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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. Copyright © 2017 Endocrine Society.


Xian Xian, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Megumu Tanaka, Teruhide Koyama, Hisaka Kawate, Lei Yang, Tian Liu, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo. Vasoprotective Activities of the Adrenomedullin-RAMP2 System in Endothelial Cells. Endocrinology. 2017 May 01;158(5):1359-1372

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PMID: 28324104

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