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Open AccessArticle

Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Improves Energetic Status and Cardiomyogenic Differentiation of Human Dilated Myocardium-Derived Primary Mesenchymal Cells

1
Department of Regenerative medicine, State Research Institute Centre for Innovative Medicine, LT 08406 Vilnius, Lithuania
2
Centre of Cardiothoracic Surgery of Vilnius University Hospital Santariskiu Clinic, LT 08406 Vilnius, Lithuania
3
Department of Integrative Pathophysiology, Universitätsmedizin Mannheim, Maybachstr. 14, 68169 Mannheim, Germany
4
Myomedix Ltd., Im Biengarten 36, 69151 Neckargemuend, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(14), 4845; https://doi.org/10.3390/ijms21144845
Received: 29 May 2020 / Revised: 3 July 2020 / Accepted: 5 July 2020 / Published: 8 July 2020
(This article belongs to the Special Issue Cell Programming for Cardiovascular Disease Modeling and Therapy)
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. View Full-Text
Keywords: histone deacetylase inhibitors; dilated cardiomyopathy; cardiomyogenic differentiation; primary mesenchymal cells histone deacetylase inhibitors; dilated cardiomyopathy; cardiomyogenic differentiation; primary mesenchymal cells
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MDPI and ACS Style

Miksiunas, R.; Rucinskas, K.; Janusauskas, V.; Labeit, S.; Bironaite, D. Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Improves Energetic Status and Cardiomyogenic Differentiation of Human Dilated Myocardium-Derived Primary Mesenchymal Cells. Int. J. Mol. Sci. 2020, 21, 4845. https://doi.org/10.3390/ijms21144845

AMA Style

Miksiunas R, Rucinskas K, Janusauskas V, Labeit S, Bironaite D. Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Improves Energetic Status and Cardiomyogenic Differentiation of Human Dilated Myocardium-Derived Primary Mesenchymal Cells. International Journal of Molecular Sciences. 2020; 21(14):4845. https://doi.org/10.3390/ijms21144845

Chicago/Turabian Style

Miksiunas, Rokas; Rucinskas, Kestutis; Janusauskas, Vilius; Labeit, Siegfried; Bironaite, Daiva. 2020. "Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Improves Energetic Status and Cardiomyogenic Differentiation of Human Dilated Myocardium-Derived Primary Mesenchymal Cells" Int. J. Mol. Sci. 21, no. 14: 4845. https://doi.org/10.3390/ijms21144845

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