-high-density lipoprotein (LDL/HDL) ratio had serum reductions of 4.9%, 6.1%, and 4.3%, respectively, and were observed after 4 weeks of biscuit consumption with added plant stanols (P < 0.05). A significantly higher reduction in LDL-c (8.9%) and LDL/HDL ratio (11.4%) was measured in those taking a plant stanol biscuit with a meal compared to those who consumed a plant stanol biscuit without other food. In conclusion, incorporating plant stanols into a biscuit is an attractive, convenient, and acceptable way to modestly lower elevated cholesterol concentrations. For optimal efficacy, biscuits should be consumed with a meal as part of a healthy diet. Wantanee Kriengsinyos, Ajima Wangtong, and Surat Komindr Copyright © 2015 Wantanee Kriengsinyos et al. All rights reserved. Nonselective Mevalonate Kinase Inhibitor as a Novel Class of Antibacterial Agents Mon, 26 Jan 2015 14:04:55 +0000 Introduction. There are a few evidences about targeting isoprenoids biosynthesis pathway in bacteria for finding new antibiotics. This study was conducted to assess antibacterial effects of vanadyl sulfate (VS), one of the mevalonate kinase inhibitors to find a new target for killing bacteria. Materials and Methods. Antibacterial effect of VS alone and in combination with glycine or EDTA was assessed on Escherichia coli and Pseudomonas aeruginosa as Gram-negative and Staphylococcus aureus and Enterococcus faecalis as Gram-positive bacteria using serial dilution method and minimum inhibitory concentrations (MICs) identified. Result. MICs for S. aureus and E. coli were 4 and 8 mg/mL, respectively. VS could not affect the growth of two other bacteria. However, VS in combination with glycine not only inhibited the growth of E. faecalis and P. aeruginosa, but also reduced MICs for VS-sensitive bacteria (S. aureus and E. coli). EDTA could reduce MIC for E. coli and P. aeruginosa. Conclusion. VS could inhibit the growth of S. aurous and E. coli, and adding glycine or EDTA improved VS antibacterial activity presumably via instability of the cell wall and enhanced transport of VS through bacterial cell wall. Inhibition of the isoprenoid pathway might provide new tools to overcome bacterial resistance. Mohammad Gharehbeglou, Ghasem Arjmand, Mohammad Reza Haeri, and Mohammad Khazeni Copyright © 2015 Mohammad Gharehbeglou et al. All rights reserved. Severe/Extreme Hypertriglyceridemia and LDL Apheretic Treatment: Review of the Literature, Original Findings Tue, 16 Dec 2014 00:10:03 +0000 Hypertriglyceridemia (HTG) is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase the risk of premature coronary artery disease. HTG may also be due to genetic factors (called primary HTG) and particularly the severe/extreme HTG (SEHTG), which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG caused by autoimmune disease. This review considers the causes of SEHTG, and their management including treatment with low density lipoprotein apheresis and analyzes the original findings. Olga Diakoumakou, Georgios Hatzigeorgiou, Nikos Gontoras, Maria Boutsikou, Vana Kolovou, Sophie Mavrogeni, Vassiliki Giannakopoulou, and Genovefa D. Kolovou Copyright © 2014 Olga Diakoumakou et al. All rights reserved. Effects of Atorvastatin on Resting and Peak Exercise Blood Pressure among Normotensive Men and Women Tue, 18 Nov 2014 06:48:55 +0000 Statins are the most widely prescribed and effective medication for reducing low density lipoprotein cholesterol. Statins may also lower resting blood pressure (BP); however, results are inconsistent. We sought to determine if the maximum dose of atorvastatin reduces resting BP and the peak systolic BP (SBP) achieved on a graded exercise stress test (GEST) among a large sample of 419 healthy men (48%) and women (52%). Subjects (419,  yr) were double-blinded and randomized to 80 mgd−1 of atorvastatin () or placebo () for 6 mo. Among the total sample, there were no differences in resting BP (SBP, ; diastolic BP [DBP], ; mean arterial pressure (); or peak SBP on a GEST ()) over 6 mo, regardless of drug treatment group. However, among women on atorvastatin, resting SBP/DBP ( mmHg,  mmHg, ) and peak SBP on a GEST ( mmHg, ) were lower versus men. Atorvastatin lowered resting BP 3-4 mmHg and peak SBP on a GEST ~7 mmHg more among women than men over 6 mo of treatment. The inconsistent findings regarding the antihypertensive effects of statins may be partially explained by not accounting for sex effects. Amanda L. Zaleski, Marianne L. Mentch, Linda S. Pescatello, Beth A. Taylor, Jeffrey A. Capizzi, Adam S. Grimaldi, Priscilla M. Clarkson, Stephanie A. Moeckel-Cole, Stuart R. Chipkin, Justin Keadle, Charles Michael White, and Paul D. Thompson Copyright © 2014 