Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium.

A ROLE for abnormal lipid metabolism in the pathogenesis of atherosclerosis was suggested over a century ago, when Virchow proposed that transport of plasma lipids into the walls of blood vessels contributed to the development of atheromatous lesions. Lipid abnormalities are now firmly established as one factor leading to ischemic heart disease, although the mechanism by which they lead to coronary artery occlusion remains incompletely understood. More recently, abnormalities of lipid metabolism have been implicated in another quite different aspect of the pathogenesis of ischemic heart disease. A large body of evidence now indicates that altered lipid metabolism can alter cardiac function by changing the properties of cardiac cell membranes, and that these functional changes may contribute to the decline in myocardial contractility, the arrhythmias, and the eventual cell death that follow coronary artery occlusion. This article will review some of these disorders in lipid metabolism and possible mechanisms by which they might modify membrane function in the ischemic heart. Disorders of Lipid Metabolism in the Ischemic Heart There are now at least three well-defined mechanisms by which lipid metabolism may be altered in the heart after coronary artery occlusion (Table 1). Each of these mechanisms has been implicated in the pathogenesis of the cardiac abnormalities seen in patients who sustain an acute myocardial infarction.