The Effect of Angiotensin II, Retinoic Acid, EGCG, and Vitamin C on the Cardiomyogenic Differentiation Induction of Human Amniotic Fluid-Derived Mesenchymal Stem Cells

Human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) may be potentially applied in cell therapy or regenerative medicine as a new alternative source of stem cells. They could be particularly valuable in restoring cardiac tissue after myocardial infarction or other cardiovascular diseases. We investigated the potential of biologically active compounds, namely, angiotensin II, retinoic acid (RA), epigallocatechin-3-gallate (EGCG), vitamin C alone, and the combinations of RA, EGCG, and vitamin C with angiotensin II to induce cardiomyogenic differentiation of AF-MSCs. We observed that the upregulated expression of cardiac gene markers (NKX2-5, MYH6, TNNT2, and DES) and cardiac ion channel genes (sodium, calcium, the potassium) also the increased levels of Connexin 43 and Nkx2.5 proteins. Extracellular flux analysis, applied for the first time on AF-MSCs induced with biologically active compounds, revealed the switch in AF-MSCS energetic phenotype and enhanced utilization of oxidative phosphorylation for energy production. Moreover, we demonstrated changes in epigenetic marks associated with transcriptionally active (H3K4me3, H3K9ac, and H4hyperAc) or repressed (H3K27me3) chromatin. All in all, we demonstrated that explored biomolecules were able to induce alterations in AF-MSCs at the phenotypic, genetic, protein, metabolic, and epigenetic levels, leading to the formation of cardiomyocyte progenitors that may become functional heart cells in vitro or in vivo.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:21

Enthalten in:

International journal of molecular sciences - 21(2020), 22 vom: 19. Nov.

Sprache:

Englisch

Beteiligte Personen:

Gasiūnienė, Monika [VerfasserIn]
Valatkaitė, Elvina [VerfasserIn]
Navakauskaitė, Aistė [VerfasserIn]
Navakauskienė, Rūta [VerfasserIn]

Links:

Volltext

Themen:

11128-99-7
5688UTC01R
8R1V1STN48
Amniotic fluid
Angiotensin II
Ascorbic Acid
BQM438CTEL
Calcium Channels
Cardiac
Cardiac Myosins
Catechin
Chromatin
Connexin 43
Differentiation
EC 3.6.1.-
EC 3.6.4.1
Epigallocatechin gallate
GJA1 protein, human
Histones
Homeobox Protein Nkx-2.5
Journal Article
MYH6 protein, human
Metabolism
Myosin Heavy Chains
NKX2-5 protein, human
PQ6CK8PD0R
Potassium Channels
Stem cells
TNNT2 protein, human
Tretinoin
Troponin T

Anmerkungen:

Date Completed 04.03.2021

Date Revised 06.01.2023

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms21228752

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317951289