Abstract
Valvular heart disease (VHD) is an active process involving a wide range of pathological changes. The major complications of VHD are stenosis and regurgitation, which are macroscopic phenomena, induced in part through cellular changes. Altered expression of mitochondria associated genes causes membrane potential depolarization, leading to the increased levels of apoptosis observed in cardiac dysfunction. Objective of this study is to find molecular medicine candidates that can control expression of the key mitochondria apoptosis regulatory genes. Present study aims to assess the way microRNA are involved in regulating mitochondrial apoptosis regulatory genes and observation of their expression in the heart valve dysfunction. Apoptotic genes PUMA and DRP1 were found to be highly expressed, whereas anti-apoptotic gene ARC was down regulated. The expression level of GATA-4 transcription factor was also reduced in cardiac valve tissues. MicroRNAs miR-15a and miR-29a were repressed, while miR-214 was up regulated. Furthermore, study showed that PUMA, DRP1 and ARC expression might be attenuated by their respective miRNAs. Our results indicate that mitochondria regulatory genes might be controlled by miR-15a, miR-29a and miR-214, in VHD patients. Present study may provide platform for future research regarding potential therapeutic role of miRNAs in CVDs.
•Disruption of mitochondrial membrane regulatory genes lead to apoptosis during cardiac valve dysfunction.•Pro-apoptotic PUMA and DRP1 are up regulated while anti-apoptotic ARC is down regulated in stenosis and regurgitation.•The expression of GATA-4 transcription factor is reduced in valve dysfunction during apoptosis.•miR-15a and miR-29a are repressed, while miR-214 is up regulated.•The level of ROS is high with reduced level of antioxidant enzymatic activities of SOD and CAT in VHD.