Impact of conditioning hyperglycemic on myocardial infarction rats: Cardiac cell survival factors

Abstract

While clinical data have suggested that the diabetic heart is more susceptible to ischemic heart disease (IHD), animal data have so far pointed to a lower probability of IHD. Thus, the aim of this present review is to look at these conflicting results and discuss the protective mechanisms that conditioned hyperglycemia may confer to the heart against ischemic injury. Several mechanisms have been proposed to explain the cardioprotective action of high glucose exposure, namely, up-regulation of anti-apoptotic factor Bcl-2, inactivation of pro-apoptotic factor bad, and activation of pro-survival factors such as protein kinase B (Akt), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α and protein kinase C-ε. Indeed, cytosolic increase in Ca²⁺ concentration, the mitochondrial permeability transition pore, plays a key role in the genesis of ischemic injury. Previous studies have shown that the diabetic heart decreased Na⁺/Ca²⁺ and Na⁺/H⁺ exchanger activity and as such it accumulates less Ca²⁺ in cardiomyocyte, thus preventing cardiac injury and the associated heart dysfunctions. In addition, the expression of VEGF in diabetic animals leads to increased capillary density before myocardial infarction. Despite poor prognostic in the long-term, all these results suggest that diabetes mellitus and consequently hyperglycemia may indeed play a cardioprotective role against myocardial infarction in the short term.

Keywords: Conditioned hyperglycemia; Diabetes mellitus; Myocardial infarction; Cardioprotection; Survival factors

Core tip: Hyperglycemia or diabetes triggers a conditioned state that may protect the heart against ischemic injury and associated detrimental effects. These beneficial effects are present in short term diabetes and/or moderate hyperglycemia. The increase in glucose availability, the preferred energy substrate of the heart in stress condition, is likely to be one of the main cardioprotector mechanisms of hyperglycemia. However, other cardioprotective mechanisms seem to be involved, such as the release of cellular survival factors, ions preventing overload and angiogenesis. A fuller understanding of the mechanisms underlying conditioned hyperglycemia is then critical for the development of effective therapeutic strategies against ischemic heart disease.