Dongliang Wang1, Xiao Yan1, Min Xia1, Yan Yang1, Dan Li1, Xinrui Li1, Fenglin Song1, Wenhua Ling2. 1. From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.). 2. From the Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., X.Y., M.X., Y.Y., D.L., X.L., F.S., W.L.); and Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus), Guangzhou, Guangdong Province, People's Republic of China (D.W., M.X., Y.Y., D.L., W.L.). lingwh@mail.sysu.edu.cn.
Abstract
OBJECTIVE: Recent studies have shown the role of miRNAs in macrophage reverse cholesterol transport and atherogenesis. We hypothesized that coenzyme Q10 (CoQ10) may increase macrophage reverse cholesterol transport by regulating miRNA expression that contributes to the prevention of atherosclerosis. APPROACH AND RESULTS: CoQ10 treatment suppressed oxidized low-density lipoprotein-induced macrophage foam cell formation by ameliorating the binding of activator protein-1 to the putative promoter region of miR-378 primary transcript, thus decreasing the miR-378 level and enhancing the ATP-binding cassette transporter G1-mediated macrophage cholesterol efflux to high-density lipoprotein. Subsequently, the axis of activator protein-1/miR-378/ATP-binding cassette transporter G1 cholesterol efflux was confirmed in peritoneal macrophages isolated from CoQ10-treated apolipoprotein E-deficient mice. Finally, CoQ10 consumption promoted macrophage reverse cholesterol transport and inhibited the progression of atherosclerosis in apolipoprotein E-deficient mice. CONCLUSIONS: This study identified activator protein-1/miR-378/ATP-binding cassette transporter G1 as a novel cascade for CoQ10 in facilitating macrophage cholesterol efflux in vitro and in vivo. Our data thus imply that both CoQ10 and miR-378 are promising candidates for atherosclerosis prevention and treatment.
OBJECTIVE: Recent studies have shown the role of miRNAs in macrophage reverse cholesterol transport and atherogenesis. We hypothesized that coenzyme Q10 (CoQ10) may increase macrophage reverse cholesterol transport by regulating miRNA expression that contributes to the prevention of atherosclerosis. APPROACH AND RESULTS:CoQ10 treatment suppressed oxidized low-density lipoprotein-induced macrophage foam cell formation by ameliorating the binding of activator protein-1 to the putative promoter region of miR-378 primary transcript, thus decreasing the miR-378 level and enhancing the ATP-binding cassette transporter G1-mediated macrophage cholesterol efflux to high-density lipoprotein. Subsequently, the axis of activator protein-1/miR-378/ATP-binding cassette transporter G1 cholesterol efflux was confirmed in peritoneal macrophages isolated from CoQ10-treated apolipoprotein E-deficientmice. Finally, CoQ10 consumption promoted macrophage reverse cholesterol transport and inhibited the progression of atherosclerosis in apolipoprotein E-deficientmice. CONCLUSIONS: This study identified activator protein-1/miR-378/ATP-binding cassette transporter G1 as a novel cascade for CoQ10 in facilitating macrophage cholesterol efflux in vitro and in vivo. Our data thus imply that both CoQ10 and miR-378 are promising candidates for atherosclerosis prevention and treatment.
Authors: Dimitry A Chistiakov; Alexandra A Melnichenko; Veronika A Myasoedova; Andrey V Grechko; Alexander N Orekhov Journal: J Mol Med (Berl) Date: 2017-08-07 Impact factor: 4.599
Authors: Juan M Suárez-Rivero; Carmen J Pastor-Maldonado; Suleva Povea-Cabello; Mónica Álvarez-Córdoba; Irene Villalón-García; Marta Talaverón-Rey; Alejandra Suárez-Carrillo; Manuel Munuera-Cabeza; José A Sánchez-Alcázar Journal: Biomedicines Date: 2021-03-05