Heterogeneity of apolipoprotein A-I turnover in subjects with reduced concentrations of plasma high density lipoprotein cholesterol

Abstract

Reduced plasma levels of high density lipoprotein cholesterol (HDLC) and apolipoprotein A-I (apoA-I) are both indicators of increased risk of developing coronary artery disease. We have used autologous 125-I-HDL to determine the rates of production (PR) and fractional catabolism (FCR) of apoA-I, the major, structural apolipoprotein in HDL, in three groups of men that included the following: four normal subjects (triglyceride [TG] = 61.0 ± 5.0 mg/dL, HDLC = 51.5 ± 7.0 mg/dL), four subjects with both hypertriglyceridemia and reduced HDLC (TG = 360.3 ± 111.1 mg/dL, HDLC = 23.8 ± 6.1 mg/dL), and seven subjects with only reduced HDLC (TG = 103.7 ± 49.5 mg/dL, HDLC = 25.6 ± 6.1 mg/dL). In the group with both the high TG and low HDL, apoA-I PR was significantly greater than the apoA-I PR in the normal group (14.2 ± 2.3 v 10.6 ± 1.9 mg/kg · d, P < .05). ApoA-I FCR was also significantly greater in the former group v normals (0.38 ± 0.08 v 0.21 ± 0.04 d −1, P < .02). In contrast, the group of subjects with only low HDLC had a significantly lower apoA-I PR v the normal subjects (7.1 ± 2.0 v 10.6 ± 1.9 mg/kg · d; P < .05). ApoA-I FCR was variable in the group with isolated low HDLC, but the mean FCR was not different from normal (0.26 ± 0.09 v 0.21 ± 0.04 d −1). These results indicate significant differences in the rates of production of apoA-I between subjects with the combination of low HDLC and high TG levels and subjects with only low HDLC levels. The underlying metabolic defects present in each group remain to be determined.