Expression of cardiac function genes in adult stem cells is increased by treatment with nitric oxide agents

Biochem Biophys Res Commun. 2009 Jan 16;378(3):456-61. doi: 10.1016/j.bbrc.2008.11.061. Epub 2008 Nov 24.

Abstract

Mesenchymal stem cells (MSCs) have received special attention for cardiomyoplasty because several studies have shown that they differentiate into cardiomyocytes both in vitro and in vivo. Nitric oxide (NO) is a free radical signaling molecule that regulates several differentiation processes including cardiomyogenesis. Here, we report an investigation of the effects of two NO agents (SNAP and DEA/NO), able to activate both cGMP-dependent and -independent pathways, on the cardiomyogenic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived stem cells (ADSCs). The cells were isolated, cultured and treated with NO agents. Cardiac- and muscle-specific gene expression was analyzed by indirect immunofluorescence, flow cytometry, RT-PCR and real-time PCR. We found that untreated (control) ADSCs and BM-MSCs expressed some muscle markers and NO-derived intermediates induce an increased expression of some cardiac function genes in BM-MSCs and ADSCs. Moreover, NO agents considerably increased the pro-angiogenic potential mostly of BM-MSCs as determined by VEGF mRNA levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Stem Cells / cytology
  • Adult Stem Cells / drug effects*
  • Adult Stem Cells / metabolism
  • Aged
  • Antigens, CD / genetics
  • Cardiomyoplasty
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Connexin 43 / genetics
  • Gene Expression
  • Genetic Markers
  • Heart / physiology
  • Humans
  • Hydrazines / pharmacology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Middle Aged
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism
  • Muscle Proteins / genetics
  • Myocytes, Cardiac / cytology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / pharmacology*
  • Penicillamine / analogs & derivatives*
  • Penicillamine / pharmacology
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Antigens, CD
  • Connexin 43
  • Genetic Markers
  • Hydrazines
  • Muscle Proteins
  • Nitric Oxide Donors
  • S-nitro-N-acetylpenicillamine
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide
  • 1,1-diethyl-2-hydroxy-2-nitrosohydrazine
  • Penicillamine