Pyroptosis inhibition improves the symptom of acute myocardial infarction

Cell Death and Disease, 2021 · DOI: https://doi.org/10.1038/s41419-021-04143-3 · Published: September 3, 2021

Cardiovascular Science Immunology Genetics

Simple Explanation

Acute myocardial infarction (AMI) is a leading cause of mortality, and early intervention is crucial. The study investigates molecular features in the early stages of AMI using a mouse model. The research found that the immune system and pyroptosis, a form of programmed cell death, are activated during AMI. Inhibiting pyroptosis with VX-765 reduced heart damage in mice. WIPI1, a protein highly expressed in the heart, was identified as a potential early diagnostic biomarker for AMI, with increased expression in AMI patients' blood.

Study Duration

72 hours

Participants

Thirty male C57BL/6 mice (8 weeks old) and peripheral blood cells of patients with early-stage AMI

Evidence Level

Not specified

Key Findings

1
Immune system activation and subsequent pyroptosis occur in the early stages (6-24 hours) of AMI in a mouse model.
2
Inhibition of pyroptosis with VX-765 significantly reduces infarct size and improves cardiomyocyte function in mice.
3
WIPI1 is significantly upregulated early (1 hour) after AMI and shows promise as a potential early diagnostic biomarker, also is signiﬁcantly higher in the peripheral blood of patients with AMI than healthy control.

Research Summary

This study profiles transcriptomes and proteomes in a mouse model of AMI, revealing early immune system activation and pyroptosis. VX-765, a pyroptosis inhibitor, reduced infarct size and improved heart function, suggesting it as a potential therapeutic target. WIPI1 was identified as a potential early diagnostic biomarker for AMI, showing increased expression in both mouse models and human patients.

Practical Implications

Early Diagnosis

WIPI1 could be used as an early diagnostic biomarker for AMI, allowing for faster intervention.

Therapeutic Intervention

Pyroptosis inhibitors, such as VX-765, may serve as a pre-treatment to reduce heart damage during AMI.

Prolonging Optimal Cure Time

VX-765 before clinical treatment could extend the optimal time of clinical outcome.

Study Limitations

1
The study is primarily based on a mouse model, requiring validation in human clinical trials.
2
Further research is needed to fully elucidate the regulatory mechanisms of pyroptosis during AMI.
3
Clinical trials is necessary to determine whether the findings can translate to application.

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