2. Academic Validation
  3. Vaspin alleviates myocardial ischaemia/reperfusion injury via activating autophagic flux and restoring lysosomal function

Vaspin alleviates myocardial ischaemia/reperfusion injury via activating autophagic flux and restoring lysosomal function

  • Biochem Biophys Res Commun. 2018 Sep 5;503(2):501-507. doi: 10.1016/j.bbrc.2018.05.004.
Feihong Yang 1,  Li Xue 1,  Ziqi Han 1,  Feng Xu 1,  Shengchuan Cao 1,  Shuai Dai 1,  Baoshan Liu 1,  Qiuhuan Yuan 1,  Zheng Wang 1,  Ping Guo 2,  Yuguo Chen 3
Affiliations

Affiliations

  • 1 Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Medical Insurance Office, Qilu Hospital of Shandong University, Jinan, China. Electronic address: 13953100732@163.com.
  • 3 Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address: chen919085@sdu.edu.cn.
PMID: 29730286 DOI: 10.1016/j.bbrc.2018.05.004
Abstract

Visceral adipose tissue-derived Serine Protease Inhibitor (Vaspin), as a secretory adipokine, was reported to exert a protective role on Insulin resistance. Recent studies showed that serum Vaspin level was downregulated in patients with coronary artery disease. However, whether Vaspin exerted specific effects on myocardial injury remains unknown. In this study, we determined to explore the role of Vaspin overexpression in myocardial ischaemia/reperfusion (I/R) injury and the underlying mechanisms. Our results showed that the systemic delivery of adeno-associated virus-vaspin to mice reduced myocardial infarct size and Apoptosis, and improved cardiac function after reperfusion, accompanied with upregulated autophagic flux and restored lysosomal function in the ischaemic heart. Blockage of the autophagic flux with choroquine mitigated the protection of Vaspin on myocardial I/R injury. Moreover, we testified that administration of exogenous recombinant human Vaspin on cultured cardiomyocytes suppressed hypoxia/reoxygenation-induced Apoptosis, through the AMPK-mTOR-upregulated autophagic flux. Overall, we verified that Vaspin functions as an adipokine which can alleviate I/R injury in the heart by suppressing myocardial Apoptosis through AMPK-mTOR-dependent activation of autophagic flux, and then provided a potential breakthrough in the treatment of myocardial I/R injury and other ischaemic diseases.

Keywords

AMPK; Autophagic flux; Cardiomyocytes; Myocardial ischaemia/reperfusion injury; Vaspin.

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