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dc.contributor.authorWalcott, Brian Pen_US
dc.date.accessioned2015-01-05T18:28:11Z
dc.date.issued2014en_US
dc.identifier.citationWalcott, Brian P. 2014. “BMP signaling modulation attenuates cerebral arteriovenous malformation formation in a vertebrate model.” Journal of Cerebral Blood Flow & Metabolism 34 (10): 1688-1694. doi:10.1038/jcbfm.2014.134. http://dx.doi.org/10.1038/jcbfm.2014.134.en
dc.identifier.issn0271-678Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13581214
dc.description.abstractCerebral arteriovenous malformations (AVMs) are vascular anomalies that carry a high risk of stroke and death. To test potential AVM therapies, a reverse genetics approach was used to model AVMs in zebrafish. Antisense morpholino oligonucleotides were used to knockdown activin receptor-like kinase I (alk1), which encodes a transforming growth factor (TGF)-beta family type I receptor implicated in a subset of human AVMs. Knockdown of alk1 caused a spectrum of morphologic, functional, and molecular defects that resemble those seen in humans with AVMs. It was found that losartan, an angiotensin II receptor antagonist, attenuated abnormal blood vessel morphology and systemic manifestations of high-output arteriovenous shunting in vivo. SMAD1 phosphorylation was significantly decreased in alk1 morphants compared with uninjected organisms (0.189±0.0201, 0.429±0.0164, P=0.0002). After treatment, morphant SMAD1 levels approached uninjected levels (0.326±0.0360, P=0.0355) and were significantly higher than those seen in the morphant-control group (P=0.0294). These data suggest that modulating the BMP signaling pathway with losartan, a drug in widespread clinical use in humans as an antihypertensive, may have the potential to be further evaluated as a therapeutic strategy for patients with AVMs.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/jcbfm.2014.134en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269730/pdf/en
dash.licenseLAAen_US
dc.subjectarteriovenous malformationen
dc.subjectlosartanen
dc.subjectmedical therapyen
dc.subjectstrokeen
dc.subjectzebrafishen
dc.titleBMP signaling modulation attenuates cerebral arteriovenous malformation formation in a vertebrate modelen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalJournal of Cerebral Blood Flow & Metabolismen
dash.depositing.authorWalcott, Brian Pen_US
dc.date.available2015-01-05T18:28:11Z
dc.identifier.doi10.1038/jcbfm.2014.134*
dash.contributor.affiliatedWalcott, Brian


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