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Diane Bick Ph.D. Address and Contact: |
Current Research Interests
Regulation of Fatty Acid Metabolism in the Cardiac Myocyte
In a normal heart most of the energy requirement for contraction is provided by the oxidation of long chain fatty acids. Following a myocardial infarction high levels of circulating fatty acids are often observed and cardiac fatty acid oxidation increases upon reperfusion of ischemic tissue. This rapid recovery of fatty acid oxidation results in an increased contribution of fatty acid oxidation to ATP production in the myocyte. However, this increased reliance upon fatty acid oxidation has a detrimental effect on the functional recovery of the myocardium. Following severe ischemia, when fatty acid oxidation is high, mechanical function is depressed suggesting that some components of the fatty acid oxidation pathway may be altered in the post-ischemic tissue. The goal of this research is to understand the physiological control of fatty acid metabolism in the heart under normal and pathological conditions. Several studies have indicated that malonyl-CoA is an important regulator of cardiac fatty acid oxidation. There is a close relationship between cardiac malonyl-CoA levels and fatty acid oxidation in both isolated cardiac myocytes and perfused hearts. This relationship raises the possibility that a decrease in tissue malonyl CoA levels may be responsible for the increase in fatty acid oxidation observed in reperfused, ischaemic tissue. Malonyl-CoA is produced following the carboxylation of acetyl-CoA by the enzyme acetyl-CoA carboxylase (ACC). Regulation of ACC phosphorylation in the liver has been well described and the major kinase responsible for the phosphorylation, and hence inactivation, of this protein is a 5¢ AMP dependent protein kinase (AMPK). The activity of AMPK has not been extensively studied in the heart. We have recently measured AMPK activity in the isolated neonatal rat myocyte. We wish to test the hypothesis that control of malonyl CoA production in the cardiac myocyte is consistent with the regulation of ACC by AMPK. Furthermore the activity of the AMPK may be regulated in part by the availability of fatty acyl CoA within the myocyte.
Certain fatty acids have recently been demonstrated to cause cells, including myocytes, to enter into apoptosis. We are currently also studying the mechanism by which exogenous fatty acids can induce a neonatal cardiac myocyte to become apoptotic. This information may contribute to our understanding to the cardiovascular changes associated with acute diseases like ischaemia and other more chronic diseases like diabetes.
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