J Genest

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..In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol...

..The present article represents the 2009 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult...

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..Novel therapies include injection of purified apolipoprotien AI and short peptides taken orally, mimicking some of the biological effects of apolipoprotein AI...

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..The results of this study have now been incorporated in the new Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease...

..This process may have important implications in preventing and treating atherosclerotic cardiovascular disease...

..This analysis of the the DAIS reveals that the fenofibrate-mediated increase in tHcy levels does not attenuate the beneficial effects of fenofibrate on CAD progression or clinical events...

..However, the extent to which common variation within this gene influences plasma lipid levels and CAD in the general population is unknown...

..These data provide direct evidence that impairment of cholesterol efflux and consequently reverse cholesterol transport is associated with reduced plasma HDL-C levels and increased risk of CAD...

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..Since tHcy is considered an emerging cardiovascular risk factor, the ability of FEN to increase plasma tHcy levels could potentially mitigate the potential of this drug to protect against cardiovascular disease...

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..We conclude that PLC and PLD activities are required for apoA-I-mediated cellular cholesterol efflux, and modulating cellular PA concentration can correct, at least partially, the cholesterol efflux defect in FHD and TD...

..Patients with hyperhomocyst(e)inemia should be treated with at least 400 micrograms of folic acid per day. Alternative treatments are vitamin B6 and B12 supplementation, although optimal doses have yet to be identified...

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..This study emphasizes the significance of sex-associated differences in the biology of homocysteine and underlines the importance of considering these in the determination of threshold values...

..Our results require confirmation in future studies but suggest that a systemic immune response implicating MMP-9 may have an etiologic role in spontaneous preterm birth...

..We sought to evaluate the association between inherited thrombophilia and preeclampsia...

..Mothers who give birth to preterm infants are at increased risk of mortality from coronary heart disease and stroke, but the biological pathways underlying these associations have not been explored...

..The biologic pathways underlying stress-induced preterm birth remain poorly understood...

..However, there has been little attention to carotenoids, tocopherols, and long-chain fatty acids other than n-3 polyunsaturates...

..The finding that nascent particles were depleted of their lipids and remodeled in the presence of plasma lipoproteins raises questions about their stability and subsequent interaction with LCAT...

..Further studies are indicated both in animal models and human populations to better understand the biochemical and physiological pathways to CRH secretion and their aetiological role, if any, in preterm birth...

..They also point to physiologically important, although still only partially understood, metabolic relationships amongst hepatic apoB-100 secretion, cholesterol efflux, and bile acid synthesis...

..Furthermore, the finding supports the possibility that the LRP receptor can act in vivo to mediate clearance of the LCAT-alpha(2)M complex and may significantly influence the bioavailability of LCAT...

..We conclude that apoA-I (E136X) is a cause of HDL-C deficiency in the French Canadian population and is associated with premature CAD...

..New data from fibrate trials can be synthesized with the existing literature to better estimate their effects...

..316, P < 0.02 in FH and r = 0.275, P < 0.009 in non-FH). The detection of circulating PCSK9 in both FH and non-FH subjects means that this assay could be used to monitor response to therapy in a wide range of patients...

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..This process plays in vivo a key role in HDL biogenesis...

..Several studies have examined the association of the methylenetetrahydrofolate reductase (MTHFR) genotype with plasma homocysteine in adults, but few studies have been performed in children...

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..Early onset coronary heart disease (CHD) and calcific aortic valve stenosis are the major complications of this disorder. We now report extensive premature calcification of the aorta in patients with hmzFH...

..These lead to regulation of genes or the modification of proteins involved in vasomotor function, platelet activation, thrombosis and thrombolysis, cell adhesion, apoptosis and cell proliferation, and cellular cholesterol homeostasis...

..This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum...

..Few studies have reported the efficacy of collaborative care involving family physicians and community pharmacists for patients with dyslipidemia...

..Using mouse genetics, the results of the HapMap project and novel genetic approaches will allow the discovery of novel genes in high-density lipoprotein metabolism...

..We therefore investigated the effect of human PCSK5 genetic variants on plasma HDL-C levels...

..Of the cells that compose the atherosclerotic plaque, vascular endothelial cells are the most resistant to cholesterol accumulation. Cholesterol efflux pathways may play an important role in endothelial cholesterol homeostasis...

..The treatment of low HDL-C remains controversial, in part because the only currently available effective medication, niacin, is relatively poorly tolerated and outcomes studies on cardiovascular disease prevention are still pending...

..Increasing the plasma prebeta(1)-LpA-I level by either pharmacological agents or direct infusions might prevent foam cell formation and reduce atherosclerotic vascular disease...

..Thus, S-SMase and LCAT may act in concert and play a crucial role in the biogenesis and maturation of nascent HDL particles...

..These data provide insight into the structure of HDLs and identify potential new roles for SMase in lipoprotein metabolism...

..Unraveling the genetic basis of many lipoprotein disorders has allowed fundamental discoveries in molecular cellular physiology and has paved the way for novel therapeutic approaches...

..Fenofibrate did not change HDL cholesterol levels and caused an increase in LDL cholesterol. Aggressive LDL cholesterol lowering may be the strategy of choice in such patients...

..This gene codes for the cholesterol-efflux regulatory protein (CERP). We investigated the presence of mutations in this gene in patients with familial HDL deficiency...

