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(Circulation Research. 2007;100:795.)
© 2007 American Heart Association, Inc.

Reviews

Defective Mitochondrial Biogenesis

A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome?

Enzo Nisoli, Emilio Clementi, Michele O. Carruba, Salvador Moncada

From the Department of Pharmacology, Chemotherapy and Medical Toxicology (E.N., M.O.C.), School of Medicine, Milan University, Italy; Istituto Auxologico Italiano (E.N., M.O.C.), Italy; Department of Preclinical Sciences (E.C.), Laboratorio Interdisciplinare Tecnologie Avanzate Vialba, Milan University, Italy; E. Medea Scientific Institute (E.C.), Bosisio Parini, Italy; and The Wolfson Institute for Biomedical Research (S.M.), University College London, UK.

Correspondence to Enzo Nisoli, MD, PhD, Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, Milan University, Via Vanvitelli, 32-20129 Milan, Italy; E-mail enzo.nisoli{at}unimi.it; or Salvador Moncada, FRCP, FRS, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK; E-mail: s.moncada@ucl.ac.uk

This Review is part of a thematic series on the Role of Mitochondria in Cardiovascular Diseases, which includes the following articles:

Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome?

Mitochondrial Dysfunction in Atherosclerosis

Free Radicals, Mitochondria, and Oxidized Lipids: The Emerging Role in Signal Transduction in Vascular Cells

Mitochondrial Biology and Vascular Biology

Role of Mitochondria in Insulin Resistance
Marshall S. Runge Guest Editor

The metabolic syndrome is a group of risk factors of metabolic origin that are accompanied by increased risk for type 2 diabetes mellitus and cardiovascular disease. These risk factors include atherogenic dyslipidemia, elevated blood pressure and plasma glucose, and a prothrombotic and proinflammatory state. The condition is progressive and is exacerbated by physical inactivity, advancing age, hormonal imbalance, and genetic predisposition. The metabolic syndrome is a particularly challenging clinical condition because its complex molecular basis is still largely undefined. Impaired cell metabolism has, however, been suggested as a relevant pathophysiological process underlying several clinical features of the syndrome. In particular, defective oxidative metabolism seems to be involved in visceral fat gain and in the development of insulin resistance in skeletal muscle. This suggests that mitochondrial function may be impaired in the metabolic syndrome and, thus, in the consequent cardiovascular disease. We have recently found that mitochondrial biogenesis and function are enhanced by nitric oxide in various cell types and tissues, including cardiac muscle. Increasing evidence suggests that this mediator acts as a metabolic sensor in cardiomyocytes. This implies that a defective production of nitric oxide might be linked to dysfunction of the cardiomyocyte metabolism. Here we summarize some recent findings and propose a hypothesis for the high cardiovascular risk linked to the metabolic syndrome.

Key Words: nitric oxide • mitochondrial biogenesis • peroxisome proliferator-activated receptor- coactivator 1 • cardiomyocytes • obesity

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