Malfitano Christiane, de Souza Junior Alcione Lescano, Irigoyen Maria Cláudia
Christiane Malfitano, Laboratório de Fisiologia Translacional, UNINOVE, 01504001 São Paulo, Brazil.
World J Cardiol. 2014 Jun 26;6(6):449-54. doi: 10.4330/wjc.v6.i6.449.
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 Ca(2+) 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(+)/Ca(2+) and Na(+)/H(+) exchanger activity and as such it accumulates less Ca(2+) 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.
虽然临床数据表明糖尿病心脏更容易患缺血性心脏病(IHD),但迄今为止动物实验数据却显示IHD的发病概率较低。因此,本综述的目的是审视这些相互矛盾的结果,并探讨高血糖状态下可能赋予心脏抵抗缺血性损伤的保护机制。人们提出了几种机制来解释高糖暴露的心脏保护作用,即抗凋亡因子Bcl-2的上调、促凋亡因子Bad的失活以及蛋白激酶B(Akt)、血管内皮生长因子(VEGF)、缺氧诱导因子-1α和蛋白激酶C-ε等促生存因子的激活。实际上,胞质Ca(2+)浓度的增加,即线粒体通透性转换孔,在缺血性损伤的发生中起关键作用。先前的研究表明,糖尿病心脏的Na(+)/Ca(2+)和Na(+)/H(+)交换体活性降低,因此心肌细胞中Ca(2+)的蓄积减少,从而预防心脏损伤及相关的心脏功能障碍。此外,糖尿病动物体内VEGF的表达会导致心肌梗死前毛细血管密度增加。尽管长期预后不佳,但所有这些结果表明,糖尿病以及由此导致的高血糖在短期内可能确实对心肌梗死起到心脏保护作用。