Amanda L. Zaleski et al. All rights reserved. Association of the Total Cholesterol Content of Erythrocyte Membranes with the Severity of Disease in Stable Coronary Artery Disease Mon, 20 Oct 2014 13:08:10 +0000 Increasing evidence suggests that erythrocytes may participate in atherogenesis. We sought to investigate whether the total cholesterol content of erythrocyte membranes (CEM) is significantly different in patients with stable coronary artery disease (CAD) compared to patients with nonsignificant coronary stenosis and determine the correlation between CEM and the severity of coronary stenosis. Methods. The population included 144 patients, undergoing clinically indicated coronary angiography. The severity of coronary stenosis was scored after coronary angiography and patients were divided into two groups; the -stenosis group (CAD patients, ) had a significant stenosis indicated by coronary angiography and the second group, -stenosis (), had nonsignificant coronary stenosis. Lipid parameters were determined by routine laboratory methods. CEM was measured using an enzymatic assay, and protein content was assessed by the modified Lowry method. Results. The mean of CEM levels was higher () in stable CAD patients (137.2 µg/mg of membrane protein) compared with -stenosis patients (110.0 µg/mg of membrane protein). The coronary artery scores were correlated positively with CEM levels (, ). Conclusion. CEM levels are positively associated with the severity of CAD, meaning that CEM might contribute to the development of CAD. Gholamreza Namazi, Morteza Pourfarzam, Sabieh Jamshidi Rad, Ahmad Movahedian Attar, Nizal Sarrafzadegan, Masoumeh Sadeghi, and Parastoo Asa Copyright © 2014 Gholamreza Namazi et al. All rights reserved. A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene Tue, 19 Aug 2014 12:02:46 +0000 Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from in vitro, in vivo, and human studies. Out of a total of 233 nsSNPs, 80 (34.33%) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44%) rare variants resulted highly deleterious with a probability >0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them. A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2. Francisco R. Marín-Martín, Cristina Soler-Rivas, Roberto Martín-Hernández, and Arantxa Rodriguez-Casado Copyright © 2014 Francisco R. Marín-Martín et al. All rights reserved. Effects of Securigera securidaca Extract on Lipolysis and Adipogenesis in Diabetic Rats Sun, 03 Aug 2014 06:35:57 +0000 Diabetes mellitus is associated with dysregulation of adipose tissue metabolism and increased level of serum lipids. In our previous work we found that Securigera securidaca decreases cholesterol level in blood of diabetic rats. The present study was carried out to further investigate the effects of this plant on lipid metabolism, lipolysis, and adipogenesis, in diabetic rats. Female Wistar rats were rendered diabetic by intraperitoneal injection of streptozotocin. Retroperitoneal adipose tissue was removed from diabetic animals after seven days of streptozotocin injection. Effect of hydroalcoholic extract of S. securidaca seeds (100–800 μg/mL) on adipose tissue lipolysis was evaluated in ex vivo condition. Also, to evaluate adipogenesis, preadipocytes were isolated from adipose tissue and differentiated to adipocytes in the presence of the extract. The extract at concentration of 800 μg/mL decreased both basal and catecholamine-stimulated lipolysis . Incubation of differentiating preadipocytes with 800 μg/mL of S. securidaca extract decreased intracellular lipid droplet accumulation as evaluated with Oil Red O staining . The extract even at high concentrations had no effect on viability of preadipocytes. In conclusion, S. securidaca decreases lipolysis and adipogenesis without cytotoxicity, which makes it a good candidate for management of dyslipidemia and reduction of cardiovascular risks in diabetes. Ahmad Ghorbani, Reyhaneh Moradi Marjaneh, Ziba Rajaei, and Mousa-Al-Reza Hadjzadeh Copyright © 2014 Ahmad Ghorbani et al. All rights reserved. Validation of the Friedewald Formula in Patients with Metabolic Syndrome Thu, 06 Feb 2014 11:26:58 +0000 Currently, the Friedewald formula (FF) is the main method for evaluating low-density lipoprotein cholesterol (LDL-c). Recently, many limitations have emerged regarding its use, including patients with triglyceride levels ≥400 mg/dL, diabetes mellitus, and kidney or hepatic chronic diseases. We analyzed the use of the FF in patients with metabolic syndrome. We selected patients with known metabolic syndrome that fulfilled the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report and excluded patients with triglyceride levels ≥400 mg/dL and chronic liver and/or kidney disease. Using direct assays, we measured total cholesterol, high-density lipoprotein cholesterol, triglycerides, and LDL-c. Then, LDL-c was estimated using the FF and compared with the LDL-c by direct assay. The sample size was 135 patients. Using the FF, the mean LDL-c value was  mg/dL; it was  mg/dL by direct assay. The correlation coefficient between these two methods was 0.89, with statistical significance . There were no significant differences between the patients with triglyceride levels >150 mg/dL . In conclusion, FF is a good method for estimating LDL-c in patients with metabolic syndrome. José Knopfholz, Caio César Diniz Disserol, Andressa Jardim Pierin, Fernanda Letícia Schirr, Larissa Streisky, Lilian Lumi Takito, Patrícia Massucheto Ledesma, José Rocha Faria-Neto, Marcia Olandoski, Claudio Leinig Pereira da Cunha, and Antonio Milton Bandeira Copyright © 2014 José Knopfholz et al. All rights reserved. The Influence of an Obesogenic Diet on Oxysterol Metabolism in C57BL/6J Mice Wed, 05 Feb 2014 11:24:28 +0000 Our current understanding of oxysterol metabolism during different disease states such as obesity and dyslipidemia is limited. Therefore, the aim of this study was to determine the effect of diet-induced obesity on the tissue distribution of various oxysterols and the mRNA expression of key enzymes involved in oxysterol metabolism. To induce obesity, male C57BL/6J mice were fed a high fat-cholesterol diet for 24 weeks. Following diet-induced obesity, plasma levels of 4β-hydroxycholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 27-hydroxycholesterol were significantly () increased. In the liver and adipose tissue of the obese mice, 4β-hydroxycholesterol was significantly () increased, whereas 27-hydroxycholesterol was increased only in the adipose tissue. No significant changes in either hepatic or adipose tissue mRNA expression were observed for oxysterol synthesizing enzymes 4β-hydroxylase, 27-hydroxylase, or 7α-hydroxylase. Hepatic mRNA expression of SULT2B1b, a key enzyme involved in oxysterol detoxification, was significantly () elevated in the obese mice. Interestingly, the appearance of the large HDL1 lipoprotein was observed with increased oxysterol synthesis during obesity. In diet-induced obese mice, dietary intake and endogenous enzymatic synthesis of oxysterols could not account for the increased oxysterol levels, suggesting that nonenzymatic cholesterol oxidation pathways may be responsible for the changes in oxysterol metabolism. Joshua S. Wooten, Huaizhu Wu, Joe Raya, Xiaoyuan Dai Perrard, John Gaubatz, and Ron C. Hoogeveen Copyright © 2014 Joshua S. Wooten et al. All rights reserved. Short-Term Effect of Pitavastatin Treatment on Glucose and Lipid Metabolism and Oxidative Stress in Fasting and Postprandial State Using a Test Meal in Japanese Men Tue, 10 Dec 2013 14:00:11 +0000 Introduction. The objective of this study was to clarify how pitavastatin affects glucose and lipid metabolism, renal function, and oxidative stress. Methods. Ten Japanese men (average age of 33.9 years) were orally administered 2 mg of pitavastatin for 4 weeks. Postprandial glucose, lipoprotein metabolism, and oxidative stress markers were evaluated at 0 and 4 weeks of pitavastatin treatment (2 mg once daily) with a test meal consisting of total calories: 460 kcal, carbohydrates: 56.5 g (226 kcal), protein: 18 g (72 kcal), lipids: 18 g (162 kcal), and NaCl: 1.6 g. Metabolic parameters were measured at 0, 60, and 120 minutes after test meal ingestion. Results. After administration of pitavastatin, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, arachidonic acid, insulin, and adjusted urinary excretion of uric acid decreased, whereas creatinine clearance () and uric acid clearance () increased. And postprandial versus fasting urine 8-hydroxydeoxyguanosine remained unchanged, while postprandial versus fasting isoprostane decreased after pitavastatin treatment. Next, we compared postprandial glucose and lipid metabolism after test meal ingestion before and after pitavastatin administration. Incremental areas under the curve significantly decreased for triglycerides () and remnant-like particle cholesterol (), while those for apolipoprotein E (apoE), glucose, insulin, and high-sensitivity C-reactive protein remained unchanged. Conclusion. Pitavastatin improves postprandial oxidative stress along with hyperlipidemia. Hirokazu Kakuda, Junji Kobayashi, Mio Nakato, and Noboru Takekoshi Copyright © 2013 Hirokazu Kakuda et al. All rights reserved. APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism Mon, 09 Dec 2013 10:12:39 +0000 Objectives. This study aims to analysis the relationship between c.