NOTCH1 is a mechanosensor in adult arteries

被引：240

作者：

Mack, Julia J. ^{[1
]}

Mosqueiro, Thiago S. ^{[2
]}

Archer, Brian J. ^{[3
]}

Jones, William M. ^{[1
]}

Sunshine, Hannah ^{[4
]}

Faas, Guido C. ^{[5
]}

Briot, Anais ^{[1
]}

Aragon, Raquel L. ^{[6
]}

Su, Trent ^{[7
]}

Romay, Milagros C. ^{[1
]}

McDonald, Austin I. ^{[6
]}

Kuo, Cheng-Hsiang ^{[8
]}

Lizama, Carlos O. ^{[9
]}

Lane, Timothy F. ^{[7
,10
,11
]}

Zovein, Ann C. ^{[9
]}

Fang, Yun ^{[8
]}

Tarling, Elizabeth J. ^{[7
,11
,12
]}

Vallim, Thomas Q. de Aguiar ^{[7
,11
,12
]}

Navab, Mohamad ^{[12
]}

Fogelman, Alan M. ^{[12
]}

Bouchard, Louis S. ^{[3
,11
,13
]}

Iruela-Arispe, M. Luisa ^{[1
,11
]}

机构：

[1] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Inst Quantitat & Computat Biol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Interdepl Grad Program Mol Cellular & Integrat Ph, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Inst Mol Biol, Mol Biol Interdisciplinary Grad Program, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA

[8] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[9] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA

[10] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ob Gyn, Los Angeles, CA 90095 USA

[11] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[12] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[13] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家卫生研究院;

关键词：

HEMODYNAMIC SHEAR-STRESS; ENDOTHELIAL-CELLS; IN-VIVO; VASCULAR ENDOTHELIUM; VE-CADHERIN; FLUID-FLOW; CALCIUM; EXPRESSION; COMPLEX; LOCALIZATION;

D O I：

10.1038/s41467-017-01741-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation. NOTCH1 suppression results in changes in expression of genes involved in the regulation of intracellular calcium and proliferation, and preventing the increase of calcium signaling rescues the cell-cell junctional defects. Furthermore, loss of Notch1 in adult endothelium increases hypercholesterolemia- induced atherosclerosis in the descending aorta. We propose that NOTCH1 is atheroprotective and acts as a mechanosensor in adult arteries, where it integrates responses to laminar shear stress and regulates junctional integrity through modulation of calcium signaling.

引用

页数：19

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