TRAIL inhibition by soluble death receptor 5 protects against acute myocardial infarction in rats.

Mingli Wang, Yinxiang Wei, Xuance Wang, Fanni Ma, Weina Zhu, Xi Chen, Xiaoming Zhong, Shulian Li, Jun Zhang, Guangchao Liu, Yaohui Wang, Yuanfang Ma

Heart and vessels 2023 Mar

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Acute myocardial infarction (AMI) is associated with high morbidity and mortality. An effective therapeutic strategy is to rescue cardiomyocytes from death. Apoptosis is a key reason of cardiomyocyte death that can be prevented. In this study, we investigated the role of TNF-related apoptosis-inducing ligand (TRAIL) in initiating apoptosis by binding to death receptor 5 (DR5), and this procession is inhibited by soluble DR5 (sDR5) in rats after AMI. First, we found that the level of TRAIL in serum was down-regulated in AMI patients. Then, TRAIL and DR5 expression was analysed in the myocardium of rats after AMI, and their expression was up-regulated. sDR5 treatment reduced the myocardial infarct size and the levels of CK-MB and cTn-I in serum. The expression of caspase 3 and PARP is decreased, but the anti-apoptotic factor Bcl-2 was increased in sDR5 treatment rats after AMI. DR5 expression was also analysed after sDR5 treatment and it was down-regulated, and a low level of DR5 expression seemed to be beneficial for the myocardium. Overall, our findings indicated that sDR5 decreases myocardial damage by inhibiting apoptosis in rat after AMI. We expect to observe the potential therapeutic effects of sDR5 on AMI in the future. © 2022. Springer Japan KK, part of Springer Nature.

Citation

Mingli Wang, Yinxiang Wei, Xuance Wang, Fanni Ma, Weina Zhu, Xi Chen, Xiaoming Zhong, Shulian Li, Jun Zhang, Guangchao Liu, Yaohui Wang, Yuanfang Ma. TRAIL inhibition by soluble death receptor 5 protects against acute myocardial infarction in rats. Heart and vessels. 2023 Mar;38(3):448-458