5.Adaptive Mechanisms in the Diabetic Myocardium: An Alternative form of Endogenous Cardioprotection and its Loss

摘要

Summary High glucose (HG) is one of the factors determining the outcome of myocardial ischemic insult. However, it is still not clear whether it is casually related to a decreased ischemic tolerance in diabetic patients. In contrast to clinical and epidemiological studies demonstrating a higher risk of cardiovascular disorders in the diabetics, experimental data are not unequivocal and suggest that besides higher myocardial vulnerability, diabetes mellitus may be associated with induction of adaptive processes leading to paradoxically lower susceptibility to ischemia. It has been proposed that this phenomenon might share some molecular pathways with short-term endogenous protection (preconditioning) against ischemia/reperfusion injury in non-diseased heart. This chapter reviews some controversial findings of enhanced resistance to ischemia in the diabetic heart that stem from the experimental studies in different models of myocardial ischemia/ reperfusion injury. Specifically, it addresses the issue of potential mechanisms of increased resistance to ischemia in the experimental model of streptozotocin-induced diabetes. A particular focus has been drawn to the role of reactive oxygen species and hyperglycemia as some of the stressful factors, as well as to the cell signalling mechanisms mediated by "pro-survival" cascades of protein kinases, in relation to the mechanisms of classical ischemic preconditioning. Finally, mechanisms involved in suppression of protection in the diabetic myocardium including the effect of concomitant pathology, such as hypercholesterolemia, are also discussed.