The effects of myocardial ischemic postconditioning on the levels of apoptotic genes Fas, Faslg, caspase 2 and microRNA-139-3P with reperfusion arrhythmias

Ischemic postconditioning (IPostC) is short I/R sections that are administered immediately after long-term ischemia and is considered as one of the strongest mechanisms limiting the size of myocardial infarction and reducing I/R injury. The aims of this study were to investigate proapoptotic genes Fas, Faslg, 45 alpha (Gadd45a) genes that cause growth arrest and DNA damage, an antiapoptotic gene Caspase 2 and microRNA-139-3p (miRNA-139-3p) on the I/R injury and to determine possible beneficial effects of IPostC on these genes. In addition, the effects of IPostC on oxidative stress-related malondialdehyde (MDA) levels, number of ventricular extrasystole in reperfusion and incidence of ventricular tachycardia were investigated. Sixty-six adult male Spraque Dawley rats weighing 300±50 g were used in the study. 7 min ischemia and 7 min reperfusion were applied for evaluation of MDA and arrhythmias. Molecular parameters associated with apoptotic pathway were evaluated by 30 min ischemia and 120 min reperfusion. IPostC was induced with 3 cycles of I/R (10 s each) after 30 min ischemia. ECG, blood pressure and heart rate were recorded throughout the experiment. MDA levels were determined by spectrophotometer, gene levels and miRNA-139-3p by qRT-PCR. MDA, Fas and Faslg genes were significantly increased with I/R compared to control group. Fas, Faslg, Gadd45a were significantly decreased and miRNA-139-3p increased significantly with IPostC treatment. Caspase 2 gene decreased significantly in I/R group (0,19±0,05) compared to control group (1,00±0,09), but increased significantly with IPostC application (0,36±0,05). In the I/R+IPostC group, the number of ventricular extrasystoles in reperfusion (3,86 ± 1,23) and the incidence of ventricular tachycardia (14,3%) were compared to the I/R group (25,29 ± 8,65; 51,9%, respectively) significantly decreased. IPostC may be thought to be protective of I/R injury by regulating apoptosis with the Fas, Faslg, Gadd45a, caspase 2 genes and related miRNA-139-3p. In addition to these features, IPostC application can prevent reperfusion arrhythmias. Keywords: Ischemic postconditioning, arrhythmia, apoptosis, miRNA-139-3p, Fas, Faslg, caspase 2.