| Project/Area Number |
21790713
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Shinshu University |
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Principal Investigator |
SHINDO Yuka Shinshu University, 医学系研究科, 研究員 (50507506)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アドレノメデュリン / RAMP / 血管 / 血管新生 / 血管内皮細胞 |
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| Research Abstract |
Adrenomedullin (AM) is a pleiotropic peptide involved in both the pathogenesis of cardiovascular diseases and circulatory homeostasis. In the present study, we generated and analyzed knockout mice of RAMP2, a small membrane protein and a modulator of G-protein coupled receptor (GPCR), and showed that it is the key determinant of the vascular functions of AM.
To analyze the roles of vascular RAMP2 directly, we generated vascular endothelial cell-specific RAMP2 knockout mice (E-RAMP2-/-). Most E-RAMP2-/-were lethal at later-gestation with systemic edema and vascular fragility. Contrary, small number of the E-RAMP2-/-can survive. In the survived E-RAMP2-/-, the RAMP2 expression in endothelial cells was kept at 20% of wild-type littermates. In adult E-RAMP2-/-spontaneous occurrence of vasculitis lesions was detected throughout the body with aging. Furthermore, E-RAMP2-/-showed severe organ fibrosis with the enhancement of oxidative stress.
These results show that RAMP2 is the key determinant of the vascular functions of AM ; RAMP2 is essential for the vaso- and organ-protective effects of AM in adult as well as for the angiogenesis during development.
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