北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 心血管所  > 期刊论文
学科主题: 基础医学
题名:
Shear Stress Induces Synthetic-to-Contractile Phenotypic Modulation in Smooth Muscle Cells via Peroxisome Proliferator-Activated Receptor alpha/delta Activations by Prostacyclin Released by Sheared Endothelial Cells
作者: Tsai, Min-Chien1,2; Chen, Lihong3; Zhou, Jing2; Tang, Zhihui4; Hsu, Tzu-Fang2; Wang, Ying3,4; Shih, Yu-Tsung1,2; Peng, Hsin-Hsin2; Wang, Nanping4; Guan, Youfei1; Chien, Shu5,6,7; Chiu, Jeng-Jiann1,2
关键词: endothelial cell ; peroxisome proliferator-activated receptor ; prostacyclin ; shear stress ; smooth muscle cell
刊名: CIRCULATION RESEARCH
发表日期: 2009-08-28
DOI: 10.1161/CIRCRESAHA.109.193656
卷: 105, 期:5, 页:471-480
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Hematology
关键词[WOS]: GAMMA ACTIVATORS ; GENE-EXPRESSION ; PPAR-GAMMA ; DELTA ; MECHANISMS ; MIGRATION ; RAT ; ATHEROSCLEROSIS ; INHIBITION ; ADHESION
英文摘要:

Rationale: Phenotypic modulation of smooth muscle cells (SMCs), which are located in close proximity to endothelial cells (ECs), is critical in regulating vascular function. The role of flow-induced shear stress in the modulation of SMC phenotype has not been well defined.

Objective: The objective was to elucidate the role of shear stress on ECs in modulating SMC phenotype and its underlying mechanism. Methods and

Results: Application of shear stress (12 dyn/cm(2)) to ECs cocultured with SMCs modulated SMC phenotype from synthetic to contractile state, with upregulation of contractile markers, downregulation of proinflammatory genes, and decreased percentage of cells in the synthetic phase. Treating SMCs with media from sheared ECs induced peroxisome proliferator-activated receptor (PPAR)-alpha, -delta, and -gamma ligand binding activities; transfecting SMCs with specific small interfering (si) RNAs of PPAR-alpha and -delta, but not -gamma, inhibited shear induction of contractile markers. ECs exposed to shear stress released prostacyclin (PGI(2)). Transfecting ECs with PGI(2) synthase-specific siRNA inhibited shear-induced activation of PPAR-alpha/delta, upregulation of contractile markers, downregulation of proinflammatory genes, and decrease in percentage of SMCs in synthetic phase. Mice with PPAR-alpha deficiency (compared with control littermates) showed altered SMC phenotype toward a synthetic state, with increased arterial contractility in response to angiotensin II.

Conclusions: These results indicate that laminar shear stress induces synthetic-to-contractile phenotypic modulation in SMCs through the activation of PPAR-alpha/delta by the EC-released PGI(2). Our findings provide insights into the mechanisms underlying the EC-SMC interplays and the protective homeostatic function of laminar shear stress in modulating SMC phenotype. (Circ Res. 2009; 105: 471-480.)

语种: 英语
所属项目编号: ME-097-PP-06 ; 97-3112B-400-006/96-2628-B-400-002-MY3 ; HL080518 ; HL085159 ; 30725033/30530340 ; 30890041
项目资助者: National Health Research Institutes ; National Science Council ; National Heart, Lung, and Blood Institute ; National Science Foundation grants
WOS记录号: WOS:000269384600009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51828
Appears in Collections:基础医学院_心血管所_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
471.full.pdf(1075KB)期刊论文作者接受稿限制开放 联系获取全文

作者单位: 1.Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan
2.Natl Hlth Res Inst, Div Med Engn Res, Miaoli 350, Taiwan
3.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
5.Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
6.Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
7.Univ Calif San Diego, Inst Engn Med, La Jolla, CA 92093 USA

Recommended Citation:
Tsai, Min-Chien,Chen, Lihong,Zhou, Jing,et al. Shear Stress Induces Synthetic-to-Contractile Phenotypic Modulation in Smooth Muscle Cells via Peroxisome Proliferator-Activated Receptor alpha/delta Activations by Prostacyclin Released by Sheared Endothelial Cells[J]. CIRCULATION RESEARCH,2009,105(5):471-480.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Tsai, Min-Chien]'s Articles
[Chen, Lihong]'s Articles
[Zhou, Jing]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Tsai, Min-Chien]‘s Articles
[Chen, Lihong]‘s Articles
[Zhou, Jing]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2018  北京大学医学部 - Feedback
Powered by CSpace