-492T>C polymorphism in APOA2 gene and the risk for obesity in a sample of Egyptian adolescents and investigates its effect on body fat distribution and lipid metabolism. Material and Methods. A descriptive, cross-sectional study was conducted on 303 adolescents. They were 196 obese and 107 nonobese, aged 16–19 years old. Variables examined included body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), systolic and diastolic blood pressure (BP), body fat percentage (BF%), abdominal visceral fat layer, and dietary intake. Abdominal visceral fat thickness was determined by ultrasonography. The polymorphism in the APOA2 c.-492T>C was analyzed by PCR amplification. Results. Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases compared to nonobese. After multivariate adjustment, waist, BF% and visceral adipose layer, food consumption, and HDL-C were significantly higher in homozygous allele CC carriers than TT+TC carriers. Conclusions. Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue and serum HDL-C. Moreover, the study shows association between the APOA2 c.-492T>C polymorphism and food consumption. Moushira Erfan Zaki, Khalda Sayed Amr, and Mohamed Abdel-Hamid Copyright © 2013 Moushira Erfan Zaki et al. All rights reserved. Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis Mon, 07 Oct 2013 09:41:51 +0000 The endothelium is the primary target for biochemical or mechanical injuries caused by the putative risk factors of atherosclerosis. Endothelial dysfunction represents the ultimate link between atherosclerotic risk factors that promote atherosclerosis. HDL-C is thought to exert at least some parts of its antiatherogenic facilities via stimulating endothelial NO production, nearby inhibiting oxidative stress and inflammation. HDL-C is capable of opposing LDL’s inductive effects and avoiding the ox-LDL’s inhibition of eNOS. Paraoxonase 1 (PON1) is an HDL-associated enzyme esterase which appears to contribute to the antioxidant and antiatherosclerotic capabilities of HDL-C. “Healthy HDL,” namely the particle that contains the active Paraoxonase 1, has the power to suppress the formation of oxidized lipids. “Dysfunctional HDL,” on the contrary, has reduced Paraoxonase 1 enzyme activity and not only fails in its mission but also potentially leads to greater formation of oxidized lipids/lipoproteins to cause endothelial dysfunction. The association of HDL-C PON1 and endothelial dysfunction depends largely on the molecules with exact damaging effect on NO synthase coupling. Loss of nitric oxide bioavailability has a pivotal role in endothelial dysfunction preceding the appearance of atherosclerosis. Analyses of HDL-C and Paraoxonase1 would be more important in the diagnosis and treatment of atherosclerosis in the very near future. Esin Eren, Necat Yilmaz, and Ozgur Aydin Copyright © 2013 Esin Eren et al. All rights reserved. Low-Fat Nondairy Minidrink Containing Plant Stanol Ester Effectively Reduces LDL Cholesterol in Subjects with Mild to Moderate Hypercholesterolemia as Part of a Western Diet Mon, 16 Sep 2013 09:53:06 +0000 The cholesterol-lowering efficacy of plant stanol ester (STAEST) added to fat- or milk-based products is well documented. However, their efficacy when added to nondairy liquid drinks is less certain. Therefore, we have investigated the cholesterol-lowering efficacy of STAEST added to a soymilk-based minidrink in the hypercholesterolemic subjects. In a randomized, double-blind, placebo-controlled parallel study, the intervention group () consumed 2.7 g/d of plant stanols as the ester in soymilk-based minidrink (65 mL/d) with the control group () receiving the same drink without added plant stanols once a day with a meal for 4 weeks. Serum total, LDL, and non-HDL cholesterol concentrations were reduced by 8.0, 11.1, and 10.2% compared with controls ( for all). Serum plant sterol concentrations and their ratios to cholesterol declined by 12–25% from baseline in the STAEST group while the ratio of campesterol to cholesterol was increased by 10% in the controls ( for all). Serum precursors of cholesterol remained unchanged in both groups. In conclusion, STAEST-containing soymilk-based low-fat minidrink consumed once a day with a meal lowered LDL and non-HDL cholesterol concentrations without evoking any side effects in subjects consuming normal Western diet. The clinical trial registration number is NCT01716390. Maarit Hallikainen, Johan Olsson, and Helena Gylling Copyright © 2013 Maarit Hallikainen et al. All rights reserved. Quality Assessment of the Genetic Test for Familial Hypercholesterolemia in The Netherlands Mon, 08 Jul 2013 11:51:05 +0000 Introduction. Familial hypercholesterolemia (FH) is an inherited disorder associated with a severely increased risk of cardiovascular disease. Although DNA test results in FH are associated with important medical and ethical consequences, data on accuracy of genetic tests is scarce. Methods. Therefore, we performed a prospective study to assess the overall accuracy of the DNA test used in the genetic cascade screening program for FH in The Netherlands. Individuals aged 18 years and older tested for one of the 5 most prevalent FH mutations, were included consecutively. DNA samples were analyzed by the reference and a counter-expertise laboratory following a standardized procedure. Results. 