Jiatian Wu, n/a
MD
Department of Intensive Care Unit, the Second Hospital of Anhui Medical University, Hefei, China; the Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei，China
hefei, United States
Disclosure information not submitted.
Title: Protective Effects of Ivabradine on H9c2 Myocardial Cells Induced by Ischemia/Reperfusion Injury
Introduction: Ivabradine, a heart rate reducing agent, is nowadays recommended for patients with stable angina and chronic heart failure according to current guidelines in many countries. Recently, beneficial effects of ivabradine on anti-ischemia/reperfusion(I/R) injury are progressively emerging. However, the mechanism underlying is not completely understood. The present study investigated the effects and mechanisms underlying ivabradine in I/R-induced cardiomyocyte oxidative stress and apoptosis.
Methods: Hypoxia/reoxygenation (H/R) ‑treated H9c2 myocardial cells were used as an in vitro Ischemia/reperfusion injury model. H9c2 were treated with or without ivabradine (20μM or 100μM) or PI3-kinase inhibitor LY294002(10μM) for 12 hours and then subjected to 12 hours of hypoxia and 24 hours of reoxygenation. Hypoxia was achieved by a hypoxia chamber filled with 5%CO2 and 95% N2 at 37℃. Cell viability were assessed by Cell Counting Kit-8 assay. Cell apoptosis were detected by flow cytometry and staining was performed using anenxin V-FITC/PI. The amount of Superoxide Dismutase (SOD) and Malondialdehyde (MDA) was measured by SOD assay kit and MDA assay kit. The expressions of Caspase-3 and mTOR were determined by Western-blot assay.
Results: A decrease of cell viability and an increase rate of apoptosis occurred after H/R. Consistently, the activity of SOD in H9C2 of H/R was lower and the amount of MDA was higher. Significant improvement was noted in cells treated with ivabradine compared to H/R. Ivabradine upregulated the expression levels of pmTOR/mTOR and downregulated the expression levels of pro-apoptotic proteins cleaved Caspase-3. LY294002 antagonized the effects of ivabradine on apoptosis.
Conclusions: Ivabradine may protect H9c2 cardiomyocytes against I/R injury by reducing apoptosis and oxidative stress via activation of the PI3K/Akt/mTOR signaling pathway. The Results of the present study indicate the potential therapeutic benefits of ivabradine in the treatment of myocardial I/R injury.