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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2008-12-9
pubmed:abstractText
Previous studies showed that p66(Shc-/-) mice on a very-high-fat diet (HFD) had reduced oxidative stress, foam cell, and early atherosclerotic lesion formation. Here, the authors have used hypercholesterolemic apolipoprotein E (ApoE(-/-)) mice to investigate the role of p66Shc deletion in advanced atheroma. The authors generated mice deficient of both ApoE and p66Shc genes (ApoE(-/-) /p66(Shc-/-)). They used microsatellite polymerase chain reaction (PCR) analysis to analyze the genetic background and considered only animals with a constant percentages of C57B6L and 129SV background strands (it was obtained the 50.3% +/- 6.4% of C57B6L background). Computer-assisted analysis revealed that advanced atherosclerotic lesions in ApoE(-/-)/p66(Shc+/+) were significantly larger than those observed in ApoE(-/-)/p66(Shc-/-). Accordingly, the lipid-laden macrophage foam cells and oxidation-specific epitopes in ApoE(-/-)/p66(shc+/+) HFD-treated groups were higher than those observed in normal diet (ND)-treated groups. Thus, p66(Shc-/-) plays an important protective role also against advanced atherosclerotic lesion formation. Finally, the authors have used microarray to investigate major changes in gene expression in aortas of mice with ApoE(-/-)/p66(Shc-/-) background treated with a very HFD in comparison to ApoE(-/-)/p66(Shc+/+) (these data have been confirmed by by real-time PCR and immunohistochemistry). DAVID (Database for Annotation, Visualization and Integrated Discovery) analysis revealed that CD36 antigen (CD36), tissue inhibitor of metalloproteinase 2 (TIMP2), apolipoprotein E (ApoE), acetyl-coenzyme A acetyltransferase 1 (ACAT1), and thrombospondin 1 (THBS1) can be involved in p66 deletion-dependent vascular protection through the adipocytokine/lipid signaling pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1029-2373
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
276-87
pubmed:meshHeading
pubmed-meshheading:19065319-Adipokines, pubmed-meshheading:19065319-Animals, pubmed-meshheading:19065319-Aorta, pubmed-meshheading:19065319-Apolipoproteins E, pubmed-meshheading:19065319-Atherosclerosis, pubmed-meshheading:19065319-Dietary Fats, pubmed-meshheading:19065319-Disease Models, Animal, pubmed-meshheading:19065319-Down-Regulation, pubmed-meshheading:19065319-Foam Cells, pubmed-meshheading:19065319-Food, Formulated, pubmed-meshheading:19065319-Gene Deletion, pubmed-meshheading:19065319-Gene Expression Regulation, pubmed-meshheading:19065319-Genetic Predisposition to Disease, pubmed-meshheading:19065319-Genotype, pubmed-meshheading:19065319-Hypercholesterolemia, pubmed-meshheading:19065319-Lipid Metabolism, pubmed-meshheading:19065319-Male, pubmed-meshheading:19065319-Mice, pubmed-meshheading:19065319-Mice, Inbred C57BL, pubmed-meshheading:19065319-Mice, Knockout, pubmed-meshheading:19065319-Shc Signaling Adaptor Proteins, pubmed-meshheading:19065319-Signal Transduction
pubmed:articleTitle
p66Shc deletion confers vascular protection in advanced atherosclerosis in hypercholesterolemic apolipoprotein E knockout mice.
pubmed:affiliation
European Institute of Oncology (EIO), Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't