Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission |
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| Institution: | 1. Advanced Center for Chronic Diseases (ACCDiS), Centro Estudios Moleculares de la Célula (CEMC), Departamento Bioquímica y Biología Molecular, Facultad Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile;2. Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, United States;1. Chongqing Medical University, The First College of Clinical Medicine, Clinical Medicine of Grade 2012, Chongqing, China;2. Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Science & Sichuan Provincial People''s Hospital, Chengdu, China;3. Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;1. Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;2. Institute of Gerontology, The University of Tokyo, Tokyo, Japan;3. Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan;1. Department of Molecular Biology, Medical Biochemistry, and Pathology, Centre de recherche du CHU de Québec, Université Laval, Québec, Québec, Canada;2. Department of Medicine, Centre de recherche du CHU de Québec, Université Laval, Québec, Québec, Canada;3. Department of Molecular Medicine, Centre de recherche du CHU de Québec, Université Laval, Québec, Québec, Canada;4. Center for Excellence in Pulmonary Biology, Stanford University, Stanford, California, USA;1. Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Tohon, Japan;2. Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University, Graduate School of Medicine, Tohon, Japan;3. Department of Pediatrics, Ehime University, Graduate School of Medicine, Tohon, Japan |
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| Abstract: | Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production. Disruption of mitochondrial structural integrity was also observed in a rat model of adenine-induced aortic calcification. Increased production of reactive oxygen species, enhanced expression and phosphorylation of Drp1, and excessive mitochondrial fragmentation were also observed in Pi-treated VSMCs. These effects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol and subsequent activation of caspase-3. Quercetin was shown to block Pi-induced apoptosis and calcification of VSMCs by inhibiting oxidative stress and decreasing mitochondrial fission by inhibiting the expression and phosphorylation of Drp1. Quercetin also significantly ameliorated adenine-induced aortic calcification in rats. In summary, our findings suggest that quercetin attenuates calcification by reducing apoptosis of VSMCs by blocking oxidative stress and inhibiting mitochondrial fission. |
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