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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1453647

(Pro)renin receptor aggravates myocardial pyroptosis in diabetic cardiomyopathy through AMPK-NLRP3 pathway

Provisionally accepted
Shengnan Li Shengnan Li 1Haipeng Jie Haipeng Jie 1Jingjing Zhang Jingjing Zhang 1Yuewen Zhao Yuewen Zhao 2Li Kang Li Kang 3Bo Dong Bo Dong 1,2,4*
  • 1 Department of Pediatric Cardiology, Shandong Provincial Hospital, Jinan, China
  • 2 Department of Cardiology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
  • 3 Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom
  • 4 Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China

The final, formatted version of the article will be published soon.

    As one of the most common complications of diabetes, diabetic cardiomyopathy (DCM) is the main cause of heart failure in patients with diabetes. (Pro) renin receptor (PRR) is a member of renin angiotensin aldosterone system (RAAS). Its activation can not only promote the production of angiotensin I, but also trigger many intracellular signaling pathways independent of Ang Ⅱ. Previous studies have shown that PRR can participate in a variety of disease processes. The purpose of this study was to investigate whether PRR is involved in diabetic myocardial pyroptosis mediated by NLRP3 inflammasome. We established diabetic rats model by intraperitoneal injection of streptozotocin (STZ). Primary cardiomyocytes were stimulated with high glucose and PRR overexpression or PRR knockdown was achieved by adenovirus transfection. We found that overexpression of PRR could stimulate the activation of NLRP3 inflammasome, aggravate diabetic myocardial pyroptosis, and aggravate cardiac dysfunction in DCM. On the contrary, PRR knockdown can alleviate the level of myocardial pyroptosis in DCM and improve cardiac function. The related mechanism was that PRR could inhibit AMPK phosphorylation and promote the activation of NLRP3 inflammasome. In conclusion, the overexpression of PRR may aggravate myocardial pyroptosis in DCM through AMPK-NLRP3 pathway.

    Keywords: pro renin receptor, Diabetic cardiomyopathy, pyroptosis, NLRP3, AMPK (AMP-Activated Protein Kinase)

    Received: 23 Jun 2024; Accepted: 21 Oct 2024.

    Copyright: © 2024 Li, Jie, Zhang, Zhao, Kang and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Bo Dong, Department of Pediatric Cardiology, Shandong Provincial Hospital, Jinan, China

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