Abstract
The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2) when diabetes mellitus (DM) rat heart was subjected to ischemia/reperfusion (I/R) intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH); cardiomyocyte in high glucose (HG) condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker), atractyloside (mitoPTP opener), and wortmannin (PI3K inhibitor) groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.
Highlights
Diabetes mellitus (DM) is a common metabolic disorder that can affect patient life and survival quality with acute and chronic complications [1,2,3]
In C I/ R group, compared with baseline, left ventricular developed pressure (LVDP), ±dp/dtmax, and rate-pressure product (RPP) were decreased, and left ventricular end diastolic pressure (LVEDP) was increased during ischemia period; during reperfusion period, LVDP, ±dp/dtmax, and RPP were lower and LVEDP was higher
During ischemia and reperfusion period, in contrast to C I/R rat, in DM I/R rat, LVDP, ±dp/dtmax, and RPP were decreased, and LVEDP was increased; compared with DM I/R group, LVDP, ±dp/dtmax, and RPP were increased, and LVEDP was decreased in DM + EtOH I/R group; compared with DM + EtOH I/R group, in DM + EtOH + CYA I/R group, LVDP, ±dp/dtmax, and RPP were furtherly decreased, and LVEDP was increased; the changes in DM + EtOH + Atr I/R and DM + EtOH + Wor I/R groups were similar to DM + EtOH + CYA I/R group (Table 1)
Summary
Diabetes mellitus (DM) is a common metabolic disorder that can affect patient life and survival quality with acute and chronic complications [1,2,3]. It is associated with a high cardiovascular mortality, and it is the most common cause of end-stage heart disease [4]. Myocardial ischemia/reperfusion (I/R) injury can cause cardiac glucose metabolism disorders, calcium overload, and cardiac fibrosis, resulting in accumulation of harmful products, leading to apoptosis and necrosis [5]. Previous studies indicated that, with the development of diabetes, cardiac ALDH2 activity was further decreased, and inhibition of Oxidative Medicine and Cellular Longevity
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