Journal of Pharmacovigilance

Aliskiren attenuated hypoxia-induced cardiac injury through activation of autophagy

Conference Series LLC Joint International Event on 7^th Pharmacovigilance & Pharmaceutical Industry

August 22-24, 2016 Vienna, Austria

Yuh Lien Chen

National Taiwan University, Taiwan

Posters & Accepted Abstracts: J Pharmacovigil

Abstract:

Aliskiren is a direct renin inhibitor that has been effective in attenuating hypertension. The aim of this study was to determine whether aliskiren could protect the ischemia-induced myocardial infarction (MI) and elucidate the mechanisms of action. C57J/ BL6 mice were subjected to the ligation of left anterior coronary artery and were treated for 14 days with vehicle or aliskiren (25 mg/ Kg/day via a subcutaneous injection), whereas sham-operated animals served as controls. Aliskiren improved systolic and diastolic LV function and improved cardiac morphology compared with PBS-treated mice after MI. This was associated with the number of TUNEL-positive cells. Aliskiren increased autophagy assayed by LC3B-II expression and transmission electron microscopy. Furthermore, we employed H9c2 cardiomyocytes as a cell model to investigate the effects of aliskiren on apoptosis and autophagy in cardiomyocytes under hypoxia-induced injury of cardiomyocytes. H9c2 cells were treated with 1-20 mM aliskiren for 24 h under normoxia, none of which had significant effect on the cell viability by MTT assay. 80% of cells died after hypoxia for 16 h, while aliskiren treatment rescued cell death in a dose-dependent manner. In all subsequent experiments, unless otherwise specified, 20 μM aliskiren was used. The beneficial effects of aliskiren were associated with the decrease of apoptosis and the increase of autophagy by increased autophagosomes. Taken together, our findings revealed that aliskiren increased cardiomyocyte survival through the increased autophagosomal formation.

Biography :

Yuh Lien Chen has completed her PhD from National Taiwan University. She is a Professor of Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University. She has published more than 80 papers in reputed journals.

Email: ylchenv@ntu.edu.tw