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Updated: Jan 24, 2026
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
A novel therapeutic peptide targeting myocardial reperfusion injury
Prisca Boisguérin1,2, Aurélie Covinhes3,4, Laura Gallot3,4
1CRBM, Univ. Montpellier, CNRS, F-34293 Montpellier, France.
Aims:
Regulated cell death is a main contributor of myocardial ischaemia-reperfusion (IR) injury during acute myocardial infarction. In this context, targeting apoptosis could be a potent therapeutical strategy. In a previous study, we showed that DAXX (death-associated protein) was essential for transducing the FAS-dependent apoptotic signal during IR injury. The present study aims at evaluating the cardioprotective effects of a synthetic peptide inhibiting FAS:DAXX interaction.
Methods And Results:
An interfering peptide was engineered and then coupled to the Tat cell penetrating peptide (Tat-DAXXp). Its internalization and anti-apoptotic properties were demonstrated in primary cardiomyocytes. Importantly, an intravenous bolus injection of Tat-DAXXp (1 mg/kg) 5 min before reperfusion in a murine myocardial IR model decreased infarct size by 48% after 24 h of reperfusion. In addition, Tat-DAXXp was still efficient after a 30-min delayed administration, and was completely degraded and eliminated within 24 h thereby reducing risks of potential side effects. Importantly, Tat-DAXXp reduced mouse early post-infarction mortality by 67%. Mechanistically, cardioprotection was supported by both anti-apoptotic and pro-survival effects, and an improvement of myocardial functional recovery as evidenced in ex vivo experiments.
Conclusions:
Our study demonstrates that a single dose of Tat-DAXXp injected intravenously at the onset of reperfusion leads to a strong cardioprotection in vivo by inhibiting IR injury validating Tat-DAXXp as a promising candidate for therapeutic application.
Insights
A novel peptide, Tat-DAXXp, effectively reduces heart damage after myocardial infarction by inhibiting apoptosis. This peptide shows promise for treating ischemia-reperfusion injury with reduced side effects.
Area of Science:
- Cardiovascular Research
- Cell Death Mechanisms
- Molecular Cardiology
Background:
- Regulated cell death, particularly apoptosis, significantly contributes to myocardial ischemia-reperfusion (IR) injury during acute myocardial infarction.
- Targeting apoptosis presents a potential therapeutic strategy for mitigating IR injury.
- Death-associated protein (DAXX) plays a crucial role in transducing the FAS-dependent apoptotic signal in IR injury.
Purpose of the Study:
- To evaluate the cardioprotective effects of a synthetic peptide designed to inhibit the FAS:DAXX interaction.
- To assess the therapeutic potential of targeting the FAS:DAXX pathway in myocardial IR injury.
Main Methods:
- Engineered a synthetic peptide (Tat-DAXXp) by coupling an interfering peptide with the Tat cell-penetrating peptide.
- Demonstrated Tat-DAXXp internalization and anti-apoptotic properties in primary cardiomyocytes.
- Administered Tat-DAXXp intravenously in a murine myocardial IR model to assess infarct size, mortality, and functional recovery.
Main Results:
- Tat-DAXXp significantly decreased infarct size by 48% in a murine myocardial IR model.
- The peptide remained effective even with delayed administration (30 min) and was rapidly degraded within 24 hours.
- Tat-DAXXp reduced early post-infarction mortality by 67% and improved myocardial functional recovery.
Conclusions:
- A single intravenous dose of Tat-DAXXp at reperfusion onset provides robust cardioprotection by inhibiting IR injury.
- Tat-DAXXp demonstrates significant therapeutic potential for treating myocardial IR injury.
- The mechanism involves both anti-apoptotic and pro-survival effects, alongside improved cardiac function.
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