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Bone marrow mesenchymal stem cells overexpressing GATA-4 improve cardiac function following myocardial infarction.
- Source :
- Perfusion; Nov2019, Vol. 34 Issue 8, p696-704, 9p, 3 Charts, 2 Graphs
- Publication Year :
- 2019
-
Abstract
- Introduction: The present study aimed to examine whether GATA-4 overexpressing bone marrow mesenchymal stem cells can improve cardiac function in a murine myocardial infarction model compared with bone marrow mesenchymal stem cells alone. Methods: A lentiviral-based transgenic system was used to generate bone mesenchymal stem cells which stably expressed GATA-4 (GATA-4-bone marrow mesenchymal stem cells). Apoptosis and the myogenic phenotype of the bone marrow mesenchymal stem cells were measured using Western blot and immunofluorescence assays co-cultured with cardiomyocytes. Cardiac function, bone marrow mesenchymal stem cell homing, cardiac cell apoptosis, and vessel number following transplantation were assessed, as well as the expression of c-Kit. Results: In GATA-4-bone marrow mesenchymal stem cells-cardiomyocyte co-cultures, expression of myocardial-specific antigens, cTnT, connexin-43, desmin, and α-actin was increased compared with bone marrow mesenchymal stem cells alone. Caspase 8 and cytochrome C expression was lower, and the apoptotic rate was significantly lower in GATA-4 bone marrow mesenchymal stem cells. Cardiac function following myocardial infarction was also increased in the GATA-4 bone marrow mesenchymal stem cell group as demonstrated by enhanced ejection fraction and left ventricular fractional shortening. Analysis of the cardiac tissue revealed that the GATA-4 bone marrow mesenchymal stem cell group had a greater number of DiR-positive cells suggestive of increased homing and/or survival. Transplantation with GATA-4-bone marrow mesenchymal stem cells significantly increased the number of blood vessels, decreased the proportion of apoptotic cells, and increased the mean number of cardiac c-kit-positive cells. Conclusion: GATA-4 overexpression in bone marrow mesenchymal stem cells exerts anti-apoptotic effects by targeting cytochrome C and Fas pathways, promotes the aggregation of bone marrow mesenchymal stem cells in cardiac tissue, facilitates angiogenesis, and effectively mobilizes c-kit-positive cells following myocardial infarction, leading to the improvement of cardiac function after MI. [ABSTRACT FROM AUTHOR]
- Subjects :
- ANALYSIS of variance
ANIMAL experimentation
APOPTOSIS
BIOLOGICAL models
BONE marrow
CARDIAC output
GENE expression
IMMUNOHISTOCHEMISTRY
MICE
MYOCARDIAL infarction
POLYMERASE chain reaction
RNA
STATISTICS
STEM cells
TRANSCRIPTION factors
WESTERN immunoblotting
DATA analysis
DATA analysis software
CASPASES
DESCRIPTIVE statistics
Subjects
Details
- Language :
- English
- ISSN :
- 02676591
- Volume :
- 34
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Perfusion
- Publication Type :
- Academic Journal
- Accession number :
- 139585462
- Full Text :
- https://doi.org/10.1177/0267659119847442