2005 Fiscal Year Final Research Report Summary
gene transferred circulating human vascular progenitor cells transplantation for treatment of myocardial infarction
| Project/Area Number |
16590709
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka City University |
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Principal Investigator |
AKIOKA Kaname Osaka City University, Graduate School of Medicine, Lecturer, 大学院・医学研究科, 講師 (90167833)
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| Co-Investigator(Kenkyū-buntansha) |
YOSIYAMA Minoru Osaka City University, Graduate School of Medicine, associate professor, 大学院・医学研究科, 助教授 (30240956)
OMURA Takashi Osaka City University, Graduate School of Medicine, assistant professor, 大学院・医学研究科, 助手 (70295707)
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| Project Period (FY) |
2004 – 2005
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| Keywords | myocardial infarction / cardiac remodeling / cell therapy / growth factor / signal transduction / transcriptional factor / 遺伝子導入 |
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| Research Abstract |
We have demonstrated as following
1.Angiotensin II induced MCP-1 gene expression in cardiac fibroblasts. The angiotensin II-induced activation of ASK-1 followed by p38MAPK and NF-kB signaling in cardiac fibroblasts is partially involved in myocardial MCP-1
2.Dominant negative mutants of JNK, ASK-1 and c-Jun significantly inhibited PAI-1 mRNA expression and protein synthesis in both cardiomyocytes and fibroblasts. G-protein coupled receptor agonist-induced PAI-1 expression is partially mediated through JNK activation.
3.The human VEGF_<165> gene was transfected to cultured mesenchymal stem cells of Lewis rats using an adenoviral vector. These cells were injected into rat hearts one hour after left coronary artery occlusion. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E/ A ratio and capillary density of the infarcted region were most improved in the VEGF group. In conclusion, this combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.
4.Microbubble destruction with ultrasound can augment neovascularization by transplanted bone marrow-mononuclear cells in the ischemic hindlimb. This microbubble treatment induces collateral vessel formation partly by supplying VEGF.
5.DM reduces the number of circulating EPCs and SMPCs according to its severity, and treatment of DM significantly increases the number of EPCs and SMPCs, which may be involved in angiogenesis and atherosclerosis in diabetes.
6.Pravastatin converted the characteristics of cultured vascular progenitor cells from SMPC to EPC.
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