Cholesterol The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . 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. Leishmania major Self-Limited Infection Increases Blood Cholesterol and Promotes Atherosclerosis Development Sun, 28 Apr 2013 08:35:29 +0000 Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages. Luciana R. Fernandes, Ana Cecília C. Ribeiro, Marcela Segatto, Luís Felipe F. F. Santos, Joana Amaral, Luciane R. Portugal, and Jacqueline I. A. Leite Copyright © 2013 Luciana R. Fernandes et al. All rights reserved. Discordance of Non-HDL and Directly Measured LDL Cholesterol: Which Lipid Measure is Preferred When Calculated LDL Is Inaccurate? Tue, 23 Apr 2013 15:19:57 +0000 Objective. To determine if non-HDL cholesterol (N-HDL) and directly measured LDL cholesterol (D-LDL) are clinically equivalent measurements. Patients and Methods. Eighty-one subjects recruited for 2 cholesterol treatment studies had at least 1 complete fasting lipid panel and D-LDL performed simultaneously; 64 had a second assessment after 4 to 6 weeks, resulting in 145 triads of C-LDL, D-LDL, and N-HDL. To directly compare N-HDL to D-LDL and C-LDL, we normalized the N-HDL by subtracting 30 from the N-HDL (N-HDLA). Results. There was significant correlation between N-HDLA, D-LDL, and C-LDL. Correlation was significantly greater between N-HDLA and C-LDL than between N-HDLA and D-LDL. A greater than 20 mg/dL difference between measures was observed more commonly between N-HDLA and D-LDL, 29%, than between C-LDL and N-HDLA, 11% (), and C-LDL and D-LDL, 17% (). Clinical discordance was most common, and concordance was least common between N-HDL and D-LDL. Conclusions. Our findings suggest that N-HDL cholesterol and D-LDL cholesterol are not clinically equivalent and frequently discordant. As N-HDL may be superior to even C-LDL for predicting events in statin-treated patients, utilizing N-HDL to guide therapy would appear to be preferable to D-LDL when C-LDL is inaccurate. Lawrence Baruch, Valerie J. Chiong, Sanjay Agarwal, and Bhanu Gupta Copyright © 2013 Lawrence Baruch et al. All rights reserved. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease Sun, 14 Apr 2013 09:28:39 +0000 Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia) are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs) may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk. Agostino Di Ciaula, David Q.-H. Wang, Leonilde Bonfrate, and Piero Portincasa Copyright © 2013 Agostino Di Ciaula et al. All rights reserved. Predictors of Metabolic Syndrome in the Iranian Population: Waist Circumference, Body Mass Index, or Waist to Hip Ratio? Sun, 24 Mar 2013 13:20:25 +0000 This study aimed to investigate whether body mass index (BMI), waist circumference (WC), or waist to hip ratio (WHR) could be a better predictor of metabolic syndrome and, if so, what would be the cutoff points for these surrogates to appropriately differentiate metabolic syndrome in different age and sex subgroups. Methods. The present cross-sectional study was conducted on a sample of Isfahan Cohort Study (ICS). In total, 468 individuals (194 with and 274 subjects without metabolic syndrome) according to the National Cholesterol Education Program’s Adult Treatment Panel III (ATP-III) criteria were selected. Anthropometric indices were measured and plotted using receiver-operating characteristic (ROC) curves. Results. According to ROC curve analysis, WC and WHR parameters were better indicators of metabolic syndrome compared to BMI in women, whereas in men WHR had a lower discriminating value compared to the other two parameters. Among these three anthropometric parameters, BMI had a lower sensitivity and WC and WHR both had a higher sensitivity for predicting metabolic syndrome in women compared with in men. The cut points for WC were nearly equal in men and women, 90.3 versus 90.0, respectively. Women had higher cut points for BMI (28.5 kg/m2) compared to men (26.0 kg/m2). Our results showed the highest sensitivity and specificity for WC cut points specially in women. To predict metabolic syndrome, we looked into optimal age-specific cut points for BMI, WC, and WHR. The results indicated that WC had the highest discriminating value compared to other indicators in the different age subgroups. The optimal cut points for all three parameters gradually increased with age. Conclusion. Our results demonstrated that regardless of gender and age variables, WC could be a preferred parameter for predicting metabolic syndrome compared to BMI and WHR in Iranian population. Mojgan Gharipour, Nizal Sarrafzadegan, Masoumeh Sadeghi, Elham Andalib, Mohammad Talaie, Davood Shafie, and Esmaiel Aghababaie Copyright © 2013 Mojgan Gharipour et al. All rights reserved. HDL-C Response Variability to Niacin ER in US Adults Tue, 26 Feb 2013 09:35:58 +0000 Background. Niacin is the most effective treatment currently available for raising HDL-C levels. Objective. To evaluate if gender and baseline lipid levels have an effect on the HDL-C response of niacin ER and to identify factors that predict response to niacin ER at the 500 mg dose. Material and Methods. The change in HDL-C effect between baseline and follow-up levels was quantified in absolute change