Abstract
APOC3 has been focused as an emerging therapeutic target beyond LDL. ApoC-III circulates in blood on TG-rich lipoprotein and also on HDL. ApoC-III inhibits LPL activity that is essential for HDL maturation. We investigated the roles of plasma apoC-III on HDL-lipid composition beyond simple HDL-C. Methods: Fasting lipid profiles without lipid drugs were analyzed by ultracentrifugation, and free cholesterol (FC), cholesterol ester (CE), triglycerides (TG) and phospholipids (PL) levels in each fraction were determined. 500 patients (285 males, age 56±18 ys, TC 225±51, TG 168±146, HDL-C 50±15 mg/dL) with primary dyslipidemia (Dyslipidemia Group), and also 171 patients (96 males, age 39±19, TC 338±60, TG 126±98, HDL-C 49±15) with genetically confirmed heterozygous familial hypercholesterolemia (FH Group) were analyzed. Coronary stenosis index (CSI) was estimated with angiography in 195 patients (125 males, age 62±11) in Dyslipidemia and 54 patients (29 males, age 53±14) in FH Group. Results: ApoC-III correlated with TG, LDL-C, fasting glucose, and BMI in both groups as previously reported. Plasma apoC-III levels were slightly higher in Dyslipidemia Group (12±7 vs. 11±4 mg/dL, p <0.01). ApoC-III did not correlate with HDL-C, but negatively correlated with apoAI/AII ratio in Dyslipidemia Group (R 2 15%, p <0.0001). In HDL composition, apoC-III strongly correlated with HDL-TG/HDL-PL ratio (R 2 30%, p <0.0001) rather than HDL-TG (R 2 25%, p <0.0001). ApoC-III did not correlated with HDL-FC, HDL-CE, or HDL-PL, but negatively correlated with HDL-FC/HDL-PL (R 2 9%, p <0.0001) in Dyslipidemia Group. These data may suggest the participant of apoC-III in disturbance of HDL maturation. Intriguingly, apoC-III did not correlate with HDL-TG/HDL-PL or HDL-FC/HDL-PL in FH Group. In angiographic analysis, HDL-TG/HDL-PL ratio strongly correlated with CSI (R 2 10%, p <0.0001) rather than TG (R 2 3%, p <0.05) or HDL-TG (R 2 3%, p <0.05). Highest quartile of apoC-III showed significantly higher CSI compared with other quartiles ( p <0.05) in Dyslipidemia Group. No such tendency was observed in FH Group. Conclusion: Plasma apoC-III strongly correlated with malignant HDL-lipid composition strongly associated with coronary artery disease in patients with primary dyslipidemia.
Published Version
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