Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase... : Journal of Cardiovascular Medicine (original) (raw)

Working hypothesis

Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition on serum matrix metalloproteinase-13 and tissue inhibitor matrix metalloproteinase-1 levels as a sign of plaque stabilization

Cevik, Cihan; Otahbachi, Mohammad; Nugent, Kenneth; Warangkana, Chokesuwattanaskul; Meyerrose, Gary

aTexas Tech University Health Sciences Center, Internal Medicine Department, USA

bTexas Tech University Health Sciences Center, Cardiology Department, Lubbock, Texas, USA

Received 23 June, 2008

Revised 28 July, 2008

Accepted 27 August, 2008

Correspondence to Cihan Cevik, MD, Texas Tech University Health Sciences Center, Internal Medicine Department, 3601 4th Street, Lubbock, TX 79430, USA Tel: +1 806 7433155; e-mail: [email protected]

Abstract

Atherosclerotic plaques are composed of a lipid rich core, which is covered by a collagen rich fibrous cap. Rupture of the atherosclerotic plaque with superimposed thrombosis is the main cause of acute coronary syndromes, including acute myocardial infarction and unstable angina. The stability of the plaque depends on its collagen content; degradation of the collagen leads to a vulnerable plaque that is prone to rupture. Recent studies have demonstrated a critical role for matrix metalloproteinases (MMPs) in the degradation of the collagen content and the reduction of mechanical stability of the atherosclerotic plaques. Increased expression of various MMPs has been shown in the tissue sections of atherosclerotic plaques. The increased expression of MMPs in the atheroma also leads to increased MMP levels in the circulation. The cholesterol lowering drugs – 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) – decrease the tissue expression of various MMPs in atheromatous plaques by attenuating the inflammatory process that promotes MMP expression during the course of atherosclerosis. However, the effect of statin treatment on the serum levels of MMP-13, which has a critical role in the initiation of collagen degradation, is unknown. On the basis of these previous studies, we discuss the need for studies on the effect of statin treatment on the serum levels of MMP-13 and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels in hypercholesterolemic patients.