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.
| 原文 | English |
|---|---|
| 文章編號 | 1620 |
| 期刊 | Nature communications |
| 卷 | 8 |
| 發行號 | 1 |
| DOIs | |
| 出版狀態 | Published - 2017 十二月 1 |
指紋
All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
引用此文
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NOTCH1 is a mechanosensor in adult arteries. / Mack, Julia J.; Mosqueiro, Thiago S.; Archer, Brian J.; Jones, William M.; Sunshine, Hannah; Faas, Guido C.; Briot, Anais; Aragón, Raquel L.; Su, Trent; Romay, Milagros C.; McDonald, Austin I.; Kuo, Cheng Hsiang; Lizama, Carlos O.; Lane, Timothy F.; Zovein, Ann C.; Fang, Yun; Tarling, Elizabeth J.; De Aguiar Vallim, Thomas Q.; Navab, Mohamad; Fogelman, Alan M.; Bouchard, Louis S.; Iruela-Arispe, M. Luisa.
於: Nature communications, 卷 8, 編號 1, 1620, 01.12.2017.研究成果: Article
TY - JOUR
T1 - NOTCH1 is a mechanosensor in adult arteries
AU - Mack, Julia J.
AU - Mosqueiro, Thiago S.
AU - Archer, Brian J.
AU - Jones, William M.
AU - Sunshine, Hannah
AU - Faas, Guido C.
AU - Briot, Anais
AU - Aragón, Raquel L.
AU - Su, Trent
AU - Romay, Milagros C.
AU - McDonald, Austin I.
AU - Kuo, Cheng Hsiang
AU - Lizama, Carlos O.
AU - Lane, Timothy F.
AU - Zovein, Ann C.
AU - Fang, Yun
AU - Tarling, Elizabeth J.
AU - De Aguiar Vallim, Thomas Q.
AU - Navab, Mohamad
AU - Fogelman, Alan M.
AU - Bouchard, Louis S.
AU - Iruela-Arispe, M. Luisa
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85034623470&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034623470&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01741-8
DO - 10.1038/s41467-017-01741-8
M3 - Article
C2 - 29158473
AN - SCOPUS:85034623470
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1620
ER -