Further Studies On Myocardial Ischemia/reperfusion Injury And The Protective Role Of Ischemic Preconditioning

I. Expression of hypoxia-inducible factor-1αduring myocardial ischemia- reperfusion and its role in cardioprotection of ischemic preconditioningII. Effects of hyperlipoidemic atherosclerosis on myocardial ischemia-reperfusion injury and protective role of ischemic preconditioning in ratsIntroduction:Hypoxia plays a crucial role in the pathophysiological consequences induced by myocardial ischemia. Insufficient oxygen supply to the heart may cause cardiac dysfunction and then followed by cardiomyocyte apoptosis as well as necrosis. Therefore, oxygen homeostasis is critical in the maintenance of cardiac function and cardiomyocyte survival. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that regulates gene expression of various stress proteins involving in physiological and pathological adaptive responses to hypoxia. Understanding of the temporal and spatial pattern of expression of HIF-1 during myocardial ischemia- reperfusion may lead to the development of novel therapeutic strategies at gene level for the treatment of myocardial ischemia in humans.Furthermore, the mechanisms responsible for the protective role of ischemic preconditioning (IP) are not yet precisely clarified. It is of great interest to study whether HIF-1 is related to these mechanisms, because it is reported that HIF-1 may be the first molecular response to ischemia and induces gene expressions of many endogenous protective proteins that are implicated in the protective function of ischemic preconditioning.In addition, the majority of previous studies concerning the pathophysiology of ischemia-reperfusion (I/R) injury and the protective role of IP have been derived from animals with normal heart. Although the data derived from these studies provide meaningful insights into the mechanism of cellular injury after I/R and the protective role of IP, the relevance of these findings to those human patients with atherosclerotic heart remains unclear.Accordingly, in this article we studied the following two subjects.