| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Yutaka Graduate School of Medical Science, Kyushu University, Associate Professor, 大学院・医学研究院, 助教授 (50135349)
ISHIBASHI Hiroaki Graduate School of Dental Science, Kyushu University, Assistant, 大学院・歯学研究院, 助手 (90254630)
SUEISHI Katsuo Graduate School of Medical Science, Kyushu University, Professor, 大学院・医学研究院, 教授 (70108710)
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| Research Abstract |
The patho-physiological role of vascular remodeling in the development and progression of atherosclerosis, thrombosis and proliferative diabetic retinopathy, remains unclear. We studied on the molecular mechanisms of pathological vascular remodeling, and we have got the following results.
1. FGF-2 determines severity of joint disease in adjuvant-induced arthritis in rats. Therefore, the control of FGF-2 function will be an effective therapeutical tool for rheumatoid arthritis.
2. The Sp1 decoy would be effective for regulating tumor growth by simultaneously reducing cancer cell functions including (1) angiogenic growth factor expression, (2) proliferation, and (3) invasiveness. The decoy strategy would be an elective therapeutic tool for cancer.
3. Macrophage infiltration was important for vascular remodeling in rat model of monocrotalin-induced pulmonary hypertension. The control of MCP-1 function by dominant negative mutant 7ND-MCP-1 suppressed macrophage infiltration, and thus this strategy would be provided therapeutical tool for pulmonary hypertension.
4. Neointimal angiogenesis through the biotaxis by cytokine network was important for the progression of atherosclerosis.
5. In a murine model of critical limb ischemia, there were harmonized effects and hierarchy of angiogenic factors (VEGF, HGF, FGF-2) in neovascularization. In addition, FGF-2 gene transfer to ischemic limbs was effective to protect limb necrosis.
These findings and results suggest that angiogenesis play important roles in development of vascular remodeling. Therefore, we will plan to link our results and a clinical application successively. We are now applying, the protocol "Clinical study for angiogenic gene therapy to treat patients with critical limb ischemia using SeV-FGF-2", to Kyushu University ethical committee.
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