Cx43 in mesenchymal stem cells promotes angiogenesis of the infarcted heart independent of gap junctions

Wang,De‑Guo; Zhang,Feng‑Xiang; Chen,Ming‑Long; Zhu,Hong‑Jun; Yang,Bing; Cao,Ke‑Jiang

doi:10.3892/mmr.2014.1923

Cx43 in mesenchymal stem cells promotes angiogenesis of the infarcted heart independent of gap junctions

Authors:
- De‑Guo Wang
- Feng‑Xiang Zhang
- Ming‑Long Chen
- Hong‑Jun Zhu
- Bing Yang
- Ke‑Jiang Cao
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Affiliations: Department of Gerontology, The Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: January 28, 2014 https://doi.org/10.3892/mmr.2014.1923
Pages: 1095-1102

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Abstract

Mesenchymal stem cells (MSCs) with elevated levels of connexin 43 (Cx43) have been shown to exhibit improved protection for ischemic hearts. However, it remains unclear whether Cx43 is involved in the paracrine actions of angiogenesis, the major mechanism of cell therapy. In the present study, an in vitro model with deprivation of oxygen and a murine myocardial infarction model with permanent ligation of the left anterior‑descending (LAD) coronary artery were used to determine whether gap junctions in MSCs promote angiogenesis. It was observed that MSCs that overexpressed Cx43 (MSCs‑Cx43), improve the cardiac function of infarcted myocardium as compared with control MSCs (MSCs‑vector) and MSCs with Cx43 knocked down by small interfering RNA (MSCs‑siCx43), accompanied with a reduction of infarct size and an increase in the vascular density and maturity. Increased levels of representative angiogenic factors [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)] were produced by MSCs‑Cx43 compared with MSCs‑siCx43 in vivo and in vitro. However, neither Cx43 formed gap junction specific inhibitor (Cx43 mimetic peptide) or gap junction opener (antiarrhythmic peptide) affected the production of VEGF and bFGF in MSCs under hypoxic stress. These data support the hypothesis that Cx43 in MSCs promotes angiogenesis in the infarcted heart, independent of gap junction formation.

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