Contribution of apoptosis in myocardial reperfusion injury and loss of cardioprotection in diabetes mellitus

Abstract

Ischemic heart disease is one of the major causes of death worldwide. Ischemia is a condition in which blood flow of the myocardium declines, leading to cardiomyocyte death. However, reperfusion of ischemic regions decreases the rate of mortality, but it can also cause later complications. In a clinical setting, ischemic heart disease is always coincident with other co-morbidities such as diabetes. The risk of heart disease increases 2-3 times in diabetic patients. Apoptosis is considered to be one of the main pathophysiological mechanisms of myocardial ischemia-reperfusion injury. Diabetes can disrupt the anti-apoptotic intracellular signaling cascades involved in myocardial protection. Therefore, targeting these changes may be an effective cardioprotective approach in the diabetic myocardium against ischemia-reperfusion injury. In this article, we review the interaction of diabetes with the pathophysiology of myocardial ischemia-reperfusion injury, focusing on the contribution of apoptosis in this context, and then discuss the alterations of pro-apoptotic or anti-apoptotic pathways probably responsible for the loss of cardioprotection in diabetes.

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia–reperfusion injury through iNOS inhibition in hyperthyroid rats

“…It has been reported that an increase in Bcl-2 expression decreases the rate of ATP consumption during ischemia and reduces IR-induced apoptosis, which during IR injury can cause cardiac dysfunction; prevention of apoptosis could be considered as a new aim for cardioprotection against IR injury (Badalzadeh et al, 2015). It has been previously shown that IPost showed an antiapoptotic effect on the heart (Xing et al, 2008), a finding observed in our control group as well.…”

Modulation of hippocampal gene expression of microRNA-146a/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats

“…[23] Administration of troxerutin has reversed the excitotoxic brain damage and improved memory and cognitive impairment in the hippocampus of nondiabetic mice[13] and enhanced the spatial learning in rats. [20] However, the underlying mechanisms of these protective actions of troxerutin have not been yet fully understood.…”

Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy: the case for repeat application as a novel therapy for lower extremity ulceration

“…These include impaired kinase and signalling pathways. Specifically, these are altered extracellular signal-regulated kinase (ERK) 1/2 [116, 117], decreased phosphorylation of glycogen synthase kinase-3 beta [117, 118], impaired [112, 113, 117] or chronic [114] Akt phosphorylation and Akt activity [119], effects on mitochondrial adenosine triphosphate (ATP)-dependent potassium channels [106, 120–124], decreased CGRP [125], reduced adenosine [108], altered bioavailability of NO [126] and abnormalities of other apoptotic pathways [127, 128]. In a human RIPC diabetes study, raised O -linked β- N -acetylglucosamine was found to be associated with a state of chronic cardioprotection, with subsequent RIPC providing no additional benefit [129].…”