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学科主题: 临床医学
题名:
Intramuscular gene transfer of CGRP inhibits neointimal hyperplasia after balloon injury in the rat abdominal aorta
作者: Wang, W; Sun, W; Wang, X
关键词: restenosis ; apoptosis ; vascular smooth muscle cells ; proliferation ; nitric oxide
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
发表日期: 2004-10-01
DOI: 10.1152/ajpheart.00168.2004
卷: 287, 期:4, 页:H1582-H1589
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Physiology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Physiology
关键词[WOS]: SMOOTH-MUSCLE-CELLS ; NITRIC-OXIDE SYNTHASE ; CARDIOVASCULAR-SYSTEM ; VASCULAR-DISEASE ; CYCLIC-AMP ; KAPPA-B ; PEPTIDE ; APOPTOSIS ; ADRENOMEDULLIN ; INDUCTION
英文摘要:

CGRP is a well-known neuropeptide that has various protective effects on cardiovascular system. Our previous studies have shown that CGRP inhibits vascular smooth muscle cell (VSMC) proliferation in vitro. The present study aimed to explore the role of the CGRP in neointimal formation after balloon injury in the rat aortic wall and the underlying mechanism. Gene transfer of CGRP was performed with the use of intramuscular electroporation in a balloon-injured rat aorta model. Apoptosis in VSMCs was determined by electrophoresis assessment of DNA fragmentation and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay. Overexpression of the CGRP gene significantly inhibited the neointimal formation after balloon injury compared with the mock transfer, as assessed by the intima-to-media ratio 14 days after balloon injury (29.2 +/- 3.7% vs. 52.7 +/- 5.4%; n = 9 - 12, P < 0.05). In addition, CGRP gene expression increased the number of apoptotic cells in the neointima in vivo 14 days after balloon injury. Similarly, the addition of bioactive CGRP and the nitric oxide donor induced similar apoptosis in cultured VSMCs. The antagonist of the CGRP(1) receptor and inhibitors of cAMP-PKA and nitric oxide blocked CGRP-mediated apoptosis. Furthermore, CGRP gene transfer increased inducible nitric oxide synthase and p53 but decreased PCNA and Bcl-2 protein levels in balloon-injured rat aorta. Our data demonstrated that CGRP potently inhibited neointimal thickening in the rat aorta, at least in part through its distinct effects on apoptosis and proliferation of VSMCs both in vivo and in vitro. Therefore, delivery of the CGRP gene may have therapeutic implications in limiting vascular restenosis.

语种: 英语
WOS记录号: WOS:000223895800019
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59072
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100083, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Physiol, Beijing 100083, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Educ Minist, Key Lab Mol Cardiovasc Sci, Beijing 100083, Peoples R China

Recommended Citation:
Wang, W,Sun, W,Wang, X. Intramuscular gene transfer of CGRP inhibits neointimal hyperplasia after balloon injury in the rat abdominal aorta[J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY,2004,287(4):H1582-H1589.
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