The endothelial-protective effects of HMG-CoA reductase inhibition in the setting of ischemia and reperfusion injury
Issue title: Selected Proceedings of the 15th Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM), June 28–July 1, 2009, Pontresina, Switzerland
Affiliations: From the Division of Cardiology, Mount Sinai and University Health Network Hospitals and Department of Pharmacology (A.L., M.L., J.D.P.), University of Toronto, Canada | Department of Cardiology (T.G.), University Medical Center of Mainz, Mainz, Germany
Note: [] Corresponding author: Tommaso Gori, MD, PhD, Department of Cardiology, University Medical Center of Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. E-mail: Tommaso.gori@ukmainz.de These authors equally contributed to the study.
Note: [] These authors equally contributed to the study.
Abstract: Animal studies have consistently demonstrated the ability of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors to limit the damage induced by ischemia-reperfusion (IR) in the cardiac, cerebral and mesenteric circulation through a mechanism dependent on the upregulation of cyclooxygenase-2 (COX-2). Our group performed studies aimed at investigating the mechanism of HMG-CoA reductase inhibitor-mediated endothelial protection from IR injury, in particular the role of COX-2, in a human in vivo model of IR-induced endothelial dysfunction. We demonstrated that HMG-CoA reductase inhibition protects against IR-induced endothelial damage, an effect that was lost upon COX-2 inhibition. These observations may suggest a mechanistic explanation for the cardioprotection observed in clinical settings such as percutaneous coronary interventions and coronary artery bypass surgery and may also propose a mechanistic hypothesis for the reported cardiotoxic effects of cyclooxygenase-2 inhibitors observed in clinical studies. These studies are summarized and discussed in the present paper.
