Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Improves Energetic Status and Cardiomyogenic Differentiation of Human Dilated Myocardium-Derived Primary Mesenchymal Cells.
Actins
/ metabolism
Adenosine Triphosphate
/ metabolism
Cell Differentiation
/ drug effects
Cell Proliferation
/ drug effects
Cells, Cultured
Histone Deacetylase Inhibitors
/ pharmacology
Histone Deacetylases
/ metabolism
Homeobox Protein Nkx-2.5
/ metabolism
Humans
Membrane Potential, Mitochondrial
/ drug effects
Mesenchymal Stem Cells
/ drug effects
Mitochondria
/ drug effects
Myocytes, Cardiac
/ drug effects
Troponin T
/ metabolism
Vorinostat
/ pharmacology
cardiomyogenic differentiation
dilated cardiomyopathy
histone deacetylase inhibitors
primary mesenchymal cells
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
08 Jul 2020
08 Jul 2020
Historique:
received:
29
05
2020
revised:
03
07
2020
accepted:
05
07
2020
entrez:
12
7
2020
pubmed:
12
7
2020
medline:
17
2
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 32650632
pii: ijms21144845
doi: 10.3390/ijms21144845
pmc: PMC7402340
pii:
doi:
Substances chimiques
Actins
0
Histone Deacetylase Inhibitors
0
Homeobox Protein Nkx-2.5
0
Troponin T
0
Vorinostat
58IFB293JI
Adenosine Triphosphate
8L70Q75FXE
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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