Pharmacological inhibition of acid sensing ion channel 1a protects the heart from ischemia-reperfusion injury

Redd, M.; Scheuer, S.; Saez, N.; Gao, L.; Hicks, M.; Villanueva, J.; Reichelt, M.; Peart, J.; See Hoe, L.; Chiu, H.; Chen, X.; Sun, Y.; Suen, J.; Maljevic, S.; Thomas, W.; Cuellar-Partida, G.; Fraser, J.; Petrou, S.; King, G.; MacDonald, P.; Palpant, N.

doi:10.1101/869826

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bioRxiv · 10.1101/869826

Pharmacological inhibition of acid sensing ion channel 1a protects the heart from ischemia-reperfusion injury

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Abstract

The proton-gated acid-sensing ion channel 1a (ASIC1a) is implicated in the injury response to cerebral ischemia but little is known about its role in cardiac ischemia. We provide genetic evidence that ASIC1a is involved in myocardial ischemia-reperfusion injury (IRI) and show that pharmacological inhibition of ASIC1a yields robust cardioprotection in rodent and human models of cardiac ischemia, resulting in improved post-IRI cardiac viability and function. Consistent with a key role for ASIC1a in cardiac ischemia, we show that polymorphisms in the ASIC1 genetic locus are strongly associated with myocardial infarction. Collectively, our data provide compelling evidence that ASIC1a is a key target for cardioprotective drugs to reduce the burden of disease associated with myocardial ischemia.

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Redd, M., Scheuer, S., Saez, N., Gao, L., Hicks, M., Villanueva, J., Reichelt, M., Peart, J., See Hoe, L., Chiu, H., Chen, X., Sun, Y., Suen, J., Maljevic, S., Thomas, W., Cuellar-Partida, G., Fraser, J., Petrou, S., King, G., MacDonald, P., Palpant, N.. 2019-12-10. Pharmacological inhibition of acid sensing ion channel 1a protects the heart from ischemia-reperfusion injury. https://doi.org/10.1101/869826

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