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
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
收藏
页码:4856 / 4861
页数:6
相关论文
共 29 条
[1]   Notch signaling: Cell fate control and signal integration in development [J].
Artavanis-Tsakonas, S ;
Rand, MD ;
Lake, RJ .
SCIENCE, 1999, 284 (5415) :770-776
[2]   Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex [J].
Ayata, C ;
Dunn, AK ;
Gursoy-Özdemir, Y ;
Huang, ZH ;
Boas, DA ;
Moskowitz, MA .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2004, 24 (07) :744-755
[3]   RAT MIDDLE CEREBRAL-ARTERY OCCLUSION - EVALUATION OF THE MODEL AND DEVELOPMENT OF A NEUROLOGIC EXAMINATION [J].
BEDERSON, JB ;
PITTS, LH ;
TSUJI, M ;
NISHIMURA, MC ;
DAVIS, RL ;
BARTKOWSKI, H .
STROKE, 1986, 17 (03) :472-476
[4]   Notch signalling: a simple pathway becomes complex [J].
Bray, Sarah J. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2006, 7 (09) :678-689
[5]   Transcription, genomes, function [J].
Cho, RJ ;
Campbell, MJ .
TRENDS IN GENETICS, 2000, 16 (09) :409-415
[6]   Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray [J].
Coser, KR ;
Chesnes, J ;
Hur, JY ;
Ray, S ;
Isselbacher, KJ ;
Shioda, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (24) :13994-13999
[7]   Notch3 is required for arterial identity and maturation of vascular smooth muscle cells [J].
Domenga, V ;
Fardoux, P ;
Lacombe, P ;
Monet, M ;
Maciazek, J ;
Krebs, LT ;
Klonjkowski, B ;
Berrou, E ;
Mericskay, M ;
Li, Z ;
Tournier-Lasserve, E ;
Gridley, T ;
Joutel, A .
GENES & DEVELOPMENT, 2004, 18 (22) :2730-2735
[8]   Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase [J].
Endres, M ;
Wang, ZQ ;
Namura, S ;
Waeber, C ;
Moskowitz, MA .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1997, 17 (11) :1143-1151
[9]  
Grove EA, 1998, DEVELOPMENT, V125, P2315
[10]   Notch signaling in blood vessels - Who is talking to whom about what? [J].
Hofmann, Jennifer J. ;
Iruela-Arispe, M. Luisa .
CIRCULATION RESEARCH, 2007, 100 (11) :1556-1568