Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment.

Abstract

A s bstract. The effects of triglyceridemia on plasma lipoproteins were investigated in 16 hypertriglyceridemic (HTG) subjects (222-2,500 mg/dl) before and after the initiation ofbezafibrate therapy. Bezafibrate caused a mean reduction of 56% in plasma triglyceride and increased the levels of lipoprotein and hepatic triglyceride lipases by 260 and 213%, respectively. The natures of very low density lipoprotein (VLDL), isolated at plasma density and of low and high density lipoprotein (LDL and HDL), separated by zonal ultracentrifugation, were determined. HTG-LDL appears as multiple fractions whereas HTG-HDL is seen predominantly as HDL3.HTG-VLDL is relatively poor in apoproteins and triglycerides but enriched in free and esterified cholesterol. HTG-LDL (main fraction) is depleted offree and esterified cholesterol but enriched in apoprotein and triglyceride. It is also denser and smaller than normal. HTG-HDL3 is denser than N-HDL3 and demonstrates compositional abnormalities similar to those of HTG-LDL. With the reduction of the VLDL mass, all abnormalities revert towards normal. This is accompanied by an increase in LDL-apoprotein B and cholesterol levels, which indicates an increased conversion of VLDL to LDL.Significant correlations between plasma triglyceride and the degree of all abnormalities are shown. The data obtained during treatment corroborate these relationships.The observations support the concept that most abnormalities reflect the degree of triglyceridemia.Address reprint requests to Dr. Eisenberg, Lipid Research Laboratory, Department of Medicine B, Hadassah University Hospital.Received for publication 12 December 1983 and in revised form 4 April 1984.We suggest that plasma core-lipid transfer protein(s) is an effector ofthe abnormal cholesteryl ester distribution. Its prolonged action on increasingly large and slowly metabolized VLDL populations would entail a correspondingly excessive transfer of cholesteryl ester to VLDL and of triglyceride to LDL and HDL. It is calculated that, in moderate HTG, LDL and HDL contain only 50% of the normal cholesterol load. It is suggested that cholesteryl ester redistribution in HTG might be important in regulating metabolic events.

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

“…Numerous studies have demonstrated their association with extensive, pro-atherogenic changes of LDL and HDL. 13,35,36 In addition there is evidence that large VLDL can themselves promote cholesterol accumulation by cells. 37 Modulation of the LDL pro®le, notably the presence of small, dense LDL particles, has attracted widespread attention because of the links with coronary heart disease.…”

Plasma triglyceride and coronary heart disease.

“…Variations in LDL particle size and density have been characterized using a variety of techniques 97 -99 and have been associated with differences in plasma triglyceride levels. 100 - 101 Distinct subclasses of LDL particles have been identified by density gradient ultracentrifugation 97 and by gradient gel electrophoresis; the latter technique separates LDL particles by size and charge, 102 and has allowed the identification of two LDL subclass patterns, denoted patterns A and B. 103 Pattern A is characterized by a predominance of relatively large, buoyant, LDL subclasses in individual subjects, while pattern B is characterized by a predominance of small, dense, LDL particles.…”

HDL Apolipoprotein A-I and HDL Apolipoprotein A-II Concentrations in Male Company Employees in Westphalia Aged 40 Years and Older

“…Furthermore, it has been shown that a less dense HDL2 subfraction (relative high lipid/apolipoprotein ratio) is epidemiologically associated with reduced coronary heart disease, while a more dense HDL 3 subfraction (relatively low lipid/ apolipoprotein ratio) is thought to be unrelated to such disease (22,23). Nevertheless, recent studies have shown that HDL in individuals with hypertriacylglycerolaemia mainly consist of HDL 3 , which are enriched with apolipoproteins and triglycerides and which are depleted of cholesterol (24). Furthermore, it has been reported that alcohol consumption, which is known to be associated with high HDL cholesterol (25 -27) and frequently with hypertriacylglycerolaemia (28, 29), mainly resulted in an enhanced level of HDL 3 mass without affecting HDL 2 mass (30).…”