as well as dichotomized into high versus low response (high response was defined as an HDL-C effect of >15% increase and low response was HDL-C <5%) in a sample of 834 individuals. Results. Both males and females with low HDL-C levels at baseline exhibited a response to treatment in the multivariate model (males, HDL-C <40 mg/dL: , 95% CI: 2.36–11.39; females, HDL-C <50 mg/dL: , 95% CI: 1.84–15.79). There was also a significant difference in the mean HDL-C effect between baseline and follow-up HDL-C levels in the 500 mg niacin ER dose group for both males (mean HDL-C effect = 0.08, ) and females (mean HDL-C effect = 0.10, ). Conclusion. Baseline HDL-C levels are the biggest predictor of response to niacin ER treatment for both males and females among the factors evaluated. Jennifer B. Christian, Eric J. Olson, Jeffery K. Allen, and Kimberly A. Lowe Copyright © 2013 Jennifer B. Christian et al. All rights reserved. Pediatric Metabolic Syndrome: From Prevention to Treatment Sun, 11 Nov 2012 17:08:56 +0000 Roya Kelishadi, Parinaz Poursafa, Sarah D. de Ferranti, Peter Schwandt, Khosrow Adeli, Altan Onat, and Samuel S. Gidding Copyright © 2012 Roya Kelishadi et al. All rights reserved. Effects of Diet, Aerobic Exercise, or Both on Non-HDL-C in Adults: A Meta-Analysis of Randomized Controlled Trials Thu, 08 Nov 2012 09:02:12 +0000 Purpose. To use the meta-analytic approach to examine the effects of diet (D), aerobic exercise (E), or both (DE) on non-high-density lipoprotein cholesterol (non-HDL-C) in adults. Methods. Randomized controlled trials in adults ≥18 years of age were included. A mixed-effect model was used to combine effect size (ES) results within each subgroup and to compare subgroups (). Heterogeneity was examined using the and statistics, and 95% confidence intervals (CI) were also calculated. Statistical significance was set at , while a trend for statistical significance was set between , and ≤0.10. Results. A statistically significant exercise minus control group decrease in non-HDL-C was found for DE (7 ESs, 389 participants,  mg/dL, 95% to −0.6, , , , %), a trend for the D group (7 ESs, 402 participants,  mg/dL, 95% to 1.6, , , , %), and no change for the E group (7 ESs, 387 participants,  mg/dL, 95% to 13.1, , , , %). Overall, no statistically significant between-group differences were found (, ). Conclusions. Diet combined with aerobic exercise may reduce non-HDL-C among adults in some settings. George A. Kelley and Kristi S. Kelley Copyright © 2012 George A. Kelley and Kristi S. Kelley. All rights reserved. Cholesterol: Its Regulation and Role in Central Nervous System Disorders Wed, 17 Oct 2012 11:12:28 +0000 Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions. Matthias Orth and Stefano Bellosta Copyright © 2012 Matthias Orth and Stefano Bellosta. All rights reserved. Relationship of Lifestyle Medical Advice and Non-HDL Cholesterol Control of a Nationally Representative US Sample with Hypercholesterolemia by Race/Ethnicity Mon, 15 Oct 2012 15:11:06 +0000 Objective. The main purpose of this study was to evaluate the associations of lifestyle medical advice and non-HDL cholesterol control of a nationally representative US sample of adults with hypercholesterolemia by race/ethnicity. Methods. Data were collected by appending sociodemographic, anthropometric, and laboratory data from two cycles of the National Health and Nutrition Survey (2007-2008 and 2009-2010). This study acquired data from male and female adults aged ≥ 20 years (N = 11,577), classified as either Mexican American (MA), (), other Hispanic (OH) (), Black non-Hispanic (BNH) (), or White non-Hispanic (WNH) (). Results. Minorities were more likely to report having received dietary, weight management, and exercise recommendations by healthcare professionals than WNH, adjusting for confounders. Approximately 80% of those receiving medical advice followed the recommendation, regardless of race/ethnicity. Of those who received medical advice, reporting “currently controlling or losing weight” was associated with lower non-HDL cholesterol. BNH who reported “currently controlling or losing weight” had higher non-HDL cholesterol than WNH who reported following the advice. Conclusion. The results suggest that current methods of communicating lifestyle advice may not be adequate across race/ethnicity and that a change in perspective and delivery of medical recommendations for persons with hypercholesterolemia is needed. Joan Anne Vaccaro and Fatma G. Huffman Copyright © 2012 Joan Anne Vaccaro and Fatma G. Huffman. All rights reserved. Improving Total-Cholesterol/HDL-Cholesterol Ratio Results in an Endothelial Dysfunction Recovery in Peripheral Artery Disease Patients Tue, 25 Sep 2012 14:29:23 +0000 Aims. To evaluate the effects of variations of total-cholesterol/HDL-cholesterol ratio and the effects of the atorvastatin on endothelial function in peripheral artery disease (PAD). Material and Methods. A prospective, randomised controlled study was carried out in 150 PAD patients. Patients randomized to the control group () were treated with antiplatelet drugs, angiotensin-converting-enzyme inhibitors and cardiovascular-risk-factor control. Experimental group () also received treatment