Back to Search
Start Over
Vasoprotective Activities of the Adrenomedullin-RAMP2 System in Endothelial Cells.
- Source :
- Endocrinology; May 2017, Vol. 158 Issue: 5 p1359-1372, 14p
- Publication Year :
- 2017
-
Abstract
- Neointimal hyperplasia is the primary lesion underlying atherosclerosis and restenosis after coronary intervention. We previously described the essential angiogenic function of the adrenomedullin (AM)-receptor activity-modifying protein (RAMP) 2 system. In the present study, we assessed the vasoprotective actions of the endogenous AM-RAMP2 system using a wire-induced vascular injury model. We found that neointima formation and vascular smooth muscle cell proliferation were enhanced in RAMP2+/- male mice. The injured vessels from RAMP2+/- mice showed greater macrophage infiltration, inflammatory cytokine expression, and oxidative stress than vessels from wild-type mice and less re-endothelialization. After endothelial cell-specific RAMP2 deletion in drug-inducible endothelial cell-specific RAMP2-/- (DI-E-RAMP2-/-) male mice, we observed markedly greater neointima formation than in control mice. In addition, neointima formation after vessel injury was enhanced in mice receiving bone marrow transplants from RAMP2+/- or DI-E-RAMP2-/- mice, indicating that bone marrow-derived cells contributed to the enhanced neointima formation. Finally, we found that the AM-RAMP2 system augmented proliferation and migration of endothelial progenitor cells. These results demonstrate that the AM-RAMP2 system exerts crucial vasoprotective effects after vascular injury and could be a therapeutic target for the treatment of vascular diseases.
Details
- Language :
- English
- ISSN :
- 00137227 and 19457170
- Volume :
- 158
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Endocrinology
- Publication Type :
- Periodical
- Accession number :
- ejs51113020
- Full Text :
- https://doi.org/10.1210/en.2016-1531