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Aim: Small dense low-density lipoprotein (sdLDL) has been suggested to be more atherogenic than large buoyant LDL. High-density lipoprotein (HDL) consists of two major subfractions (HDL2, HDL3), and just as controversy remains regarding which of the two is the more powerful negative risk factor for atherosclerosis, associations between sdLDL and these HDL subfractions are unclear.Methods: We measured sdLDL cholesterol (sdLDL-C), HDL2 cholesterol (HDL2-C) and HDL3 cholesterol (HDL3-C) by a newly developed method in 481 Japanese-Americans who were not using lipid-lowering medication, and examined the associations of these cholesterol concentrations with variables related to atherosclerosis.Results: In multivariate analysis, sdLDL-C was positively correlated with the body mass index (BMI), fasting glucose and insulin, 2-h glucose, HOMA-IR, high sensitivity C-reactive protein (hsCRP), and carotid artery intima-media thickness (IMT) after adjustment for age and sex. In particular, sdLDL-C was positively correlated with IMT, even after adjustment for sex, age, smoking status, hypertension, diabetes mellitus and hsCRP. HDL2-C was more closely inversely correlated than total HDL-C with BMI, fasting glucose and insulin, 2-h glucose, HOMA-IR, and hsCRP, whereas HDL3-C was not correlated with these factors. Additionally, HDL2-C was more closely correlated than total HDL-C or HDL3-C with sdLDL-C, LDL-C, triglycerides (TG), and apolipoprotein B (apoB).Conclusions: SdLDL-C was closely associated with insulin resistance and glucose tolerance, lending credence to its potential as a useful risk marker in assessing carotid artery IMT and the present degree of atherosclerosis in Japanese-Americans. The findings also suggest that subjects with higher HDL2-C levels were better protected from atherosclerosis.
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University.
This article was published in the following journal.
Name: Journal of atherosclerosis and thrombosis
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A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established.
Intermediate-density subclass of the high-density lipoproteins, with particle sizes between 7 to 8 nm. As the larger lighter HDL2 lipoprotein, HDL3 lipoprotein is lipid-rich.
A highly dense subclass of the high-density lipoproteins, with particle sizes below 7 nm. They are also known as nascent HDL, composed of a few APOLIPOPROTEIN A-I molecules which are complexed with PHOSPHOLIPIDS. The lipid-poor pre-beta-HDL particles serve as progenitors of HDL3 and then HDL2 after absorption of free cholesterol from cell membranes, cholesterol esterification, and acquisition of apolipoproteins A-II, Cs, and E. Pre-beta-HDL initiate the reverse cholesterol transport process from cells to liver.
A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.
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