title: Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury.
abstract: Neointimal hyperplasia is the primary lesion underlying atherosclerosis and restenosis after percutaneous coronary intervention. Calcitonin gene-related peptide (CGRP) is produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. Originally identified as a strongly vasodilatory neuropeptide, CGRP is now known to be a pleiotropic peptide widely distributed in various organs and tissues. Our aim was to investigate the possibility that CGRP acts as an endogenous vasoprotective molecule. We compared the effect of CGRP deficiency on neointimal formation after wire-induced vascular injury in wild-type and CGRP knockout (CGRP-/-) mice. We found that neointimal formation after vascular injury was markedly enhanced in CGRP-/- mice, which also showed a higher degree of oxidative stress, as indicated by reduced expression of nitric oxide synthase, increased expression of p47phox, and elevated levels of 4HNE, as well as greater infiltration of macrophages. In addition, CGRP-deficiency led to increased vascular smooth muscle cell (VSMC) proliferation within the neointima. By contrast, bone marrow-derived cells had little or no effect on neointimal formation in CGRP-/-mice. In vitro analysis showed that CGRP-treatment suppressed VSMC proliferation, migration, and ERK1/2 activity. These results clearly demonstrate that endogenous CGRP suppresses the oxidative stress and VSMC proliferation induced by vascular injury. As a vasoprotective molecule, CGRP could be an important therapeutic target in cardiovascular disease.
authors: Department of Cardiovascular Research, Shinshu University Graduate School of Medicine, Japan.
authors: Lei
authors: L
authors: Yang
authors: Takayuki
authors: T
authors: Sakurai
authors: Akiko
authors: A
authors: Kamiyoshi
authors: Yuka
authors: Y
authors: Ichikawa-Shindo
authors: Hisaka
authors: H
authors: Kawate
authors: Takahiro
authors: T
authors: Yoshizawa
authors: Teruhide
authors: T
authors: Koyama
authors: Yasuhiro
authors: Y
authors: Iesato
authors: Ryuichi
authors: R
authors: Uetake
authors: Akihiro
authors: A
authors: Yamauchi
authors: Megumu
authors: M
authors: Tanaka
authors: Yuichi
authors: Y
authors: Toriyama
authors: Kyoko
authors: K
authors: Igarashi
authors: Takayuki
authors: T
authors: Shindo
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D057772:Vascular System Injuries / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*
chemical_list: D015740:Calcitonin Gene-Related Peptide