Vascular Medicine Apolipoprotein C-III and the Metabolic Basis for Hypertriglyceridemia and the Dense Low-Density Lipoprotein Phenotype
نویسندگان
چکیده
Background—Here, we aim to identify defects of apolipoprotein (apo) B lipoprotein metabolism that characterize hypertriglyceridemia, focusing on apoC-III and apoE. Methods and Results—We studied the transport of plasma apoB within 21 distinct subfractions as separated by anti–apoC-III and anti–apoE immunoaffinity chromatography and ultracentrifugation in 9 patients with moderate hypertriglyceridemia and 12 normotriglyceridemic control subjects. Hypertriglyceridemia was characterized by a 3-fold higher liver secretion of very low-density lipoprotein (VLDL) that had apoC-III but not apoE and a 50% lower secretion of VLDL with both apoC-III and apoE (both P 0.05). This shift in VLDL secretion pattern from apoE to apoC-III resulted in significantly reduced clearance of light VLDL ( 39%; P 0.05), compatible with the antagonizing effects of apoC-III on apoE-induced clearance of triglyceride-rich lipoproteins. In addition, rate constants for clearance were reduced for apoE-containing triglyceride-rich lipoproteins in hypertriglyceridemia, associated with increased apoC-III contents of these particles. LDL distribution shifted from light and medium LDL to dense LDL in hypertriglyceridemia through a quartet of kinetic perturbations: increased flux from apoC-III–containing triglyceride-rich lipoproteins, a shift in liver LDL secretion pattern from light to dense LDL, an increased conversion rate from light and medium LDL to dense LDL, and retarded catabolism of dense LDL. Conclusions—These results support a central role for apoC-III in metabolic defects leading to hypertriglyceridemia. Triglyceride-rich lipoprotein metabolism shifts from an apoE-dominated system in normotriglyceridemic participants characterized by rapid clearance from circulation of VLDL to an apoC-III–dominated system in hypertriglyceridemic patients characterized by reduced clearance of triglyceride-rich lipoproteins and the formation of the dense LDL phenotype. (Circulation. 2010;121:1722-1734.)
منابع مشابه
Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype.
BACKGROUND Here, we aim to identify defects of apolipoprotein (apo) B lipoprotein metabolism that characterize hypertriglyceridemia, focusing on apoC-III and apoE. METHODS AND RESULTS We studied the transport of plasma apoB within 21 distinct subfractions as separated by anti-apoC-III and anti-apoE immunoaffinity chromatography and ultracentrifugation in 9 patients with moderate hypertriglyce...
متن کاملThe association between small dense low density lipoprotein,apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio and coronary artery stenosis
Abstract Background: Recently, small dense low density lipoprotein (sdLDL) has been highlighted as a new risk factor for the coronary artery disease (CAD).Small dense LDLs are believed to be atherogenic since these particles are taken up more easily by arterial wall. They are readily oxidized and have reduced affinity for low density lipoprotein (LDL) receptor and increased affinity...
متن کاملبررسی قطر LDL-c و سطح sdLDL-c سرم در ارتباط با فنوتیپ هیپرتریگلیسریدمی با دور کمر بالا در جمعیتی از زنان
Background and Objectives: Obesity is a major risk factor of cardiovascular diseases. Visceral adipose tissue (VAT) plays an important role in complications obesity. Although the measurement of waist circumference is a useful index for evaluating obesity and its complications, always increasing of waist circumference is not associated with VAT accumulation. HTGW (Hypertriglyceridemic waist circ...
متن کاملThe crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia.
PURPOSE OF REVIEW To describe the roles of apolipoprotein C-III (apoC-III) and apoE in VLDL and LDL metabolism RECENT FINDINGS ApoC-III can block clearance from the circulation of apolipoprotein B (apoB) lipoproteins, whereas apoE mediates their clearance. Normolipidemia is sustained by hepatic secretion of VLDL and IDL subspecies that contain both apoE and apoC-III (VLDL E+C-III+). Most of t...
متن کاملRole of apolipoproteins E and C in type V hyperlipoproteinemia.
Type V hyperlipoproteinemia is characterized by elevations of chylomicron (CM) and very low density lipoprotein (VLDL) triglycerides. The development of this lipid disorder involves a multitude of metabolic derangements including deficient clearance of triglycerides and/or their increased output aggravated by obesity, diabetes, alcohol intake, or use of some hormones. Some studies have suggeste...
متن کامل