Apelin promotes mesenchymal stem cells survival and vascularization under hypoxic-ischemic condition in vitro involving the upregulation of vascular endothelial growth factor.
Mesenchymal stem cells (MSCs) transplantation has been regarded as an optimal therapeutic approach for cardiovascular disease. However, the inferior survival and low vascularization potential of these cells in the local infarct site reduce the therapeutic efficacy. In this study, we investigated the influence of apelin on MSCs survival and vascularization under hypoxic-ischemic condition in vitro and explored the relevant mechanism.



MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells of the third passage were divided into MSCs and MSCs+apelin groups. In the MSCs+apelin group, MSCs were stimulated with apelin-13 (5μM). The two groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24h, using normoxia (20% O2) as a negative control during the process. Human umbilical vein endothelial cells (HUVECs) were used and incubated with conditioned media from both groups to promote vascularization for another 6h. Vascular densities were assessed and relevant biomarkers were detected thereafter.



Compared with MSCs group, MSCs+apelin group presented more rapid growth. The proliferation rate was much higher. Cells apoptosis percentage was significantly declined both under normoxic and hypoxic conditions. Media produced from MSCs+apelin group triggered HUVECs to form a larger number of vascular branches on matrigel. The expression and secretion of vascular endothelial growth factor (VEGF) were significantly increased.



Apelin could effectively promote MSCs survival and vascularization under hypoxic-ischemic condition in vitro, and this procedure was associated with the upregulation of VEGF. This study provides a new perspective for exploring novel approaches to enhance MSCs survival and vascularization potential.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
Jingying
J
Hou
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
Tingting
T
Zhong
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
Tianzhu
T
Guo
The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, China.
Changqing
C
Miao
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
Changqing
C
Zhou
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
Huibao
H
Long
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
Hao
H
Wu
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.
Shaoxin
S
Zheng
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China.
Lei
L
Wang
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China. Electronic address: tongwang316@163.com.
Tong
T
Wang
D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; C495199:apelin-13 peptide
Marrow mesenchymal stem cells; Putative receptor protein related to the angiotensin receptor AT1 endogenous ligand; Vascular endothelial growth factor; Vascularization