TRAIL inhibition by soluble death receptor 5 protects against acute myocardial infarction in rats
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Updated: Aug 22, 2025
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Mingli Wang1, Yinxiang Wei1, Xuance Wang1
1Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, School of Medical Sciences, Henan University, Kaifeng, 475004, People's Republic of China.
Abstract:
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.
Insights
Soluble death receptor 5 (sDR5) protects heart cells from death after acute myocardial infarction (AMI). This therapy reduces heart damage by inhibiting apoptosis, offering potential for future AMI treatments.
Area of Science:
- Cardiovascular Research
- Cell Death Mechanisms
- Molecular Biology
Background:
- Acute myocardial infarction (AMI) leads to significant mortality and morbidity.
- Cardiomyocyte apoptosis is a primary driver of cell death following AMI.
- Targeting apoptosis pathways presents a potential therapeutic strategy for AMI.
Purpose of the Study:
- To investigate the role of TNF-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 in AMI.
- To evaluate the therapeutic potential of soluble DR5 (sDR5) in mitigating myocardial damage post-AMI.
- To elucidate the mechanism by which sDR5 affects cardiomyocyte apoptosis.
Main Methods:
- Analysis of TRAIL and DR5 expression in serum and myocardial tissue of AMI patients and rats.
- Administration of sDR5 to rats post-AMI and assessment of therapeutic effects.
- Measurement of myocardial infarct size, cardiac enzyme levels (CK-MB, cTn-I), and apoptosis-related protein expression (caspase 3, PARP, Bcl-2).
Main Results:
- TRAIL was downregulated in AMI patients; TRAIL and DR5 were upregulated in rat myocardium post-AMI.
- sDR5 treatment reduced infarct size and cardiac enzyme levels.
- sDR5 treatment decreased caspase 3 and PARP expression while increasing Bcl-2, indicating reduced apoptosis.
- sDR5 treatment led to downregulation of DR5 expression in the myocardium.
Conclusions:
- sDR5 effectively reduces myocardial damage in a rat model of AMI.
- sDR5 exerts its protective effects by inhibiting cardiomyocyte apoptosis.
- Downregulation of DR5 expression by sDR5 is associated with beneficial outcomes in AMI, suggesting therapeutic potential.
