Overexpression of inducible nitric oxide synthase impairs the survival of bone marrow stem cells transplanted into rat infarcted myocardium.
OBJECTIVE
Inducible nitric oxide synthase (iNOS) over-expression is considered critical to the death of transplanted cells in infarcted myocardium. The present study was to investigate the effect of iNOS on the survival of transplanted bone marrow mesenchymal stem cells (BMSCs) in infarcted myocardium.


RESULTS
Male rat BMSCs were injected into the infarct region of female rat hearts at 1 hour (H1, group A), day 3 (D3, group B), and day 7 (D7, group C) after coronary artery ligation, and harvested on D7 after transplantation. Myocardial iNOS expression was significantly increased shortly after coronary ligation with its peak on D3, and returned to baseline at D7. The cell survival rates were 6.2%, 2.1%, and 8.3% in group A, B, and C, respectively, one week after transplantation as assessed by detecting the Y-chromosome sry sequence in the infarct region. There was no significant difference in the survival rates between D7 and week 6 after cell transplantation in group A. Treating the animals in group B with the selective iNOS inhibitor 1400 W significantly increased the survival rate (from 1.8% to 4.2%). Apoptosis level of the transplanted cells was also significantly reduced with 1400 W treatment in group B.


CONCLUSIONS
BMSC transplantation on H1 and D7 after coronary ligation might be the optimal time for cell survival. The loss of transplanted BMSCs in the infarcted myocardium was partially due to increased apoptosis and iNOS overexpression. Selective iNOS inhibition early in myocardial infarction may increase the cell viability.
Department of Cardiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Hong-Min
HM
Li
Department of Cardiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Lin
L
Liu
Department of Cardiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Xiang
X
Mei
Yongcheng Hospital, Ningbo, Zhejiang Province, China.
Huajun
H
Chen
Davis Heart & Lung Research Institute and Division of Cardiovascular Medicine, Ohio State University Medical Center, Columbus, OH, USA.
Zhenguo
Z
Liu
Department of Cardiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address: xuezhao_cn@163.com.
Xue
X
Zhao
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology*; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology / Q000601:surgery*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
Bone marrow stem cell; Cell transplantation; Inducible nitric oxide synthase; Myocardial infarction; Nitric oxide