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Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4856-61. doi: 10.1073/pnas.0709867105. Epub 2008 Mar 17.

Linking Notch signaling to ischemic stroke.

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  • 1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Abstract

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.

PMID:
18347334
[PubMed - indexed for MEDLINE]
PMCID:
PMC2290794
Free PMC Article
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