ATPase inhibitory factor 1 protects the heart from acute myocardial ischemia/reperfusion injury through activating AMPK signaling pathway

Wu, Jia-Wei; Hu, Hao; Hua, Jin-sheng; Ma, Li-Kun

doi:10.7150/ijbs.64956

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Int J Biol Sci 2022; 18(2):731-741. doi:10.7150/ijbs.64956 This issue Cite

Research Paper

ATPase inhibitory factor 1 protects the heart from acute myocardial ischemia/reperfusion injury through activating AMPK signaling pathway

Jia-Wei Wu, Hao Hu, Jin-sheng Hua, Li-Kun Ma^✉

Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, 230001, China

Citation:

Wu JW, Hu H, Hua Js, Ma LK. ATPase inhibitory factor 1 protects the heart from acute myocardial ischemia/reperfusion injury through activating AMPK signaling pathway. Int J Biol Sci 2022; 18(2):731-741. doi:10.7150/ijbs.64956. https://www.ijbs.com/v18p0731.htm

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Abstract

Rationale: Myocardial ischemia/reperfusion (I/R) injury is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction (AMI). The mitochondrial F1Fo-ATPase inhibitory factor 1 (IF1) blocks the reversal of the F1Fo-ATP synthase to prevent detrimental consumption of cellular ATP and associated demise. In the present study, we study the role and mechanism of IF1 in myocardial I/R injury.

Methods: Mice were ligated the left anterior descending coronary artery to build the I/R model in vivo. Rat hearts were isolated and perfused with constant pressure according to Langendorff. Also, neonatal cardiomyocytes hypoxia-reoxygenation (H/R) model was also used. Myocardial infarction area, cardiac function, cellular function, and cell viability was conducted and compared.

Results: Our data revealed that IF1 is upregulated in hearts after I/R and cardiomyocytes with hypoxia/re-oxygenation (H/R). IF1 delivered with adenovirus and adeno-associated virus serotype 9 (AAV9) ameliorated cardiac dysfunction and pathological development induced by I/R ex vivo and in vivo. Mechanistically, IF1 stimulates glucose uptake and glycolysis activity and stimulates AMPK activation during in vivo basal and I/R and in vitro OGD/R conditions, and activation of AMPK by IF1 is responsible for its cardioprotective effects against H/R-induced injury.

Conclusions: These results suggest that increased IF1 in the I/R heart confer cardioprotective effects via activating AMPK signaling. Therefore, IF1 can be used as a potential therapeutic target for the treatment of pathological ischemic injury and heart failure.

Keywords: ATPase inhibitory factor 1, ischemia/reperfusion injury, heart, AMPK

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APA

Wu, J.W., Hu, H., Hua, J.s., Ma, L.K. (2022). ATPase inhibitory factor 1 protects the heart from acute myocardial ischemia/reperfusion injury through activating AMPK signaling pathway. International Journal of Biological Sciences, 18(2), 731-741. https://doi.org/10.7150/ijbs.64956.

ACS

Wu, J.W.; Hu, H.; Hua, J.s.; Ma, L.K. ATPase inhibitory factor 1 protects the heart from acute myocardial ischemia/reperfusion injury through activating AMPK signaling pathway. Int. J. Biol. Sci. 2022, 18 (2), 731-741. DOI: 10.7150/ijbs.64956.

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CSE

Wu JW, Hu H, Hua Js, Ma LK. 2022. ATPase inhibitory factor 1 protects the heart from acute myocardial ischemia/reperfusion injury through activating AMPK signaling pathway. Int J Biol Sci. 18(2):731-741.

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