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Eur J Cardiothorac Surg 2004;25:188-195
© 2004 Elsevier Science NL
a Stem Cell Research Center, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing 100083, China
b Department of Cardiology, The Third Hospital of Peking University, 49 North Garden Road, Hai Dian District, Beijing 100083, China
c Department of Biochemistry and Molecular Biology, The School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Hai Dian District, Beijing 100083, China
Received 13 June 2003; received in revised form 15 October 2003; accepted 20 October 2003.
* Corresponding author. Tel.: +86-10-8280-2417; fax: +86-10-6201-5582
e-mail: chunyanzhou{at}bjmu.edu.cn
Objective: Heat shock proteins (HSPs) are cytoprotective proteins. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor. This study aimed to elucidate the possible role of cytoprotection and angiogenesis on cardiac function after bone marrow cell transplantation (BMT). Methods: Myocardial infarction was induced in inbred Lewis rats by left anterior descending artery ligation. A total of 5x106 bone marrow-mononuclear cells were transplanted into the ischemic zone by direct injection. At 1, 3, 7, 14 and 28 days post-transplantation, cardiac function was evaluated by echocardiography. The expressions of HSP32, HSP70 and VEGF were assessed by immunofluorescence and RT-PCR. The number of vessels was examined by immunohistochemistry. The differentiation of the transplanted cells was determined by immunofluorescence. Results: Echocardiography showed BMT led to sustained improvement in cardiac function, as assessed by left ventricle ejection fraction and fraction of shortening. Immunofluorescence revealed that the expressions of HSP32, HSP70 and VEGF were promoted in both transplanted bone marrow cells and recipient cardiomyocytes. RT-PCR showed that the mRNA expression levels of HSP32, HSP70 and VEGF in the BMT group were markedly higher in comparison with injection of peripheral blood cells or saline (P<0.01) by day 7. Seven days later, the vessel count showed that angiogenesis had been induced to a significantly greater degree in the BMT groups. Fourteen days later, specific markers for myocardial or vascular endothelial cells were detected in the transplanted bone marrow cells. Conclusions: BMT upregulated the expressions of HSP32, HSP70 and VEGF in both transplanted bone marrow cells and recipient endogenous cardiomyocytes in the early phase post-transplantation. This enhanced cytoprotection and angiogenesis, and contributed to the functional recovery following cardiac infarction. In the late phase, the transplanted bone marrow cells might differentiate into both myocardial and vascular endothelial cells that enhanced the ischemic cardiac function further.
Key Words: Cytoprotection • Angiogenesis • Ischemia • Stem cells • Transplantation
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