English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/36876
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

Rapamycin attenuates atherosclerosis induced by dietary cholesterol in apolipoprotein-deficient mice through a p27Kip1-independent pathway

AuthorsCastro, Claudia; Campistol, Josep M.; Sancho, David; Sánchez Madrid, Francisco; Casals, Elena; Andrés, Vicente
KeywordsRapamycin
Atherosclerosis
p27Kip1
MCP-1/CCL2
Issue DateJan-2004
PublisherElsevier
CitationAtherosclerosis 172(1): 31-38 (2004)
AbstractActivation of immune cells and dysregulated growth and motility of vascular smooth muscle cells contribute to neointimal lesion development during the pathogenesis of vascular obstructive disease. Inhibition of these processes by the immunosuppressant rapamycin is associated with reduced neointimal thickening in the setting of balloon angioplasty and chronic graft vessel disease (CGVD). In this study, we show that rapamycin elicits a marked reduction of aortic atherosclerosis in apolipoprotein E (apoE)-null mice fed a high-fat diet despite sustained hypercholesterolemia. This inhibitory effect of rapamycin coincided with diminished aortic expression of the positive cell cycle regulatory proteins proliferating cell nuclear antigen and cyclin-dependent kinase 2. Moreover, rapamycin prevented the normal upregulation of the proatherogenic monocyte chemoattractant protein-1 (MCP-1, CCL2) seen in the aorta of fat-fed mice. Previous studies have implicated the growth suppressor p27Kip1 in the antiproliferative and antimigratory activities of rapamycin in vitro. However, our studies with fat-fed mice doubly deficient for p27Kip1 and apoE disclosed an antiatherogenic effect of rapamycin comparable with that found in apoE-null mice with an intact p27Kip1 gene. Taken together, these findings extend the therapeutic application of rapamycin from the restenosis and CGVD models to the setting of diet-induced atherosclerosis. Our results suggest that rapamycin-dependent atheroprotection occurs through a p27Kip1-independent pathway that involves reduced expression of positive cell cycle regulators and MCP-1 within the arterial wall.
Description8 páginas, 5 figuras.-- El documento en word es la versión post-print.
Publisher version (URL)http://dx.doi.org/10.1016/j.atherosclerosis.2003.09.003
URIhttp://hdl.handle.net/10261/36876
DOI10.1016/j.atherosclerosis.2003.09.003
ISSN0021-9150
Appears in Collections:(IBV) Artículos
Files in This Item:
File Description SizeFormat 
Atherosclerosis 172 31-38 (2004).doc106,5 kBMicrosoft WordView/Open
Show full item record
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.