Plasma triglyceride determines structure-composition in low and high density lipoproteins.

Abstract

Because the association of hypertriglyceridemia and premature atherosclerosis is not due to the direct effects of the triglyceride molecule itself, we studied the effects of increased plasma triglyceride-rich lipoproteins on the composition and structure of low density lipoprotein (LDL) and high density lipoprotein (HDL). We found profound changes in the core and surface domains of both lipoproteins with increasing triglyceridemia. Core cholesterol esters were progressively depleted and replaced by triglyceride molecules. Highly significant negative correlations were found between cholesterol ester/protein ratios (r = cause of accelerated coronary artery disease in familial hypercholesterolemia. 5 The increased risk for coronary artery disease observed in hypertriglyceridemia, however, is poorly understood and probably does not reflect the direct effects of the triglyceride molecule itself. Recently, Hulley and associates 6 have suggested that the low HDL cholesterol levels found in hypertriglyceridemic patients contribute significantly to this phenomen. Such patients also have low LDL cholesterol levels and high VLDL cholesterol and triglyceride levels. The metabolic pathways responsible for these observations have not been previously elucidated.-In this paper we suggest that these abnormalities may merely reflect the state of hypertriglyceridemia. Specifically, we propose that the replacement of cholesterol ester in HDL and LDL by triglycerides contributes to the low levels of cholesterol in these lipoproteins. In recent in vitro experiments, 7 " 9 we showed that cholesterol ester-triglyceride bidirectional transfer processes, originally observed by Nichols and Smith, 10 play a major role in determining the structure and composition of LDL and HDL. We

Associations of lipoprotein cholesterols, apolipoproteins A-I and B, and triglycerides with carotid atherosclerosis and coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) Study.

“…1113 The fibrinolytic defect may be mediated by triglyceride-induced plasminogen activator inhibitor-1 elevation. 14 Our hypothesis suggests that CHD may be related to greater apoB than LDL-C elevations because higher triglyceride levels, which favor thrombosis, also alter LDL composition, 51 lowering its ratio of cholesterol to apoB, 15 and raise total plasma apoB because of the apoB in very-low-density lipoprotein. The hypothesis that triglyceride elevation contributes more to CHD than carotid disease, together with its known effect of lowering plasma HDL-C levels, would also explain why we and others 52 found less HDL reduction with early carotid atherosclerosis than is usually reported with CHD.…”

“…10 A tendency to thrombosis may be favored by abnormalities in triglyceride metabolism. 1114 Since impaired metabolism of triglyceride-rich lipoproteins also lowers HDL levels and affects LDL structure, lowering its ratio of cholesterol to apolipoprotein, 15 we reasoned that subtle lipid profile differences may exist between persons with early atherosclerosis and those with later stenotic disease.…”

Lipoprotein distribution and composition in obesity: their association with central adiposity

“…Triglycerides have the strongest impact on the lipoprotein pro®le. 13,14 To our knowledge, only two studies, focusing on the LDL pro®le, have adjusted for triglycerides; in one 15 the presence of small, dense LDL was independently related to visceral fat accumulation, whilst the association was no longer signi®cant when corrected for triglycerides in a more recent study. 16 It thus remains unclear whether central obesity could in¯u-ence lipoprotein metabolism directly or via the agency of raised triglyceride levels.…”

Lipoprotein changes in children after liver transplantation: Mild hypertriglyceridemia and a decrease in HDL/HDL ratio

“…[29][30][31] Although the composition of HDL 2 and HDL 3 particles did not differ in children with transplants and the control group, the ratio of these two major HDL subfractions differed significantly. In the control group; levels of HDL 3 were more than twice those of HDL 2 (HDL 3 protein/HDL 2 protein 2.3), whereas in the post-liver transplantation group HDL 2 levels were increased compared with HDL 3 (HDL 3 protein/HDL 2 protein 1.27; Fig.…”