A novel therapeutic approach for vascular failure by adrenomedullin-RAMP2 system

2014 Fiscal Year Final Research Report

• Project/Area Number: 25893225
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto Prefectural University of Medicine (2014); International University of Health and Welfare (2013)
• Principal Investigator: KOYAMA Teruhide 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40711362)
• Research Collaborator: SHINDO Takayuki 信州大学, 医学系研究科, 教授
• Project Period (FY): 2013-08-30 – 2015-03-31
• Keywords: アドレノメデュリン / RAMP2 / 血管内皮細胞 / 動脈硬化 / 血管恒常性

Outline of Final Research Achievements

Adrenomedullin (AM) is a vasoactive peptide and its clinical applications are expected. AM’s receptor CLR interacts with one of the receptor activity-modifying proteins (RAMP1-3). We have suggested that vascular function of AM is mainly regulated by RAMP2. To clarify whether RAMP2 could be an alternative therapeutic target of AM, we generated and analyzed genetically engineered mice of RAMP2. We found that neointimal formation after vascular injury was markedly enhanced in vascular endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-) compared with control mice. DI-E-RAMP2-/- also showed higher degree of oxidative stress and increased expression of inflammatory cytokines. Next, we generated vascular endothelial cell-specific RAMP2-overexpressing transgenic mice (E-RMAP2Tg). Contrary, intimal hyperplasia and inflammation was suppressed in E-RMAP2Tg compared with wild-type mice. These results suggest that RAMP2 could a novel therapeutic target for vascular failure.

Free Research Field

循環器内科学