Expression of cardiac function genes in adult stem cells is increased by treatment with nitric oxide agents.
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.
Rebelatto
Carmen K
CK
Núcleo de Cardiomioplastia Celular, Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, Brazil.
Aguiar
Alessandra M
AM
Senegaglia
Alexandra C
AC
Aita
Carlos M
CM
Hansen
Paula
P
Barchiki
Fabiane
F
Kuligovski
Crisciele
C
Olandoski
Márcia
M
Moutinho
José A
JA
Dallagiovanna
Bruno
B
Goldenberg
Samuel
S
Brofman
Paulo S
PS
Nakao
Lia S
LS
Correa
Alejandro
A
D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D018421:Cardiomyoplasty; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics; D015870:Gene Expression; D005819:Genetic Markers; D006321:Heart / Q000502:physiology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D015703:Antigens, CD; D018031:Connexin 43; D005819:Genetic Markers; D006834:Hydrazines; D009124:Muscle Proteins; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D010396:Penicillamine