Int J Biol Sci 2022; 18(2):858-872. doi:10.7150/ijbs.67724 This issue

Research Paper

Propionate alleviates myocardial ischemia-reperfusion injury aggravated by Angiotensin II dependent on caveolin-1/ACE2 axis through GPR41

Fan Deng1,2,3*, Liang-Qing Zhang3*, Han Wu4*, Yu Chen1, Wen-Qian Yu5, Rong-Hui Han3, Yuan Han6, Xiao-Qi Zhang7, Qi-Shun Sun1, Ze-Bin Lin1, Yu Wang2, Yong-Pan Liu2, Jing-Yi Chen2✉, Ke-Xuan Liu1✉, Jing-Juan Hu1✉

1. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
2. Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.
3. Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
4. Department of Dermatology, Shunde Hospital, Southern Medical University, Foshan, China.
5. The First Ward of Pain Department, Hubei NO. 3 People's Hospital of Jianghan University, Wuhan 430000, China.
6. Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
7. Major of Clinical Medicine, Nanshan College, Guangzhou Medical University, Guangzhou 510515, China.
* These authors contributed equally to this study

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Deng F, Zhang LQ, Wu H, Chen Y, Yu WQ, Han RH, Han Y, Zhang XQ, Sun QS, Lin ZB, Wang Y, Liu YP, Chen JY, Liu KX, Hu JJ. Propionate alleviates myocardial ischemia-reperfusion injury aggravated by Angiotensin II dependent on caveolin-1/ACE2 axis through GPR41. Int J Biol Sci 2022; 18(2):858-872. doi:10.7150/ijbs.67724. Available from https://www.ijbs.com/v18p0858.htm

File import instruction

Abstract

Graphic abstract

Myocardial ischemia/reperfusion (I/R) injury is still a lack of effective therapeutic drugs, and its molecular mechanism is urgently needed. Studies have shown that the intestinal flora plays an important regulatory role in cardiovascular injury, but the specific mechanism has not been fully elucidated. In this study, we found that an increase in Ang II in plasma was accompanied by an increase in the levels of myocardial injury during myocardial reperfusion in patients with cardiopulmonary bypass. Furthermore, Ang II treatment enhanced mice myocardial I/R injury, which was reversed by caveolin-1 (CAV-1)-shRNA or strengthened by angiotensin-converting enzyme 2 (ACE2)-shRNA. The results showed that CAV-1 and ACE2 have protein interactions and inhibit each other's expression. In addition, propionate, a bacterial metabolite, inhibited the elevation of Ang II and myocardial injury, while GPR41-shRNA abolished the protective effects of propionate on myocardial I/R injury. Clinically, the propionate content in the patient's preoperative stool was related to Ang II levels and myocardial I/R injury levels during myocardial reperfusion. Taken together, propionate alleviates myocardial I/R injury aggravated by Ang II dependent on CAV-1/ACE2 axis through GPR41, which provides a new direction that diet to regulate the intestinal flora for treatment of myocardial I/R injury.

Keywords: Myocardial ischemia reperfusion, Angiotensin II, Caveolin-1, Angiotensin-converting enzyme 2, Propionate, G-protein coupled receptor 41.