Journal article

Therapeutic Inhibition of Acid-Sensing Ion Channel 1a Recovers Heart Function After Ischemia-Reperfusion Injury

Meredith A Redd, Sarah E Scheuer, Natalie J Saez, Yusuke Yoshikawa, Han Sheng Chiu, Ling Gao, Mark Hicks, Jeanette E Villanueva, Yashutosh Joshi, Chun Yuen Chow, Gabriel Cuellar-Partida, Jason N Peart, Louise E See Hoe, Xiaoli Chen, Yuliangzi Sun, Jacky Y Suen, Robert J Hatch, Ben Rollo, Di Xia, Mubarak AH Alzubaidi Show all

CIRCULATION | LIPPINCOTT WILLIAMS & WILKINS | Published : 2021

Abstract

BACKGROUND: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly affects cardiac function. METHODS: We used genetic and pharmacologic methods to investigate the role of acid-sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole-organ level. Human induced pluripotent stem cell-derived cardiomyocytes as well as ex vivo and in vivo models of IRI were used to t..

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Grants

Awarded by Australian National Heart Foundation


Awarded by National Health and Medical Research Council Development grant


Awarded by American Australian Association


Awarded by Australian National Health & Medical Research Council


Awarded by The Medical Research Future Fund


Awarded by Australian Research Council


Funding Acknowledgements

Financial support was provided by The University of Queensland Strategic Funding Research Initiatives (to Drs Palpant, King, Fraser, Hudson, Porrello, Reichelt, and Thomas), the Australian National Heart Foundation (grants 101889 to Dr Palpant and 199385 to Dr White), National Health and Medical Research Council Development grant (grant 2000178 to Drs Palpant, King, Macdonald, and Fraser), a UniQuest Pathfinder Award (Dr Palpant), the Whitaker International Program (scholar grant to Dr Redd), the American Australian Association (grant 441 to Dr Redd), the St Vincent's Clinic Foundation (to Dr Macdonald), the Australian National Health & Medical Research Council (program grant 1074386 to Dr Macdonald, project grant APP1085996 to Dr Thomas, and Principal Research Fellowship APP1136889 and development grant APP1158521 to Dr King), The Medical Research Future Fund (grant APP2007625 to Drs Palpant and King), and the Australian Research Council (Discovery Early Career Researcher Award DE180100976 to Dr Cuellar-Partida).