Endothelial Nogo-B regulates sphingolipid biosynthesis to promote pathological cardiac hypertrophy during chronic pressure overload

Registro completo de metadados
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorZhang, Yi-
Autor(es): dc.creatorHuang, Yan-
Autor(es): dc.creatorCantalupo, Anna-
Autor(es): dc.creatorAzevedo, Paula S.-
Autor(es): dc.creatorSiragusa, Mauro-
Autor(es): dc.creatorBielawski, Jacek-
Autor(es): dc.creatorGiordano, Frank J.-
Autor(es): dc.creatorDi Lorenzo, Annarita-
Data de aceite: dc.date.accessioned2021-03-10T23:52:20Z-
Data de disponibilização: dc.date.available2021-03-10T23:52:20Z-
Data de envio: dc.date.issued2018-11-26-
Data de envio: dc.date.issued2018-11-26-
Data de envio: dc.date.issued2016-04-21-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1172/jci.insight.85484-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/162123-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/162123-
Descrição: dc.descriptionWe recently discovered that endothelial Nogo-B, a membrane protein of the ER, regulates vascular function by inhibiting the rate-limiting enzyme, serine palmitoyltransferase (SPT), in de novo sphingolipid biosynthesis. Here, we show that endothelium-derived sphingolipids, particularly sphingosine-1-phosphate (S1P), protect the heart from inflammation, fibrosis, and dysfunction following pressure overload and that Nogo-B regulates this paracrine process. SPT activity is upregulated in banded hearts in vivo as well as in TNF-alpha-activated endothelium in vitro, and loss of Nogo removes the brake on SPT, increasing local S1P production. Hence, mice lacking Nogo-B, systemically or specifically in the endothelium, are resistant to the onset of pathological cardiac hypertrophy. Furthermore, pharmacological inhibition of SPT with myriocin restores permeability, inflammation, and heart dysfunction in Nogo-A/B-deficient mice to WT levels, whereas SEW2871, an S1P 1 receptor agonist, prevents myocardial permeability, inflammation, and dysfunction in WT banded mice. Our study identifies a critical role of endothelial sphingolipid biosynthesis and its regulation by Nogo-B in the development of pathological cardiac hypertrophy and proposes a potential therapeutic target for the attenuation or reversal of this clinical condition.-
Formato: dc.format18-
Idioma: dc.languageen-
Publicador: dc.publisherAmer Soc Clinical Investigation Inc-
Relação: dc.relationJci Insight-
Direitos: dc.rightsclosedAccess-
Título: dc.titleEndothelial Nogo-B regulates sphingolipid biosynthesis to promote pathological cardiac hypertrophy during chronic pressure overload-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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