Linking Notch signaling to ischemic stroke |
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Authors: | Arboleda-Velasquez Joseph F Zhou Zhipeng Shin Hwa Kyoung Louvi Angeliki Kim Hyung-Hwan Savitz Sean I Liao James K Salomone Salvatore Ayata Cenk Moskowitz Michael A Artavanis-Tsakonas Spyros |
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Affiliation: | Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. |
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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. |
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Keywords: | ischemia Notch3 vascular smooth muscle CADASIL |
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