Details

Autor(en) / Beteiligte

• Csiszar, Anna
• Labinskyy, Nazar
• Pinto, John T
• Ballabh, Praveen
• Zhang, Hanrui
• Losonczy, Gyorgy
• Pearson, Kevin
• de Cabo, Rafael
• Pacher, Pal
• Zhang, Cuihua
• Ungvari, Zoltan

Titel

Resveratrol induces mitochondrial biogenesis in endothelial cells

Ist Teil von

• American journal of physiology. Heart and circulatory physiology, 2009-07, Vol.297 (1), p.H13-H20

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Departments of 1 Physiology, 2 Biochemistry, and 3 Cell Biology and Anatomy and Pediatrics, New York Medical College, Valhalla, New York; 4 Department of Internal Medicine, Medical Pharmacology and Physiology and Nutritional Sciences, University of Missouri, Columbia, Missouri; 5 Department of Pulmonology, Semmelweis University, Hungary; 6 Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore; and 7 Laboratory of Physiological Studies, Section on Oxidative Stress Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; and 8 Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma Submitted 16 April 2009 ; accepted in final form 4 May 2009 Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1 , nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases. vasoprotection; histone deacetylase; endothelial dysfunction; diabetes; obesity Address for reprint requests and other correspondence: Z. Ungvari, Dept. of Physiology, New York Medical College, Valhalla, NY 10595 (e-mail: zoltan_ungvari{at}nymc.edu )