Role of cholesterol in cardiovascular dysfunction

Abstract

Background: Hypercholesterolemia, which is characterized by high levels of lipoprotein-containing cholesterol in plasma, is generally accepted as a major risk factor for the development of atherosclerosis and subsequent myocardial ischemia. The cardiovascular effects of elevated serum cholesterol are predominantly attributed to atherosclerotic lesions in coronary arteries; however, the role of cholesterol in causing heart dysfunction without the occurrence of atherosclerosis is not fully appreciated.

Observations: Each type of biological membrane has a specific amount of cholesterol, which is required for proper functioning of the membrane-bound enzymes and cation transporters. High levels of cholesterol have been demonstrated to cause changes in membrane structure and function independent of atherosclerosis. Particularly, alterations in membrane cholesterol content have been shown to affect myocardial contractility, excitability and conduction properties. The activities of cardiac sarcolemmal enzymes such as Na+-K+ ATPase, Mg2+ ATPase and Ca2+ pump ATPase as well as Ca2+-dependent K+ channels and Na+-Ca2+ exchanger are altered as a consequence of changes in the membrane cholesterol content. Furthermore, high levels of cholesterol are known to cause endothelial dysfunction and smooth muscle abnormalities, which occur without visible atherosclerosis lesion development. On the other hand, indirect effects of cholesterol on the cardiovascular system are evident on its oxidative modification and subsequent development of visible atherosclerotic lesions and myocardial ischemia.

Conclusions: Hypercholesterolemia has been shown to cause cardiovascular dysfunction due to direct action on membrane fluidity, enzyme activities and cation transporters in the endothelial cells, vascular smooth muscle cells and cardiomyocytes. On the other hand, development of atherosclerosis by high levels of cholesterol is associated with the oxidation products of cholesterol and is thus considered to affect the cardiovascular system indirectly as a consequence of ischemic heart disease.