Rosuvastatin enhances the catabolism of ldl apob-100 in subjects with combined hyperlipidemia in a dose dependent manner

• Main Authors: Ngoc Anh Le, Margaret R. Diffenderfer, Nuntakorn Thongtang, Esther M.M. Ooi, P. Hugh R. Barrett, Katalin V. Horvath, Gregory G. Dolnikowski, Bela F. Asztalos, Ernst J. Schaefer, W. Virgil Brown
• Other Authors: Atlanta VA Medical Center
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology; Chemistry
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/35463
• Institution: Mahidol University

© 2015 AOCS. Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB-100 production rate (PR), as well as increase apoB-100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB-100 in TRL and LDL and apoA-I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P < 0.0001), triacylglycerol by 14 % (ns) and 35 % (P < 0.01), apoB by 30 and 36 % (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA-I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB-100 FCR by 36 and 46 % (both ns) and LDL apoB-100 by 63 and 102 % (both P < 0.05), respectively. HDL apoA-I PR increased with low dose rosuvastatin (12 %, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB-100 PR or HDL apoA-I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB-100, with no significant effects on apoB-100 production or HDL apoA-I kinetics.