[Upregulating the expression of angiogenesis-related genes by transplanting autologous mononuclear bone marrow cells into myocardial infarction scar and the periphery].
OBJECTIVE
To detect the regulation of angiogenic genes involved in the processes of collateral development.


METHODS
Myocardial infarction (MI) scar was induced by cryoinjury in New Zealand rabbits. Four weeks after MI, 24 hours before cell transplantation, bone marrow was aspirated from the right thigh bone and mononuclear bone marrow cells (BMCs) were isolated by Ficoll density gradient centrifugation. Then the mononuclear BMCs (n = 8) or IMDM culture medium (n = 8) were transplanted into infarction scar and the periphery. Four weeks after mononuclear BMCs transplantation, DNA microarray analysis was performed to detect the regulation of angiogenesis-related genes in infarction scar and the periphery. And the differences of angiogenic genes expression were compared among several important growth factors by Western blot.


RESULTS
DNA microarray analysis showed the detail regulation of genes involved in the angiogenic processes. There were 15 genes upregulated over 3 times in the infarction scar. In addition, we also found more genes are involved in the process of angiogenesis in its periphery than in the infarction scar (40 genes vs. 15 genes). Western bolt analysis further demonstrated that mononuclear BMCs transplantation was capable of increasing the levels of VEGF, FGF and Angiopoietin-I expression in the infarction scar and its periphery, compared with the control group, P < 0.05.


CONCLUSIONS
These findings indicate that the natural angiogenic processes leading to collateral development are extremely complex, since many kinds of bone marrow-derived growth factors involved in the processes after mononuclear BMCs transplantation into infarction sites.
Sun
Yong-xin
YX
Department of Cardiovascular Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhao
Qiang
Q
Wang
Yi-qing
YQ
Yang
Cheng
C
Pan
Cui-zhen
CZ
Han
Pei-pei
PP
Chen
Rui-zhen
RZ
Yang
Ying-zhen
YZ
Wang
Ke-qiang
KQ
Ge
Jun-bo
JB
D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011817:Rabbits; D015854:Up-Regulation; D020257:Ventricular Remodeling