..Increased lipid transfer to HDL by lipoprotein lipase and reduced HDL clearance by hepatic triglyceride lipase as a result of endurance training are two important mechanisms for increases in HDL observed from exercise...

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..Nevertheless, genomic screening for complex diseases, such as coronary heart disease, and HDL deficiency in particular, may not add additional information to that gained from conventional global cardiovascular risk stratification...

..Hyperhomocysteinemia, in the range of that associated with folate deficiency or with homozygosity for the 677T MTHFR variant, may be associated with disturbed choline metabolism...

..These data suggest that ABCA1 requires a physical association with itself or other molecules for normal function and has important pharmacogenetic implications for individuals with truncation mutations...

..A cross-sectional study of patients treated with statins for at least 8 weeks (CALIPSO) was used as a basis to project the ability of statin monotherapy in getting high CAD-risk patients to an LDL-C level <2.0 mmol/L...

..With the growing epidemic of obesity, dyslipidemias are a component of the metabolic syndrome...

..The aim of this study was to determine whether a novel small molecule RVX-208 affects apolipoprotein (apo)A-I and high-density lipoprotein cholesterol (HDL-C) levels in vitro and in vivo...

..Our data constitute additional evidence for a locus on chromosome 16q23-24 that affects HDL-C levels in two independent French-Canadian studies...

..A porcelain aorta appears to be a feature of HzFH. This has an important impact on surgical planning and management and on possible pathophysiological processes related to the cardiovascular complications of HzFH...

..Altogether, we provide evidence that the carboxyl-terminus of the ASM is crucial for its protein structure, which in turns dictates the enzymatic function and secretion...

..Transfection with a PPARalpha construct upregulated ApoA-I and MTHFR. Our results suggest that hyperhomocysteinemia may increase risk of atherosclerosis by decreasing expression of ApoA-I and increasing expression of CYP7A1...

..Interestingly, in two families studied, mutations in the ABCA1 gene did not segregate with the lipid efflux defect, suggesting that other proteins are involved in the ABCA1-mediated cellular lipid efflux...

..Although statins are widely used to reduce low density lipoprotein cholesterol (LDL-C), there is little information about patient profiles, treatment patterns and goal achievement among statin-treated patients in Canada...

..The impact of conversion from cyclosporine microemulsion (Neoral) to tacrolimus (Prograf) in a large randomized study of stable heart transplant recipients with treated but persistent mild dyslipidemia is reported...

..Thus, our study provides direct evidence for a new link between specific cell lines and the speciation of nascent HDL that occurs by both ABCA1-dependent and -independent pathways...

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..ABCA1 is essential in the initial steps of HDL formation but other plasma events are major modulators of HDL-C levels...

..Taken together, these results demonstrate that: (1) ABCA1 expression varies among tissues, and (2) cholesterol conversion to hydroxycholesterol is an important mechanism for the maintenance of cholesterol homeostasis in fibroblasts...

..No patient with the MS and low HDL-C showed a cellular lipid efflux defect. We conclude that primary cellular lipid efflux defects do not contribute to the low HDL-C frequently encountered in the MS...

..The role of ABC-type transporters, including ABCG1, requires further examination...

..Taken together, these findings provide evidence for a link between the cAMP/PKA-dependent pathway, ABCA1 phosphorylation, and apoA-I mediated cellular cholesterol efflux...

..Understanding the mechanisms governing HDL genesis at the cellular level could provide novel insights into the human atheroprotective system in health and disease...

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..Our results provide a biochemical basis for the HDL biogenesis pathway that involves both ABCA1 and the HCBS, supporting a two binding site model for ABCA1-mediated nascent HDL genesis...

..tacrolimus immunoprophylaxis on these parameters...

..In conclusion, as 20 mg of rosuvastatin can reduce LDL cholesterol by up to 50%, JUPITER will also provide crucial safety data for several thousand patients who should achieve LDL cholesterol levels<50 mg/dl on a long-term basis...

..Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease...

..To evaluate the effect of the calcium channel blocker amlodipine on endothelial function in normotensive patients with coronary disease taking concomitant atorvastatin therapy...

..The JEWEL study program will investigate the use of single-pill amlodipine/atorvastatin as a strategy to improve management of these patients...

..ABCA1 may influence cholesterol efflux in part by enhancing vesicular trafficking from the Golgi to the plasma membrane...

..CONCLUSIONS: The S323I variant may alter C5L2 function and might be one molecular basis contributing to familial combined hyperlipidemia...

..These findings suggest that apoA-I may activate cAMP signaling through G protein-coupled ABCA1 transporter...

..In conclusion, analyses of 9,798 subjects show significant association between HDL-C and a WWOX variant with an allele-specific cis-regulatory function...

..None of the genes residing in the significantly restricted 2.37-Mb region has been associated previously with HDL-C metabolism. CONCLUSIONS: This study provides significant evidence for a gene influencing HDL-C on chromosome 4q31.21...

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..0) and recommendations regarding additional investigations of potential use in the further evaluation of coronary artery disease risk in subjects in the moderate-risk category...

..However, normalization was attained when patients were supplemented with folic acid. Further controlled studies are required to evaluate the determinants and treatment of elevated plasma homocysteine in pediatric transplant patients...