[Transplantation of bone marrow cells upregulated vascular endothelial growth factor and its receptor and improved ischemic myocardial function].
OBJECTIVE
To investigate the possible mechanisms of improving ischemic myocardial function by transplantation of bone marrow cells in a rat ischemic heart model.


METHODS
Myocardial infarction was induced in inbred Lewis rats by left anterior descending artery ligation. Bone marrow cells were injected into an ischemic zone (BMI group). On days 1, 3, 7, 14 and 28 post-transplantation, the expressions of vascular endothelial growth factor (VEGF) and its receptor (Flk-1) and the differentiation of transplanted cells were determined by immunofluorescence and RT-PCR. The number of vessels was examined by immunohistochemistry. The cardiac function was evaluated by hemodynamics.


RESULTS
Immunofluorescence microscopy of hearts from BMI group revealed that expressions of VEGF and Flk-1 were promoted within cardiomyocytes in the infarction zone, the peri-infarct zone and in some transplanted bone marrow cells. RT-PCR also showed that mRNA expression levels of VEGF and Flk-1 in BMI group were significantly higher than those of the control group, reached the highest level on days 3 and 14 post-transplantation, and then gradually declined. On days 7, 14 and 28, the vessel count showed the number of blood vessels in the BMI group was greater than that of the control group at the same time, and the cardiac function in the BMI group was improved more significantly than that of the control group. After day 14, the specific markers for myocardium or vascular endothelial cells were detected in the transplanted bone marrow cells.


CONCLUSIONS
BMI improved the acute ischemic cardiac function by both upregulating the expressions of VEGF and Flk-1 in transplanted BMCs and recipient endogenous cardiomyocytes that enhanced angiogenesis.
Zhang
Shaoheng
S
Peking University, Stem Cell Research Center, Beijing, China.
Jia
Zhuqing
Z
Guo
Jingxuan
J
Zhang
Ping
P
Ma
Kangtao
K
Wang
Shuling
S
Liu
Yonggang
Y
Li
Lingsong
L
Zhou
Chunyan
C
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003331:Coronary Vessels; D006321:Heart; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium; D032383:Myocytes, Cardiac; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040301:Vascular Endothelial Growth Factor Receptor-2