Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/23430616http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23430616http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Atherosclerosis and restenosis are multifactorial diseases associated with abnormal vascular smooth muscle cell (VSMC) proliferation. Nuclear factor-Y (NF-Y) plays a major role in transcriptional activation of the CYCLIN B1 gene (CCNB1), a key positive regulator of cell proliferation and neointimal thickening. Here, we investigated the role of NF-Y in occlusive vascular disease.

Approach and results

We performed molecular and expression studies in cultured cells, animal models, and human tissues. We find upregulation of NF-Y and cyclin B1 expression in proliferative regions of murine atherosclerotic plaques and mechanically induced lesions, which correlates with higher binding of NF-Y to target sequences in the CCNB1 promoter. NF-YA expression in neointimal lesions is detected in VSMCs, macrophages, and endothelial cells. Platelet-derived growth factor-BB, a main inductor of VSMC growth and neointima development, induces the recruitment of NF-Y to the CCNB1 promoter and augments both CCNB1 mRNA expression and cell proliferation through extracellular signal-regulated kinase 1/2 and Akt activation in rat and human VSMCs. Moreover, adenovirus-mediated overexpression of a NF-YA-dominant negative mutant inhibits platelet-derived growth factor-BB-induced CCNB1 expression and VSMC proliferation in vitro and neointimal lesion formation in a mouse model of femoral artery injury. We also detect NF-Y expression and DNA-binding activity in human neointimal lesions.

Conclusions

Our results identify NF-Y as a key downstream effector of the platelet-derived growth factor-BB-dependent mitogenic pathway that is activated in experimental and human vasculoproliferative diseases. They also identify NF-Y inhibition as a novel and attractive strategy for the local treatment of neointimal formation induced by vessel denudation."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.112.300580"xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Fernandez P."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Hutter R."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Rodriguez C."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Esteban V."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Andres V."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Martinez-Gonzalez J."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Redondo J.M."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Ibanez B."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Fuster V."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Bauriedel G."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Pello O.M."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Lopez-Maderuelo M.D."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Rodriguez-Calvo R."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Indolfi C."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/author"Silvestre-Roig C."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/pages"1036-1045"xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/title"Inactivation of nuclear factor-Y inhibits vascular smooth muscle cell proliferation and neointima formation."xsd:string
http://purl.uniprot.org/citations/23430616http://purl.uniprot.org/core/volume"33"xsd:string
http://purl.uniprot.org/citations/23430616http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23430616
http://purl.uniprot.org/citations/23430616http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23430616
▶