2007 Fiscal Year Final Research Report Summary
Pathophysiological Mechanisms of Angiogenesis-Related Diseases
| Project/Area Number |
18390115
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Chiba University |
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Principal Investigator |
YONEMITSU Yoshikazu Chiba University, Gradoatie School of Medieine, Department of Gene Therapy, Professor (40315065)
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| Co-Investigator(Kenkyū-buntansha) |
SUEISHI Katsuo Kyushu University, Graduate School of Medical Sciences, Department of Pathology, Professor (70108710)
NAKAGAWA Kazunori Kyushu University, Graduate School of Medical Sciences, Department of Pathology, Assistant Professor (50217668)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Generation and Development of Blood vessels / Generation of Lymphatic vessels / Sendai Virus Vector / MCP-1 / FGF-2 / PDGF-BB / Spred |
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| Research Abstract |
During 2-years' research project, we performed integrated research approach, from cell, animal model, to human materials, to investigate the genetic, molecular, and pathophysiological mechanisms of angiogenesis-related diseases.
Major findings obtained in this project were as follows; 1. We clarified the critical role of monocyte/macrophage chamoattractant protein-1 (MCP 1) during revascularization mediated by FGF-2 (published in Arteriosclr Thromb Vasc Biol 2006). 2. We identified a new single nucleotide polymorphism (SNP) of protein kinase-C (PKC) eta critically related to cerebral infarction (published in Nature Genetics 2006). 3. We discovered the deposition of oxidized lipids at subintimal layer prior to macrophage accumulation in very early process of human atherosclerosis (published in Arteriosclr Thromb Vasc Biol 2006). 4. We established a double knockout mouse line for endogenous growth factor inhibitors, namely Spred-1 and Spred-2. Mice of this line exhibited embryonic lethal at day 13.5, that were caused by abnormal development of lymphatic vessels due to VEGFR3 signaling (Mol Cell Biol 2007). 5. A ligand of VEGRR1, placental growth factor (PlGF), support the function of VEGF-A during FGF-2-mediated angiogenesis (Atherosclerosis 2008). 6. FGF-2 upregulates VEGF-C expression to form functional capillary and lymphatic network associated with PDGF-BB expression (manuscript under submission). 7. Statins restore vascular endothelial function under diabetic state nitric oxide (NO)/ endothelial NO syntase (eNOS), but not capillary maturation by PDGF-BB, is critical in this process.
These findings should contribute the understanding of and new therapeutic approach to atherosclerotic diseases and metabolic syndrome.
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