Intermedin modulates hypoxic pulmonary vascular remodeling by inhibiting pulmonary artery smooth muscle cell proliferation

doi:10.1016/j.pupt.2013.06.004

科研成果详情

题名	Intermedin modulates hypoxic pulmonary vascular remodeling by inhibiting pulmonary artery smooth muscle cell proliferation
作者	Mao, Sun-Zhong1; Fan, Xiao-Fang1; Xue, Feng 1; Chen, Ran 1; Chen, Xuan-Ying 1; Yuan, Gong-Sheng 1; Hu, Liang-Gang1; Liu, Shu Fang 1,2; Gong, Yong-Sheng1
发表日期	2014-02
发表期刊	PULMONARY PHARMACOLOGY & THERAPEUTICS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Hypoxia Pulmonary arterial hypertension Intermedin Proliferation Endoplasmic reticulum stress L-Arginine-NO pathway
其他关键词	ENDOPLASMIC-RETICULUM STRESS ; NITRIC-OXIDE RELEASE ; HYPERTENSION ; DISEASE ; APOPTOSIS ; PEPTIDE ; INJURY ; COPD ; GENE ; INTERMEDIN/ADRENOMEDULLIN-2
摘要	Background: Hypoxic pulmonary arterial hypertension (PAH) is a disabling disease with limited treatment options. Hypoxic pulmonary vascular remodeling is a major cause of hypoxic PAH. Pharmacological agents that can inhibit the remodeling process may have great therapeutic value. Objective: To examine the effect of intermedin (IMD), a new calcitonin gene-related peptide family of peptide, on hypoxic pulmonary vascular remodeling. Methods: Rats were exposed to normoxia or hypoxia (similar to 10% O-2), or exposed to hypoxia and treated with IMD, administered by an implanted mini-osmotic pump (6.5 mu g/rat/day), for 4 weeks. The effects of IMD infusion on the development of hypoxic PAH and right ventricle (RV) hypertrophy, on pulmonary vascular remodeling, on pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis, and on the activations of L-arginine nitric oxide (NO) pathway and endoplasmic reticulum stress apoptotic pathway were examined. Results: Rats exposed to hypoxia developed PAH and RV hypertrophy. IMD treatment alleviated PAH and prevented RV hypertrophy. IMD inhibited hypoxic pulmonary vascular remodeling as indicated by reduced wall thickness and increased lumen diameter of pulmonary arterioles, and decreased muscularization of distal pulmonary vasculature in hypoxia-exposed rats. IMD treatment inhibited PASMC proliferation and promoted PASMC apoptosis. IMD treatment increased tissue level of constitutive NO synthase activity and tissue NO content in lungs, and enhanced L-arginine uptake into pulmonary vascular tissues. IMD treatment increased cellular levels of glucose-regulated protein (GRP) 78 and GRP94, two major markers of endoplasmic reticulum (ER) stress, and increased caspase-12 expression, the ER stress-specific caspase, in lungs and cultured PASMCs. Conclusions: These results demonstrate that IMD treatment attenuates hypoxic pulmonary vascular remodeling, and thereby hypoxic PAH mainly by inhibiting PASMC proliferation. Promotion of PASMC apoptosis may also contribute to the inhibitory effect of IMD. Activations L-arginine-NO pathway and of ER stress-specific apoptosis pathway could be the mechanisms mediating the anti-proliferative and proapoptotic effects of IMD. (C) 2013 Elsevier Ltd. All rights reserved.
资助项目	National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [30871031]; Major State Basic Research Development Program of ChinaNational Basic Research Program of China [2012CB518200]; Natural Science Foundation of Zhejiang Province of ChinaNatural Science Foundation of Zhejiang Province [Y207509, Y2100806]; Science and Technology Foundation of Wenzhou, China [Y20070071]
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
出版地	LONDON
ISSN	1094-5539
EISSN	1522-9629
卷号	27 期号:1 页码:1-9
DOI	10.1016/j.pupt.2013.06.004
页数	9
WOS类目	Pharmacology & Pharmacy ; Respiratory System
WOS研究方向	Pharmacology & Pharmacy ; Respiratory System
WOS记录号	WOS:000331007200001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	23796770
SCOPUSEID	2-s2.0-84892446270
通讯作者地址	[Liu, Shu Fang]Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA.
引用统计	被引频次：23[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/3782
专题	温州医科大学
通讯作者	Liu, Shu Fang
作者单位	1.Wenzhou Med Coll, Inst Hypoxia Med, Wenzhou 325035, Zhejiang, Peoples R China; 2.Feinstein Inst Med Res, Manhasset, NY 11030 USA
第一作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Mao, Sun-Zhong,Fan, Xiao-Fang,Xue, Feng,et al. Intermedin modulates hypoxic pulmonary vascular remodeling by inhibiting pulmonary artery smooth muscle cell proliferation[J]. PULMONARY PHARMACOLOGY & THERAPEUTICS,2014,27(1):1-9.
APA	Mao, Sun-Zhong., Fan, Xiao-Fang., Xue, Feng., Chen, Ran., Chen, Xuan-Ying., ... & Gong, Yong-Sheng. (2014). Intermedin modulates hypoxic pulmonary vascular remodeling by inhibiting pulmonary artery smooth muscle cell proliferation. PULMONARY PHARMACOLOGY & THERAPEUTICS, 27(1), 1-9.
MLA	Mao, Sun-Zhong,et al."Intermedin modulates hypoxic pulmonary vascular remodeling by inhibiting pulmonary artery smooth muscle cell proliferation".PULMONARY PHARMACOLOGY & THERAPEUTICS 27.1(2014):1-9.