1003 cases were included. In the end, 317 (32%) carried an FH mutation, whereas in 686 (69%) samples no mutation was found. The overall accuracy of the reference laboratory was 99.8%, with two false positive results identified by the counter-expertise laboratory. Conclusion. The currently used mutation analysis is associated with a very low error rate. Therefore, we do not recommend routine use of duplicate testing. Iris Kindt, Roeland Huijgen, Marieke Boekel, Kristiaan J. van der Gaag, Joep C. Defesche, John J. P. Kastelein, and Peter de Knijff Copyright © 2013 Iris Kindt et al. All rights reserved. HDL, Atherosclerosis, and Emerging Therapies Tue, 28 May 2013 08:38:48 +0000 This review aims to provide an overview on the properties of high-density lipoproteins (HDLs) and their cardioprotective effects. Emergent HDL therapies will be presented in the context of the current understanding of HDL function, metabolism, and protective antiatherosclerotic properties. The epidemiological association between levels of HDL-C or its major apolipoprotein (apoA-I) is strong, graded, and coherent across populations. HDL particles mediate cellular cholesterol efflux, have antioxidant properties, and modulate vascular inflammation and vasomotor function and thrombosis. A link of causality has been cast into doubt with Mendelian randomization data suggesting that genes causing HDL-C deficiency are not associated with increased cardiovascular risk, nor are genes associated with increased HDL-C, with a protective effect. Despite encouraging data from small studies, drugs that increase HDL-C levels have not shown an effect on major cardiovascular end-points in large-scale clinical trials. It is likely that the cholesterol mass within HDL particles is a poor biomarker of therapeutic efficacy. In the present review, we will focus on novel therapeutic avenues and potential biomarkers of HDL function. A better understanding of HDL antiatherogenic functions including reverse cholesterol transport, vascular protective and antioxidation effects will allow novel insight on novel, emergent therapies for cardiovascular prevention. Anouar Hafiane and Jacques Genest Copyright © 2013 Anouar Hafiane and Jacques Genest. All rights reserved. Cholesterol Metabolism and Weight Reduction in Subjects with Mild Obstructive Sleep Apnoea: A Randomised, Controlled Study Thu, 16 May 2013 15:37:37 +0000 To evaluate whether parameters of obstructive sleep apnoea (OSA) associate with cholesterol metabolism before and after weight reduction, 42 middle-aged overweight subjects with mild OSA were randomised to intensive lifestyle intervention () or to control group () with routine lifestyle counselling only. Cholesterol metabolism was evaluated with serum noncholesterol sterol ratios to cholesterol, surrogate markers of cholesterol absorption (cholestanol and plant sterols) and synthesis (cholestenol, desmosterol, and lathosterol) at baseline and after 1-year intervention. At baseline, arterial oxygen saturation () was associated with serum campesterol () and inversely with desmosterol ratios () independently of gender, BMI, and homeostasis model assessment index of insulin resistance (HOMA-IR). Apnoea-hypopnoea index (AHI) was not associated with cholesterol metabolism. Weight reduction significantly increased and serum cholestanol and decreased AHI and serum cholestenol ratios. In the groups combined, the changes in AHI were inversely associated with changes of cholestanol and positively with cholestenol ratios independent of gender and the changes of BMI and HOMA-IR (). In conclusion, mild OSA seemed to be associated with cholesterol metabolism independent of BMI and HOMA-IR. Weight reduction increased the markers of cholesterol absorption and decreased those of cholesterol synthesis in the overweight subjects with mild OSA. Maarit Hallikainen, Henri Tuomilehto, Tarja Martikainen, Esko Vanninen, Juha Seppä, Jouko Kokkarinen, Jukka Randell, and Helena Gylling Copyright © 2013 Maarit Hallikainen et al. All rights reserved.