Suberoylanilide hydroxamic acid (SAHA) improved the energetic status of mitochondria and increased the expression of cardiac-specific proteins in dilated myocardium-isolated mesenchymal stromal cells.
Does the HDAC inhibitor SAHA improve energetic status and cardiomyogenic differentiation in human dilated myocardium-derived mesenchymal stromal cells?
The HDAC inhibitor SAHA improves the energetic status and cardiomyogenic differentiation of mesenchymal stromal cells derived from human dilated myocardium, suggesting a potential regenerative therapeutic approach for dilated cardiomyopathy.
BACKGROUND: In this study the effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) on the energetic status and cardiomyogenic differentiation of human healthy and dilated myocardium-derived mesenchymal stromal cells (hmMSC) have been investigated. METHODS: The hmMSC were isolated from the healthy and dilated post-operation heart biopsies by explant outgrowth method. Cell proliferation, HDAC activity, mitochondrial membrane potential, and level of adenosine triphosphate (ATP) were evaluated. The effect of SAHA on mitochondrial parameters has been investigated also by Seahorse XF analyzer and cardiomyogenic differentiation was confirmed by the expression of transcription factor NK2 Homeobox 5 (Nkx2.5), cardiac troponin T and alpha cardiac actin at gene and protein levels. RESULTS: Dilated myocardium-derived hmMSC had almost 1.5 folds higher HDAC activity compared to the healthy cells and significantly lower mitochondrial membrane potential and ATP level. HDAC class I and II inhibitor SAHA improved energetic status of mitochondria in dilated myocardium-isolated hmMSC and increased expression of cardiac specific proteins during 14 days of exposure of cells to SAHA. CONCLUSIONS: HDAC inhibitor SAHA can be a promising therapeutic for dilated cardiomyopathy (DCM). Dilated hmMSC exposed to SAHA improved energetic status and, subsequently, cardiomyogenic differentiation. Data suggest that human dilated myocardium-derived MSC still have cardio tissue regenerative potential, which might be stimulated by HDAC inhibitors.
Mikšiūnas et al. (Wed,) conducted a other in Dilated cardiomyopathy. Suberoylanilide hydroxamic acid (SAHA) vs. Healthy cells / untreated cells was evaluated on Energetic status (mitochondrial membrane potential, ATP level) and cardiomyogenic differentiation. Suberoylanilide hydroxamic acid (SAHA) improved the energetic status of mitochondria and increased the expression of cardiac-specific proteins in dilated myocardium-isolated mesenchymal stromal cells.