with atorvastatin for a month. It was determined baseline nitrite plasma levels and total-cholesterol/HDL-cholesterol ratio and after one month of treatment in both groups. It was also analysed the correlation between the gradient of nitrite levels and the differential of total-cholesterol/HDL ratio in treatment group. Results. After a month, a reduction in nitrite levels was detected in treatment group ( μM versus 5.7 ± 1.8 μM, ). It was shown a higher decrease in nitrite plasma levels in the atorvastatin group finding lower levels assessments (5.7 ± 1.8 μM versus 13.1 ± 9.1 μM, resp., ). A significant reduction in total-cholesterol/HDL-cholesterol ratio was observed in statin group after treatment (). A strong correlation was found between the gradient of nitrite levels and the differential of total-cholesterol/HDL-cholesterol ratio in atorvastatin group (; ). Conclusions. Improvement of nitrite levels are associated with decreased total cholesterol/HDL ratio values in PAD patients treated with atorvastatin. Silvia Bleda, Joaquín de Haro, César Varela, Leticia Esparza, Javier Rodriguez, and Francisco Acin Copyright © 2012 Silvia Bleda et al. All rights reserved. Lipoprotein(a): Cellular Effects and Molecular Mechanisms Thu, 06 Sep 2012 15:24:44 +0000 Lipoprotein(a) (Lp(a)) is an independent risk factor for the development of cardiovascular disease (CVD). Indeed, individuals with plasma concentrations >20 mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the population. Circulating levels of Lp(a) are remarkably resistant to common lipid lowering therapies, and there are currently no robust treatments available for reduction of Lp(a) apart from plasma apheresis, which is costly and labour intensive. The Lp(a) molecule is composed of two parts, an LDL/apoB-100 core and a unique glycoprotein, apolipoprotein(a) (apo(a)), both of which can interact with components of the coagulation cascade, inflammatory pathways, and cells of the blood vessel wall (smooth muscle cells (SMC) and endothelial cells (EC)). Therefore, it is of key importance to determine the molecular pathways by which Lp(a) exerts its influence on the vascular system in order to design therapeutics to target its cellular effects. This paper will summarise the role of Lp(a) in modulating cell behaviour in all aspects of the vascular system including platelets, monocytes, SMC, and EC. Kirsten Riches and Karen E. Porter Copyright © 2012 Kirsten Riches and Karen E. Porter. All rights reserved. The Effects of Unripe Grape Juice on Lipid Profile Improvement Wed, 29 Aug 2012 13:21:03 +0000 Introduction. Consumption of unripe grape juice (verjuice) has been portrayed by the traditional belief, as a means of combating dyslipidemia. We aimed to evaluate the effects of unripe grape juice consumption on lipid profile in healthy human volunteers. Methods. We asked 42 enrolled volunteers to drink 10 cc of verjuice within 30 minutes to 2 hours after lunch and 10 cc of it after dinner. After taking 120 doses of verjuice, another fasting lipid profile was obtained from each participant. The statistical analysis was performed by SPSS 13 software. Results. After analysis of the data, the mean ± standard deviation for all the variables was obtained. Among those improvement of HDL-C was significant after the trial (𝑃value<0.001). TG, TC, and LDL improvement were not significant. Conclusion. Our study declared that verjuice has a dramatic effect on improving HDL-C level of serum but no any other lipid improvement effect was obtained. Mohammad Javad ZibaeeNezhad, Esmael Mohammadi, Mohammad Ali Babaie Beigi, Fatemeh Mirzamohammadi, and Oveis Salehi Copyright © 2012 Mohammad Javad ZibaeeNezhad et al. All rights reserved. Immune Response to Lipoproteins in Atherosclerosis Thu, 23 Aug 2012 10:25:43 +0000 Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis. Sonia Samson, Lakshmi Mundkur, and Vijay V. Kakkar Copyright © 2012 Sonia Samson et al. All rights reserved. MicroRNA Regulation of Cholesterol Metabolism Sun, 05 Aug 2012 09:39:25 +0000 Disruption of cellular cholesterol balance results in pathologic processes including atherosclerosis, metabolic syndrome, type II diabetes and Alzheimer’s disease. Maintenance of cholesterol homeostasis requires constant metabolic adjustment, achieved partly through the fine regulation of the classical transcription factors (e.g., by SREBP and LXR), but also through members of a class of noncoding RNAs termed miRNAs. Some miRNAs have now been identified to be potent post-transcriptional regulators of lipid metabolism genes, including miR-122, miR-33, miR-758, and miR-106b. Different strategies have been developed to modulate miRNA effects for therapeutic purposes. The promise demonstrated by the use of anti-miRs in human preclinical studies, in the case of miR-122, raises the possibility that miR-33, miR-758, and miR-106b may become viable therapeutic targets in future. This review summarizes the evidence for a critical role of some miRNAs in regulating cholesterol metabolism and suggests novel ways to manage dyslipidemias and cardiovascular diseases. Noemi Rotllan and Carlos Fernández-Hernando Copyright © 2012 Noemi Rotllan and Carlos Fernández-Hernando. All rights reserved.