Abstract:
:Monocyte chemoattractant protein-1 (MCP-1) stimulates the formation of a collateral circulation on arterial occlusion. The present study served to determine whether these proarteriogenic properties of MCP-1 are preserved in hyperlipidemic apolipoprotein E-deficient (apoE-/-) mice and whether it affects the systemic development of atherosclerosis. A total of 78 apoE-/- mice were treated with local infusion of low-dose MCP-1 (1 microg/kg per week), high-dose MCP-1 (10 microg/kg per week), or PBS as a control after unilateral ligation of the femoral artery. Collateral hindlimb flow, measured with fluorescent microspheres, significantly increased on a 1-week high-dose MCP-1 treatment (PBS 22.6+/-7.2%, MCP-1 31.3+/-10.3%; P<0.05). These effects were still present 2 months after the treatment (PBS 44.3+/-4.6%, MCP-1 56.5+/-10.4%; P<0.001). The increase in collateral flow was accompanied by an increase in the number of perivascular monocytes/macrophages on MCP-1 treatment. However, systemic CD11b expression by monocytes also increased, as did monocyte adhesion at the aortic endothelium and neointimal formation (intima/media ratio, 0.097+/-0.011 [PBS] versus 0.257+/-0.022 [MCP-1]; P<0.0001). Moreover, Sudan IV staining revealed an increase in aortic atherosclerotic plaque surface (24.3+/-5.2% [PBS] versus 38.2+/-9.5% [MCP-1]; P<0.01). Finally, a significant decrease in the percentage of smooth muscle cells was found in plaques (15.0+/-5.2% [PBS] versus 5.8+/-2.3% [MCP-1]; P<0.001). In conclusion, local infusion of MCP-1 significantly increases collateral flow on femoral artery ligation in apoE-/- mice up to 2 months after the treatment. However, the local treatment did not preclude systemic effects on atherogenesis, leading to increased atherosclerotic plaque formation and changes in cellular content of plaques.
journal_name
Circ Resjournal_title
Circulation researchauthors
van Royen N,Hoefer I,Böttinger M,Hua J,Grundmann S,Voskuil M,Bode C,Schaper W,Buschmann I,Piek JJdoi
10.1161/01.res.0000052313.23087.3fsubject
Has Abstractpub_date
2003-02-07 00:00:00pages
218-25issue
2eissn
0009-7330issn
1524-4571journal_volume
92pub_type
杂志文章abstract:RATIONALE:Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years of age paralleling the increased incidence of hypertension and metabolic conditions further inactivate Sirt3 because of increased NADH (nicotinamide adenine dinucleotide, reduced form) and acetyl-CoA levels. Sirt3 impair...
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更新日期:1994-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1990-02-01 00:00:00
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journal_title:Circulation research
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更新日期:2017-03-03 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2015-05-22 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.87.12.e61
更新日期:2000-12-08 00:00:00
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journal_title:Circulation research
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更新日期:2008-12-05 00:00:00
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journal_title:Circulation research
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更新日期:2020-05-22 00:00:00
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更新日期:2006-09-29 00:00:00
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更新日期:2008-08-29 00:00:00
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更新日期:1994-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1997-11-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2014-06-20 00:00:00
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pub_type: 杂志文章,多中心研究
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