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Mechanisms for Cardiac Dysfunction in the Metabolic Syndrome

E. Dale Abel

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Conference: 2008 International PHA Conference and Scientific Sessions

Release Date: 06.22.2008

Presentation Type: Slide Shows

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The metabolic syndrome represents a cluster of abnormalities such as obesity, insulin resistance, dyslipidemia and type 2 diabetes that increase the risk of developing cardiovascular diseases such as coronary artery disease and heart failure. The heart failure risk is increased even after adjusting for coronary artery disease and hypertension, and evidence is emerging that changes in cardiac energy metabolism might contribute to the development of contractile dysfunction. Recent data suggests that myocardial mitochondrial dysfunctionmay play an important role in the pathogenesis of cardiac contractile dysfunction in obesity, insulin resistance and type 2 diabetes. The presentation will review mechanisms that are responsible for mitochondrial dysfunction in the heart in the metabolic syndrome. The role of insulin resistance, oxidative stress and lipidoverload in leading to impaired mitochondrial respiratory capacity and fatty acid mediated mitochondrial uncoupling, all of which reduce ATP generation, will be discussed. The net result of these defects is a limitation in high-energy reserves within the heart that sensitizes the heart to injury in the context of superimposed stress such as myocardial hypertrophy and ischemia.