http://purl.uniprot.org/citations/33714552 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/33714552 | http://www.w3.org/2000/01/rdf-schema#comment | "Background and aimsAtherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability.MethodsChow diet-fed atherosclerosis-prone Apoe-/- mice deficient in Neil3, and NEIL3-abrogated human primary aortic VSMCs were characterized by qPCR, and immunohistochemical and enzymatic-based assays; moreover, single-cell RNA sequencing, mRNA sequencing, and proteomics were used to map the molecular effects of Neil3/NEIL3 deficiency in the aortic VSMC phenotype. Furthermore, BrdU-based proliferation assays and Western blot were performed to elucidate the involvement of the Akt signaling pathway in the transdifferentiation of aortic VSMCs lacking Neil3/NEIL3.ResultsWe show that Neil3 deficiency increases atherosclerotic plaque development without affecting systemic lipids. This observation was associated with a shift in VSMC phenotype towards a proliferating, lipid-accumulating and secretory macrophage-like cell phenotype, without changes in DNA damage. VSMC transdifferentiation in Neil3-deficient mice encompassed increased activity of the Akt signaling pathway, supported by cell experiments showing Akt-dependent proliferation in NEIL3-abrogated human primary aortic VSMCs.ConclusionsOur findings show that Neil3 deficiency promotes atherosclerosis development through non-canonical mechanisms affecting VSMC phenotype involving activation of the Akt signaling pathway."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.atherosclerosis.2021.02.023"xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Yang K."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Bjoras M."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Lauritzen K.H."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Kong X.Y."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Aukrust P."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Nilsen H."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Nyman T.A."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Dahl T.B."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Halvorsen B."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Holm S."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Suganthan R."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Bennett M.R."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Biessen E.A."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Prins J."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Scheffler K."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Holven K.B."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Nygard S."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Bjerkeli V."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Jorgensen H.F."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Floisand Y."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Segers F.M."xsd:string |
http://purl.uniprot.org/citations/33714552 | http://purl.uniprot.org/core/author | "Olsen M.B."xsd:string |