title: Linking Notch signaling to ischemic stroke.
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.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Arboleda-Velasquez
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zhou
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Angeliki
authors.initials: A
authors.lastname: Louvi
authors.forename: Hyung-Hwan
authors.initials: HH
authors.lastname: Kim
authors.forename: Sean I
authors.initials: SI
authors.lastname: Savitz
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
authors.forename: Salvatore
authors.initials: S
authors.lastname: Salomone
authors.forename: Cenk
authors.initials: C
authors.lastname: Ayata
authors.forename: Michael A
authors.initials: MA
authors.lastname: Moskowitz
authors.forename: Spyros
authors.initials: S
authors.lastname: Artavanis-Tsakonas
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology / Q000648:ultrastructure; D001158:Arteries / Q000473:pathology / Q000648:ultrastructure; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D002469:Cell Separation; D004198:Disease Susceptibility; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000378:metabolism*; D012039:Regional Blood Flow; D015398:Signal Transduction; D020521:Stroke / Q000150:complications* / Q000378:metabolism* / Q000473:pathology
chemical_list: C499374:NOTCH3 protein, human; C499373:Notch3 protein, mouse; D000071656:Receptor, Notch3; D051880:Receptors, Notch