Inhibition of histone deacetylases (HDACs) by trichostatin A (TSA) has previously been shown to induce a pharmacological preconditioning effect against acute myocardial ischemia and reperfusion injury; however, it is not clear whether the mechanism of TSA promotes endogenous angiomyogenesis in infarcted mouse hearts. In the present study, Zhang et al. investigated whether in vivo inhibition of HDAC preserves cardiac performance and prevents cardiac remodeling in mouse myocardial infarction (MI) through stimulation of endogenous regeneration. These studies demonstrate that in vivo inhibition of HDAC improved cardiac functional recovery and antagonized myocardial remodeling in chronic MI. Notably, HDAC inhibition significantly improved animal survival rate after MI, which is associated with the mitigation of both myocardial and serum tumor necrosis factor α levels in MI heart. HDAC inhibition stimulated the self-renewal of cardiac stem cells and resulted in robust increases in proliferation and cytokinesis in the MI hearts, which are associated with the enhancement of the newly formed myocytes and angiogenic responses. HDAC inhibition-induced cardioprotection also involves the activation of Akt-1 and inhibition of apoptosis. This study provides novel evidence that a new therapeutic strategy could be developed based upon HDAC inhibition, eliciting the stimulation of cardiac endogenous regeneration and angiogenesis in the infarcted heart.
See article at J Pharmacol Exp Ther 2012, 341:285–293.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics