学科主题基础医学
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
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
2013-03-01
DOI10.1161/ATVBAHA.112.300606
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
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 ; 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
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
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 ; 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
引用统计
被引频次:36[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50708
专题北京大学基础医学院_生理学与病理生理学系
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
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GB/T 7714
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-+.
APA Liang, Bin.,Wang, Shuangxi.,Wang, Qilong.,Zhang, Wencheng.,Viollet, Benoit.,...&Zou, Ming-Hui.(2013).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.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,33(3),595-+.
MLA Liang, Bin,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".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 33.3(2013):595-+.
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