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