Remnants of lipoproteins of intestinal and hepatic origin in familial dysbetalipoproteinemia.

Abstract

We used the low molecular weight form of apolipoprotein B (B-48) as a marker for the identification of remnant particles formed from chyiomicrons in the plasma of patients with familial dysbetalipoproteinemia. In the serum of patients fasted 14 hours, the d < 1.006 g/cm 3 lipoproteins of prebeta mobility, separated by starch block electrophoresis, contained only the primary hepatogenous species of apolipoprotein B (B-100), and their llpld composition resembled that of normal prebeta very low density lipoproteins. In contrast, the fraction with beta mobility contained both the B-48 and B-100 proteins; the B-48 protein was found primarily among the largest particles. All fractions of beta mobility were greatly enriched with choiesteryi esters. The beta fraction thus contains remnant particles which appear to originate both from chyiomicrons and hepatogenous very low density lipoproteins. It appears that these remnant particles share a common removal mechanism which is impaired in familial dysbetalipoproteinemia. (Arteriosclerosis 3:47-56, January/February 1983) amilial dysbetalipoproteinemia (F. dys.) (type III hyperlipoproteinemia) is now recognized as a disorder in which remnant-like particles, formed from triglyceride-rich lipoproteins, accumulate in plasma.12 Clinically, it is associated with arteriosclerosis of both the coronary and peripheral circulations. 3These remnant-like lipoprotein particles are enriched with choiesteryi esters 1 2 ' 4 and have beta mobility upon electrophoresis in agarose gel, in contrast with normal very low density lipoproteins (VLDL), which have prebeta mobility. The electrophoretic mobility of remnant particles is accounted for principally by deficiency of the C-apoproteins, which are normally the preponderant species in VLDL, with retention of appreciable quantities of less anionic apolipoprotein E (apo E). 5 The initial stages of intravascular lipolysis appear to proceed relatively normally. Removal of remnant particles from the plasma normally occurs rapidly by means of receptor-mediated endocytosis in the liver.2 In F. dys., however, there is

Low Expression of the Apolipoprotein B mRNA–Editing Transgene in Mice Reduces LDL Levels but Does Not Cause Liver Dysplasia or Tumors

“…Type III hypercholesterolemia is characterized clinically by the elevation of plasma cholesterol and triglyceride levels, the accumulation of cholesterol-rich ␤-VLDL particles (apoB-48 -containing ␤-VLDL and apoB-100 -containing VLDL remnants) in the plasma, and the formation of lipid deposits in the skin and artery wall. 6,29 In vitro experiments using mouse peritoneal macrophages have shown that the chylomicron remnants are effective in causing cholesteryl ester accumulation in these cells. 30 Recently, transgenic apoB-100 -and apoB-48 -only mice on the apoE-null background were used to study the atherogenicity of apoB proteins.…”

Postprandial Hyperlipidemia and Atherosclerosis

“…1). An increase of remnant lipoproteins is a risk factor for atherosclerosis (2). The remnant lipoprotein is as well as the oxidized low density lipoprotein (LDL), easily taken into the macrophage in the arterial wall, promoting foam cell formation of macrophages and forming the atherosclerotic lesion (Fig.…”

Role of apolipoprotein E in the lipolytic conversion of beta-very low density lipoproteins to low density lipoproteins in type III hyperlipoproteinemia.

“…The f3-VLDL include two distinct subclasses of lipoproteins (4,5), which can be isolated by agarose chromatography; they are referred to as fraction I and fraction II. Fraction I consists of large particles (700-800 A in diameter) containing apolipoprotein E (apo-E) and a low molecular weight form of apo-B referred to as B48.…”