@article{oai:soar-ir.repo.nii.ac.jp:00007175, author = {Yang, Lei and Sakurai, Takayuki and Kamiyoshi, Akiko and Ichikawa-Shindo, Yuka and Kawate, Hisaka and Yoshizawa, Takahiro and Koyama, Teruhide and Iesato, Yasuhiro and Uetake, Ryuichi and Yamauchi, Akihiro and Tanaka, Megumu and Toriyama, Yuichi and Igarashi, Kyoko and Shindo, Takayuki}, journal = {JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY}, month = {Jun}, note = {信州大学博士(医学)・学位論文・平成25年3月31日授与(甲第942号)・楊 磊, 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. (C) 2013 Elsevier Ltd. All rights reserved., Article, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY. 59(0):55-66 (2013)}, pages = {55--66}, title = {Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury}, volume = {59}, year = {2013} }