p66Shc Deletion Confers Vascular Protection in Advanced Atherosclerosis in Hypercholesterolemic Apolipoprotein E Knockout Mice

被引：46

作者：

Martin-Padura, Ines ^{[3
,4
]}

de Nigris, Filomena ^{[5
,7
]}

Migliaccio, Enrica ^{[3
,4
]}

Mansueto, Gelsomina ^{[6
]}

Minardi, Simone ^{[3
,4
]}

Rienzo, Monica ^{[5
,7
]}

Lerman, Lilach O. ^{[8
]}

Stendardo, Massimo ^{[3
,4
]}

Giorgio, Marco ^{[3
,4
]}

De Rosa, Gaetano ^{[6
]}

Pelicci, Pier Giuseppe ^{[3
,4
]}

Napoli, Claudio ^{[1
,2
,5
]}

机构：

[1] Univ Naples Federico II, Dept Gen Pathol, Div Clin Pathol, Sch Med, Naples, Italy

[2] Univ Naples Federico II, Sch Med, Excellence Res Ctr Cardiovasc Dis, Naples, Italy

[3] EIO, Milan, Italy

[4] IFOM, Milan, Italy

[5] Univ Naples 2, Dept Gen Pathol, Div Clin Pathol, Sch Med, I-80138 Naples, Italy

[6] Univ Naples Federico II, Dept Human Pathol, Naples, Italy

[7] Univ Naples 2, Excellence Res Ctr Cardiovasc Dis, Sch Med, I-80138 Naples, Italy

[8] Mayo Clin, Coll Med, Div Nephrol & Hypertens, Rochester, MN USA

来源：

ENDOTHELIUM-JOURNAL OF ENDOTHELIAL CELL RESEARCH | 2008年 / 15卷 / 5-6期

关键词：

Atherosclerosis; ApoE; p66Shc;

D O I：

10.1080/10623320802487791

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Previous studies showed that p66Shc -/- 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-/- /p66Shc -/-). 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-/-/p66Shc +/+ were significantly larger than those observed in ApoE-/-/p66Shc -/-. Accordingly, the lipid-laden macrophage foam cells and oxidation-specific epitopes in ApoE-/-/p66shc +/+ HFD-treated groups were higher than those observed in normal diet (ND)-treated groups. Thus, p66Shc -/- 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-/-/p66Shc -/- background treated with a very HFD in comparison to ApoE-/-/p66Shc +/+ (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.

引用

页码：276 / 287

页数：12

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