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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
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
2009-08-28
DOI10.1161/CIRCRESAHA.109.193656
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
WOS记录号WOS:000269384600009
项目编号ME-097-PP-06 ; 97-3112B-400-006/96-2628-B-400-002-MY3 ; HL080518 ; HL085159 ; 30725033/30530340 ; 30890041
资助机构National Health Research Institutes ; National Science Council ; National Heart, Lung, and Blood Institute ; National Science Foundation grants
引用统计
被引频次:51[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51828
专题北京大学基础医学院_心血管所
北京大学基础医学院
北京大学第二临床医学院_风湿免疫科
北京大学口腔医学院_第二门诊部
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
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GB/T 7714
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.
APA Tsai, Min-Chien.,Chen, Lihong.,Zhou, Jing.,Tang, Zhihui.,Hsu, Tzu-Fang.,...&Chiu, Jeng-Jiann.(2009).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.CIRCULATION RESEARCH,105(5),471-480.
MLA Tsai, Min-Chien,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".CIRCULATION RESEARCH 105.5(2009):471-480.
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