Abstract：
OBJECTIVES:Extracellular nucleotide release at the site of arterial injury mediates the proliferation and migration of vascular smooth muscle cells. Our aim was to investigate the role of the P2Y2 nucleotide receptor (P2Y2R) in neointimal hyperplasia. Approach and Results: Vascular injury was induced by the implantation of a polyethylene cuff around the femoral artery in wild-type and P2Y2R-deficient mice (P2Y2R-/-). Electron microscopy was used to analyze monocyte and lymphocyte influx to the intima 36 h after injury. Compared to wild-type littermates, P2Y2R-/- mice exhibited a 3-fold decreased number of mononuclear leukocytes invading the intima (p < 0.05). Concomitantly, the migration of smooth muscle cells was decreased by more than 60% (p < 0.05), resulting in a sharp inhibition of intimal thickening formation in P2Y2R-/- mice (n = 15) 14 days after cuff placement. In vitro, loss of P2Y2R significantly impaired monocyte migration in response to nucleotide agonists. Furthermore, transgenic rats overexpressing the P2Y2R developed accelerated intimal lesions resulting in more than 95% luminal stenosis (p < 0.05, n = 10). CONCLUSIONS:Loss- and gain-of-function approaches established direct evidence for P2Y2R involvement in neointimal hyperplasia. Specific anti-P2Y2R therapies may be used against restenosis and bypass graft failure.
journal_name
J Vasc Resjournal_title
Journal of vascular researchauthors
Agca Y,Qian S,Agca C,Seye CIdoi
10.1159/000449059subject
Has Abstractpub_date
2016-01-01 00:00:00pages
163-171issue
3-4eissn
1018-1172issn
1423-0135pii
000449059journal_volume
53pub_type
杂志文章abstract：:This study examines the ultrastructural features of diffuse intimal thickenings of human coronary arteries and correlates structural heterogeneity along the radial axis with the distribution and known actions of transforming growth factor beta 1 (TGF-beta 1). Morphometric and immunohistochemical data were collected fr...
journal_title：Journal of vascular research
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doi：10.1159/000159008
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journal_title：Journal of vascular research
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journal_title：Journal of vascular research
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journal_title：Journal of vascular research
pub_type： 杂志文章,评审
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journal_title：Journal of vascular research
pub_type： 杂志文章
doi：10.1159/000505454
更新日期：2020-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1159/000113600
更新日期：2008-01-01 00:00:00
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journal_title：Journal of vascular research
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doi：10.1159/000159245
更新日期：1997-09-01 00:00:00
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journal_title：Journal of vascular research
pub_type： 杂志文章
doi：10.1159/000124283
更新日期：2008-01-01 00:00:00
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journal_title：Journal of vascular research
pub_type： 杂志文章
doi：10.1159/000111072
更新日期：2008-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1159/000082976
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journal_title：Journal of vascular research
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doi：10.1159/000159134
更新日期：1996-01-01 00:00:00
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journal_title：Journal of vascular research
pub_type： 杂志文章
doi：10.1159/000063687
更新日期：2002-05-01 00:00:00
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journal_title：Journal of vascular research
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更新日期：1993-03-01 00:00:00
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journal_title：Journal of vascular research
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doi：10.1159/000158972
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