Int J Med Sci 2020; 17(16):2454-2467. doi:10.7150/ijms.47598

Research Paper

An α2-adrenoceptor agonist: Dexmedetomidine induces protective cardiomyocyte hypertrophy through mitochondrial-AMPK pathway

Xiaojian Weng1*, Hua Liu2*, Xiaodan Zhang3, Qianqian Sun1, Cheng Li1, Minglu Gu1, Yanyifang Xu1, Shitong Li4, Weiwei Li1✉, Jianer Du1✉

1. Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai, China.
2. Department of Anesthesiology, The Ninth People's Hospital, Shanghai, China.
3. Department of ICU, Shanghai General Hospital, Shanghai, China.
4. Department of Anesthesiology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
*These authors contributed equally to this work.

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Citation:
Weng X, Liu H, Zhang X, Sun Q, Li C, Gu M, Xu Y, Li S, Li W, Du J. An α2-adrenoceptor agonist: Dexmedetomidine induces protective cardiomyocyte hypertrophy through mitochondrial-AMPK pathway. Int J Med Sci 2020; 17(16):2454-2467. doi:10.7150/ijms.47598. Available from http://www.medsci.org/v17p2454.htm

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Abstract

Aims: Dexmedetomidine (Dex) as a highly selective α2-adrenoceptor agonist, was widely used anesthetic in perioperative settings, whether Dex induces cardiac hypertrophy during perioperative administration is unknown.

Methods: The effects of Dex on cardiac hypertrophy were explored using the transverse aortic constriction model and neonatal rat cardiomyocytes.

Results: We reported that Dex induces cardiomyocyte hypertrophy with activated ERK, AKT, PKC and inactivated AMPK in both wild-type mice and primary cultured rat cardiomyocytes. Additionally, pre-administration of Dex protects against transverse aortic constriction induced-heart failure in mice. We found that Dex up-regulates the activation of ERK, AKT, and PKC via suppression of AMPK activation in rat cardiomyocytes. However, suppression of mitochondrial coupling efficiency and membrane potential by FCCP blocks Dex induced AMPK inactivation as well as ERK, AKT, and PKC activation. All of these effects are blocked by the α2-adrenoceptor antagonist atipamezole.

Conclusion: The present study demonstrates Dex preconditioning induces cardiac hypertrophy that protects against heart failure through mitochondria-AMPK pathway in perioperative settings.

Keywords: anesthesia, cardiac preconditioning, dexmedetomidine, cardiac hypertrophy, heart failure, mitochondria