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Linking Notch signaling to ischemic stroke.


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 a 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.

Pubmed ID: 18347334


  • Arboleda-Velasquez JF
  • Zhou Z
  • Shin HK
  • Louvi A
  • Kim HH
  • Savitz SI
  • Liao JK
  • Salomone S
  • Ayata C
  • Moskowitz MA
  • Artavanis-Tsakonas S


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 25, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: 5 P50 NS10828-32
  • Agency: NCI NIH HHS, Id: CA098402-06
  • Agency: NHGRI NIH HHS, Id: HG003616-01A1
  • Agency: NHLBI NIH HHS, Id: HL052233
  • Agency: NINDS NIH HHS, Id: NS026084-18

Mesh Terms

  • Animals
  • Aorta
  • Arteries
  • Brain
  • Brain Ischemia
  • Cell Separation
  • Disease Susceptibility
  • Flow Cytometry
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Receptors, Notch
  • Regional Blood Flow
  • Signal Transduction
  • Stroke