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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 RIS Download

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 | Receptor, Notch3 | Receptors, Notch | Regional Blood Flow | Signal Transduction | Stroke

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Associated grants

  • Agency: NINDS NIH HHS, Id: R37 NS026084
  • Agency: NINDS NIH HHS, Id: NS026084-18
  • Agency: NINDS NIH HHS, Id: R01 NS026084
  • Agency: NHLBI NIH HHS, Id: HL052233
  • Agency: NCI NIH HHS, Id: R01 CA098402
  • Agency: NCI NIH HHS, Id: CA098402-06
  • Agency: NINDS NIH HHS, Id: P50 NS010828
  • Agency: NHGRI NIH HHS, Id: R01 HG003616
  • Agency: NHLBI NIH HHS, Id: R01 HL052233
  • Agency: NINDS NIH HHS, Id: 5 P50 NS10828-32
  • Agency: NHGRI NIH HHS, Id: HG003616-01A1

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