Lipoprotein distribution of apolipoprotein C-III and its relationship to the presence in plasma of triglyceride-rich remnant lipoproteins

Abstract

The distribution of apolipoprotein C-III (apoC-III) between high-density lipoprotein (HDL) and apoB-containing lipoproteins has been used in lipid-lowering angiographic trials to establish a link between impaired triglyceride (TG)-rich lipoprotein (TRL) metabolism and the progression of coronary artery disease. To investigate the extent to which plasma lipoprotein apoC-III levels reflect the presence in plasma of potentially atherogenic remnant lipoproteins, we studied 4 groups of subjects: (1) normolipidemic (NL, n = 10), (2) hypercholesterolemic (HC, type IIa, low-density lipoprotein cholesterol [LDL-C] > 3.4 mmol/L, n = 10), (3) hypertriglyceridemic (HTG, type IV, TG > 2.3 mmol/L, n = 10), and (4) combined hyperlipidemic (CHL, type IIb, TG > 2.3 mmol/L, LDL-C > 3.4 mmol/L, n = 10). The apoC-III level was measured in plasma lipoproteins separated either by density (ultracentrifugation) or by size (fast protein liquid chromatography [FPLC]), and was compared with 4 parameters reflecting remnant lipoprotein levels (ie, very-low-density lipoprotein cholesterol [VLDL-C], intermediate-density lipoprotein cholesterol [IDL-C], remnant-like particle cholesterol [RLP-C], and intermediate-sized lipoprotein [ISL] apoE). Our results demonstrate that (1) increased amounts of apoC-III associated with plasma VLDL, TRL, or apoB-containing lipoproteins (LpB), as well as increased levels of TRL remnant lipoproteins, are a characteristic of HTG patients rather than patients with increased LDL, and (2) plasma levels of apoC-III in VLDL, TRL, or LpB, as well as the HDL apoC-III to LpB apoC-III ratios, are strongly correlated with circulating levels of TRL, although these apoC-II parameters more closely reflect the balance between TRL TG production and lipolysis than the extent of plasma TRL remnant accumulation.