Therapeutic effects of histone deacetylase inhibitors on heart disease

Area of Science:

• Cardiovascular Science
• Molecular Biology
• Pharmacology

Background:

• Aberrant histone deacetylase (HDAC) activity and expression are linked to cardiovascular disease pathogenesis.
• Numerous preclinical studies indicate cardioprotective effects of various HDAC inhibitors.
• Understanding HDAC inhibitor mechanisms is crucial for developing effective, low-toxicity therapies.

Purpose of the Study:

• To review the preclinical effects of HDAC inhibitors targeting Zn2+-dependent HDACs.
• To elucidate the underlying mechanisms of HDAC inhibitor-mediated cardioprotection.
• To highlight therapeutic potential in various cardiac conditions.

Main Methods:

• Review of preclinical studies on HDAC inhibitors and cardiac diseases.
• Analysis of mechanisms including suppression of fibrosis and fetal gene expression.
• Examination of effects on angiogenesis, mitochondrial biogenesis, and electrical remodeling.

Main Results:

• HDAC inhibitors demonstrate protective effects against cardiac hypertrophy, hypertension, myocardial infarction, heart failure, and atrial fibrillation.
• Mechanisms include suppression of cardiac fibrosis and fetal gene expression.
• Enhanced angiogenesis, mitochondrial biogenesis, and regulated apoptosis, autophagy, and cell cycle arrest contribute to cardioprotection.

Conclusions:

• HDAC inhibitors targeting Zn2+-dependent enzymes offer significant preclinical cardioprotective potential.
• Diverse mechanisms underlie their efficacy against various cardiac pathologies.
• Further research into isoform-selective inhibitors is warranted for clinical translation.