Should trans fatty acids be viewed as membrane-active drugs.pdfVIP

Atherosclerosis Supplements 7 (2006) 41–42 Should trans fatty acids be viewed as membrane-active drugs? Arnold M. Katz ? The Cardiology Division, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, United States Abstract Trans fatty acids (TFA) can modify cellular function by interacting with hydrophobic regions of membrane proteins. Because these interactions resemble those of pharmacological agents, it might be appropriate to view TFA as drugs. ? 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Arrhythmia; Diet; Heart disease; Lipids; Trans fatty acids A role for dietary lipids in the pathogenesis of sudden cardiac death became apparent more than 30 years ago, when ventricular arrhythmias after myocardial infarction were found to be more severe when circulating free fatty acid (FFA) levels were elevated [1]. These observations stimulated experimental studies which demonstrated that the arrhythmogenic potencies of different fatty acids are in?uenced by the structure of the lipid, notably the length and saturation of the fatty acyl chain [2–5]. Conversely, dietary n-3 polyunsaturated fatty acids have been reported to reduce the incidence of sudden cardiac death [6]. The pro- and antiarrhythmic effects of dietary fatty acids are probably due to interactions with biological membranes. The latter are lined by charged hydrophilic (lipophobic) head groups and contain a hydrophobic (lipophilic) core, made up of cholesterol and the fatty acyl chains of the membrane lipids, that is virtually impermeable to charged molecules (Fig. 1). Most biological activities of membranes are mediated by proteins imbedded in the bilayer; these include enzymes, receptors, carriers, pumps, and the voltage-gated ion channels responsible for the cardiac action potential. A mechanism by which dietary fats might in?uence the appearance of cardiac arrhythmias was suggested more than a quarter century ago, when hydrophobic moieties in the core of the bil