Histone deacetylases in myocardial infarction: Orchestrating programmed cell death pathways and emerging therapeutic...

Area of Science:

• Cardiovascular Biology
• Epigenetics
• Cell Death Research

Background:

• Myocardial infarction (MI) causes irreversible cardiomyocyte loss via multiple programmed cell death (PCD) pathways.
• Histone deacetylases (HDACs) are key epigenetic regulators influencing PCD, inflammation, and cardiac remodeling post-MI.
• HDAC isoforms have complex, context-dependent roles in promoting or suppressing cardiomyocyte death.

Purpose of the Study:

• To systematically review recent advances on isoform-specific HDAC roles in regulating distinct PCD pathways during MI.
• To highlight the mechanistic complexity and therapeutic potential of HDACs in myocardial injury.
• To critically evaluate emerging preclinical strategies targeting HDACs for MI treatment.

Main Methods:

• Systematic literature review of preclinical and clinical studies.
• Analysis of molecular mechanisms linking HDACs to specific PCD pathways (apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis).
• Evaluation of therapeutic interventions targeting HDACs, including inhibitors and activators.

Main Results:

• HDACs modulate acetylation of histones and non-histone proteins, impacting cardiomyocyte survival and death.
• Isoform-specific HDACs differentially regulate various PCD pathways, influencing myocardial injury and inflammation.
• Preclinical studies show promise for HDAC inhibitors and activators in preserving cardiac function post-MI.

Conclusions:

• Deciphering isoform-specific HDAC-mediated regulation of cardiomyocyte PCD is crucial for understanding MI.
• Targeting specific HDACs presents promising therapeutic avenues for preserving myocardial integrity and improving outcomes after MI.
• Further research into translational prospects of HDAC-targeted therapies is warranted for clinical application.