Linking Notch signaling to ischemic stroke

被引：88

作者：

Arboleda-Velasquez, Joseph F. ^{[1
]}

Zhou, Zhipeng ^{[2
]}

Shin, Hwa Kyoung ^{[2
]}

Louvi, Angeliki ^{[3
]}

Kim, Hyung-Hwan ^{[5
]}

Savitz, Sean I. ^{[2
,4
]}

Liao, James K. ^{[5
]}

Salomone, Salvatore ^{[2
]}

Ayata, Cenk ^{[2
]}

Moskowitz, Michael A. ^{[2
]}

Artavanis-Tsakonas, Spyros ^{[1
,6
]}

机构：

[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[2] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA

[3] Yale Univ, Sch Med, Program Neurogent, New Haven, CT 06520 USA

[4] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA

[5] Harvard Univ, Sch Med, Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA 02139 USA

[6] Coll France, F-75231 Paris, France

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 12期

关键词：

ischemia; Notch3; vascular smooth muscle; CADASIL;

D O I：

10.1073/pnas.0709867105

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：

Vascular smooth muscle cells (SMCs) have been implicated in the pathophysiology of stroke, the third most common cause of death and the leading cause of long-term neurological disability in the world. However, there is little insight into the underlying cellular pathways that link SMC function to brain ischemia susceptibility. Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype.

引用

页码：4856 / 4861

页数：6

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