Apolipoprotein C3 (APOC3) mutations carriers typically display high plasma high-density lipoprotein cholesterol (HDL-C) and low triglycerides (TGs). We set out to investigate the prevalence and clinic Show more
Apolipoprotein C3 (APOC3) mutations carriers typically display high plasma high-density lipoprotein cholesterol (HDL-C) and low triglycerides (TGs). We set out to investigate the prevalence and clinical consequences of APOC3 mutations in individuals with hyperalphalipoproteinemia. Two novel mutations (c.-13-2A>G and c.55+1G>A) and one known mutation (c.127G>A;p.Ala43Thr) were found. Lipid profiles and apoCIII isoform distributions were measured. c.55+1G>A mutation carriers displayed higher HDL-C percentiles (35.6 ± 35.8 vs 99.0 ± 0, p = 0.002) and lower TGs (0.51 (0.37-0.61) vs 1.42 (1.12-1.81) mmol/l, p = 0.007) and apoCIII levels (4.24 ± 1.57 vs 7.33 ± 3.61 mg/dl, p = 0.18). c.-13-2A>G mutation carriers did not display significantly different HDL-C levels (84.0 ± 30.0 vs 63.7 ± 45.7, p = 0.50), a trend towards lower TGs [0.71 (0.54 to 0.78) vs 0.85 (0.85 to -) mmol/l, p = 0.06] and significantly lower apoCIII levels (3.09 ± 1.08 vs 11.45 ± 1.06 mg/dl, p = 0.003). p.Ala43Thr mutation carriers displayed a trend towards higher HDL-C percentiles (91.2 ± 31.8 vs 41.0 ± 29.7 mmol/l, p = 0.06) and significantly lower TGs [0.58 (0.36-0.63) vs 0.95 (0.71-1.20) mmol/l, p = 0.02] and apoCIII levels (4.92 ± 2.33 vs 6.60 ± 1.60, p = 0.25). Heterozygosity for APOC3 mutations results in high HDL-C and low TGs and apoCIII levels. This favourable lipid profile in patients with genetically low apoCIII levels holds promise for current studies investigating the potential of apoCIII inhibition as a novel therapeutic in cardiovascular disease prevention. Show less
The ABC transporter ABCA1 plays a key role in the first steps of the reverse cholesterol transport pathway by mediating lipid efflux from macrophages. Previously, it was demonstrated that human ABCA1 Show more
The ABC transporter ABCA1 plays a key role in the first steps of the reverse cholesterol transport pathway by mediating lipid efflux from macrophages. Previously, it was demonstrated that human ABCA1 overexpression in vivo in transgenic mice results in a mild elevation of plasma HDL levels and increased efflux of cholesterol from macrophages. In this study, we determined the effect of overexpression of ABCA1 on atherosclerosis development. Human ABCA1 transgenic mice (BAC(+)) were crossed with ApoE(-/-) mice, a strain that spontaneously develop atherosclerotic lesions. BAC(+)ApoE(-/-) mice developed dramatically smaller, less-complex lesions as compared with their ApoE(-/-) counterparts. In addition, there was increased efflux of cholesterol from macrophages isolated from the BAC(+)ApoE(-/-) mice. Although the increase in plasma HDL cholesterol levels was small, HDL particles from BAC(+)ApoE(-/-) mice were significantly better acceptors of cholesterol. Lipid analysis of HDL particles from BAC(+)ApoE(-/-) mice revealed an increase in phospholipid levels, which was correlated significantly with their ability to enhance cholesterol efflux. Show less