2024-03-28T22:16:47Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/77482023-04-19T12:48:09Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
Repisalud
author
Silvestre-Roig, Carlos
author
Fernandez, Patricia
author
Esteban, Vanesa
author
Pello, Oscar M
author
Indolfi, Ciro
author
Rodriguez, Cristina
author
Rodríguez-Calvo, Ricardo
author
Lopez-Maderuelo, Dolores
author
Bauriedel, Gerhard
author
Hutter, Randolph
author
Fuster, Valentin
author
Ibáñez, Borja
author
Redondo, Juan Miguel
author
Martinez-Gonzalez, Jose
author
Andres, Vicente
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Belgian Society of Cardiology
funder
Fundación Mario Losantos del Campo
funder
Fundación Ferrer para la Investigación
funder
Fundación ProCNIC
2019-06-06T10:31:26Z
2019-06-06T10:31:26Z
2013-05
Arterioscler Thromb Vasc Biol. 2013; 33(5):1036-45
1079-5642
http://hdl.handle.net/20.500.12105/7748
23430616
10.1161/ATVBAHA.112.300580
1524-4636
Arteriosclerosis, thrombosis, and vascular biology
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.
eng
Inactivation of nuclear factor-Y inhibits vascular smooth muscle cell proliferation and neointima formation
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/7748/1/InactivationOfNuclearFactor-Y_2013.pdf
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/7748/2/InactivationOfNuclearFactor-Y_2013_Supplemental%20Material.pdf
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InactivationOfNuclearFactor-Y_2013_Supplemental Material.pdf
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https://repisalud.isciii.es/bitstream/20.500.12105/7748/4/InactivationOfNuclearFactor-Y_2013.pdf.txt
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InactivationOfNuclearFactor-Y_2013.pdf.txt
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https://repisalud.isciii.es/bitstream/20.500.12105/7748/6/InactivationOfNuclearFactor-Y_2013_Supplemental%20Material.pdf.txt
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InactivationOfNuclearFactor-Y_2013_Supplemental Material.pdf.txt