Histone acetyltransferase 1 promotes postinfarction inflammatory response by regulation of monocyte histone succinylation.

Summary

This mechanistic study identifies histone acetyltransferase 1 (Hat1) as a functional succinyltransferase that drives histone H3K23 succinylation in monocytes, amplifying proinflammatory gene programs after myocardial infarction. Genetic Hat1 deficiency improved cardiac function, decreased infarct size, and dampened inflammatory responses in mouse MI, implicating an epigenetic axis as a therapeutic target.

Key Findings

• Histone H3K23 succinylation is markedly upregulated in monocytes from MI patients and mouse models and correlates with heightened inflammatory responses.
• Hat1 acts as a succinyltransferase; its expression increases in proinflammatory monocytes and recruits H3K23 succinylation to proinflammatory gene loci.
• Hat1 deficiency improves cardiac function, reduces infarct size, and suppresses inflammatory responses post-MI in mice.

Clinical Implications

While preclinical, targeting Hat1 or histone succinylation could modulate maladaptive post-MI inflammation, complementing current anti-inflammatory or cardioprotective strategies.

Limitations

• Translational gap: no pharmacologic Hat1 inhibitors tested in vivo
• Cell-type specificity beyond monocytes/macrophages not fully delineated

Future Directions

Develop selective Hat1 modulators; define temporal windows for succinylation targeting post-MI; map cell-type–specific succinylomes and test combinatorial therapy with guideline-directed care.