Matches in SemOpenAlex for { <https://semopenalex.org/work/W4220970606> ?p ?o ?g. }
- W4220970606 abstract "Abstract We previously conducted genetic analyses, and identified semaphorin signaling as associating with coronary artery disease. Of the semaphorins, human vascular expression profiling suggested SEMA3F as potentially linked to atherogenesis. In hyperlipidemic mice, SEMA3F reduced aortic lesion area, and increased fibrous cap endothelial content, leading to plaque stability. In a disturbed-flow-mediated endothelial dysfunction-driven lesion model, the absence of Sema3f increased plaques, further implicating SEMA3F in endothelial function. Monocyte adhesion to Sema3f -/- vascular endothelial cells (VECs) was elevated, driven by increased PI3K activity, leading to increased NF-κB-mediated elevation in VCAM1 and ICAM1 expression, suggesting that SEMA3F reduces VEC PI3K activity. Increased permeability led to increased monocyte transmigration through Sema3f -/- VECs, and mTOR phosphorylation was decreased, suppressing VE-cadherin expression and cell-cell adherens junction stability. Actomyosin fiber formation was decreased in Sema3f -/- VECs, which was reversed by PI3K inhibition, further implicating SEMA3F in adherens junction stability. In Sema3f -/- vascular smooth muscle cells (VSMCs), active PI3K was also increased. PI3K facilitates VSMC proliferation, migration, and pro-atherogenic phenotype switching, which were reduced by SEMA3F. In agreement, in a model of VSMC proliferation and migration-induced neointima formation, SEMA3F reduced plaques. Semaphorin3F is causally atheroprotective. SEMA3F’s suppression of VEC and VSMC PI3K activation may contribute to its atheroprotection." @default.
- W4220970606 created "2022-04-03" @default.
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- W4220970606 date "2022-03-24" @default.
- W4220970606 modified "2023-10-01" @default.
- W4220970606 title "Semaphorin3F reduces vascular endothelial and smooth muscle cell PI3K activation and decreases neointimal plaque formation" @default.
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- W4220970606 doi "https://doi.org/10.1101/2022.03.22.485288" @default.
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