Alterations of iron metabolism during heart ischemia/reperrfusion injury. Cytoprotective effects of Simvastatin.

Abstract

Ischemic heart disease, the main cause of mortality and morbidity in industrialized countries, is a metabolic phenomenon due to an inadequate oxygenation of heart tissue caused by the closing or narrowing of the coronary arteries. However, the ischemic condition and the subsequent tissue reperfusion, lead to several functional and metabolic changes that globally define the so-called “ischemia/reperfusion injury”. This injury leads to metabolic and functional alterations, in particular due to the production of the Oxygen Reactive Species (ROS) that are able to promote cell damage. Because iron is involved in the ROS production by the Haber-Weiss-Fenton reaction, the aim of this study was to elucidate the molecular mechanisms underlying the iron metabolism during the cardiac ischemia/reperfusion. To this aim it has been analyzed the activity and the expression of the main proteins involved in iron homeostasis, such as the Iron Regulatory Proteins, Transferrin Receptor 1 (TfR1), and ferritin in an in vivo model of cardiac ischemia/reperfusion.Other aim of this study has been to evaluate the cytoprotective role of the cholesterol-lowering drug Simvastatin, during the ischemic/reperfusion injury, because of its anti-inflammatory and antioxidant effects (“pleiotropic effects”).