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Transcript 
Vascular Endothelial Adrenomedullin-RAMP2 System Is
Essential for Vascular Integrity and Organ
HomeostasisClinical Perspective
by Teruhide Koyama, Laura Ochoa-Callejero, Takayuki Sakurai, Akiko Kamiyoshi,
Yuka Ichikawa-Shindo, Nobuyoshi Iinuma, Takuma Arai, Takahiro Yoshizawa,
Yasuhiro Iesato, Yang Lei, Ryuichi Uetake, Ayano Okimura, Akihiro Yamauchi,
Megumu Tanaka, Kyoko Igarashi, Yuichi Toriyama, Hisaka Kawate, Ralf H. Adams,
Hayato Kawakami, Naoki Mochizuki, Alfredo Martínez, and Takayuki Shindo
Circulation
Volume 127(7):842-853
February 19, 2013
Copyright © American Heart Association, Inc. All rights reserved.
E-RAMP2−/− mice showed systemic edema and high perinatal mortality, whereas surviving adult
mice showed vascular abnormalities.
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
Adult E-RAMP2−/− mice showed spontaneous vasculitic lesions and premature vascular
senescence.
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
E-RAMP2−/− mice showed fibrosis starting around vessels and progression of organ damage.
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
Adult E-AM−/− mice showed spontaneous vasculitic lesions and glomerulosclerosis.
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
Receptor activity-modifying protein 2 (RAMP2) deficiency enhances endothelial cell (EC)
inflammatory reactions and oxidative stress.
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
Analysis of vascular endothelial RAMP2 deficiency in adults using drug-inducible endothelial
cell (EC)–specific RAMP2 knockout mice (DI-E-RAMP2−/−).
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
Chronic RAMP2-deficiency causes vascular damage and enhanced perivascular inflammation in
DI-E-RAMP2−/− mice.
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
Regulation of endothelial cell (EC) integrity by the adrenomedullin (AM)-RAMP2 system and its
disruption in RAMP2 knockout (KO) mice.
Teruhide Koyama et al. Circulation. 2013;127:842-853
Copyright © American Heart Association, Inc. All rights reserved.
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