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

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.

Automated summary

This study investigated the role of TNF-related apoptosis-inducing ligand (TRAIL) in initiating apoptosis by binding to death receptor 5 (DR5) in rats after acute myocardial infarction (AMI), and found that soluble DR5 (sDR5) inhibited this process. Treatment with sDR5 reduced myocardial infarct size, levels of CK-MB and cTn-I, decreased expression of caspase 3 and PARP, and increased expression of the anti-apoptotic factor Bcl-2 in rats after AMI. The expression of DR5 was also down-regulated after sDR5 treatment, suggesting its beneficial effect on the myocardium.