Journal article
Hydralazine protects the heart against acute ischaemia/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission
SB Kalkhoran, J Kriston-Vizi, S Hernandez-Resendiz, GE Crespo-Avilan, AA Rosdah, JG Lees, JRSD Costa, NXY Ling, JK Holien, P Samangouei, K Chinda, EP Yap, JA Riquelme, R Ketteler, DM Yellon, SY Lim, DJ Hausenloy
Cardiovascular Research | OXFORD UNIV PRESS | Published : 2022
DOI: 10.1093/cvr/cvaa343
Abstract
Aims: Genetic and pharmacological inhibition of mitochondrial fission induced by acute myocardial ischaemia/reperfusion injury (IRI) has been shown to reduce myocardial infarct size. The clinically used anti-hypertensive and heart failure medication, hydralazine, is known to have anti-oxidant and anti-apoptotic effects. Here, we investigated whether hydralazine confers acute cardioprotection by inhibiting Drp1-mediated mitochondrial fission. Methods and results: Pre-treatment with hydralazine was shown to inhibit both mitochondrial fission and mitochondrial membrane depolarisation induced by oxidative stress in HeLa cells. In mouse embryonic fibroblasts (MEFs), pre-treatment with hydralazine..
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Awarded by Medical Research Council
Funding Acknowledgements
This work was funded in part by Stafford Fox Medical Research Foundation (to S.Y.L.) and infrastructure funding from the Victorian Government (Australia) Operational Infrastructure Support Scheme to St Vincent's Institute of Medical Research. J.K.H. is a 5 Point Foundation Christine Martin Fellow at St Vincent's Institute, and is now a Vice Chancellors Fellow at RMIT University. J.A.R. is funded by Agencia Nacional de Ciencia y Desarrollo (Chile), FONDECYT 11181000 and FONDAP 15130011. This work was supported by the Medical Research Council Core funding to the MRC LMCB (MC_U12266B). D.J.H. was supported by the British Heart Foundation (CS/14/3/31002), the National Institute for Health Research University College London Hospitals Biomedical Research Centre, Duke-National University Singapore Medical School, Singapore Ministry of Health's National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (NMRC/CSA-SI/0011/2017) and Collaborative Centre Grant scheme (NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2016-T2-2-021). This article is based upon work from COST Action EU-CARDIOPROTECTION CA16225 supported by COST (European Cooperation in Science and Technology).