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学科主题: 基础医学
题名:
Aberrant Endoplasmic Reticulum Stress in Vascular Smooth Muscle Increases Vascular Contractility and Blood Pressure in Mice Deficient of AMP-Activated Protein Kinase-alpha 2 In Vivo
作者: Liang, Bin1; Wang, Shuangxi1; Wang, Qilong1; Zhang, Wencheng1; Viollet, Benoit3,4; Zhu, Yi5; Zou, Ming-Hui2
关键词: AMPK ; ER stress ; hypertension ; vascular smooth muscle
刊名: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
发表日期: 2013-03-01
DOI: 10.1161/ATVBAHA.112.300606
卷: 33, 期:3, 页:595-+
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Hematology ; Cardiovascular System & Cardiology
关键词[WOS]: POLYCYSTIC-OVARY-SYNDROME ; CELL-CYCLE PROGRESSION ; METABOLIC RISK-FACTORS ; ER STRESS ; ENDOTHELIAL DYSFUNCTION ; INSULIN-RESISTANCE ; CARDIAC DAMAGE ; NORMAL MENSES ; KINASE ; METFORMIN
英文摘要:

Objective-The endoplasmic reticulum (ER) plays a critical role in ensuring proper folding of newly synthesized proteins. Aberrant ER stress is reported to play a causal role in cardiovascular diseases. However, the effects of ER stress on vascular smooth muscle contractility and blood pressure remain unknown. The aim of this study was to investigate whether aberrant ER stress causes abnormal vasoconstriction and consequent high blood pressure in mice.

Methods and Results-ER stress markers, vascular smooth muscle contractility, and blood pressure were monitored in mice. Incubation of isolated aortic rings with tunicamycin or MG132, 2 structurally unrelated ER stress inducers, significantly increased both phenylephrine-induced vasoconstriction and the phosphorylation of myosin light chain (Thr18/Ser19), both of which were abrogated by pretreatment with chemical chaperones or 5-Aminoimidazole-4-carboxamide ribonucleotide and metformin, 2 potent activators for the AMP-activated protein kinase. Consistently, administration of tauroursodeoxycholic acid or 4-phenyl butyric acid, 2 structurally unrelated chemical chaperones, in AMP-activated protein kinase-alpha 2 knockout mice lowered blood pressure and abolished abnormal vasoconstrictor response of AMP-activated protein kinase-alpha 2 knockout mice to phenylephrine. Consistently, tunicamycin (0.01 mu g/g per day) infusion markedly increased both systolic and diastolic blood pressure, both of which were ablated by coadministration of 4-phenyl butyric acid. Furthermore, 4-phenyl butyric acid or tauroursodeoxycholic acid, which suppressed angiotensin II infusion-induced ER stress markers in vivo, markedly lowered blood pressure in angiotensin II-infused mice in vivo.

Conclusion-We conclude that ER stress increases vascular smooth muscle contractility resulting in high blood pressure, and AMP-activated protein kinase activation mitigates high blood pressure through the suppression of ER stress in vivo. (Arterioscler Thromb Vasc Biol. 2013;33:595-604.)

语种: 英语
所属项目编号: HL074399 ; HL079584 ; HL080499 ; HL08920 ; HL096032 ; HL105157 ; HL110488
项目资助者: National Institutes of Health RO1 ; American Diabetes Association ; Warren Endowed Chair of the University of Oklahoma Health Science Center ; Chinese National Science Foundation ; American Heart Association
WOS记录号: WOS:000314890200025
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50708
Appears in Collections:基础医学院_生理学与病理生理学系_期刊论文

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作者单位: 1.INSERM, U1016, Paris, France
2.Univ Oklahoma, Sect Mol Med, Dept Med, Hlth Sci Ctr, Oklahoma City, OK 73104 USA
3.Univ Oklahoma, Dept Biochem & Mol Biol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA
4.Univ Paris 05, Inst Cochin, CNRS, UMR8104, Paris, France
5.Peking Univ, Dept Physiol, Hlth Sci Ctr, Beijing, Peoples R China

Recommended Citation:
Liang, Bin,Wang, Shuangxi,Wang, Qilong,et al. Aberrant Endoplasmic Reticulum Stress in Vascular Smooth Muscle Increases Vascular Contractility and Blood Pressure in Mice Deficient of AMP-Activated Protein Kinase-alpha 2 In Vivo[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2013,33(3):595-+.
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