In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 103, No. 8 ( 2001-02-27), p. 1135-1141
Abstract:
Background —Thrombosis and neointima formation limit the efficacy of coronary angioplasty (PTCA). Clinical trials have implicated the adhesion molecules integrin α IIb β 3 and integrin α v β 3 in these processes. The roles of these molecules in vascular smooth muscle cell adhesion, platelet aggregation, and the thrombotic and neointimal response to oversize porcine PTCA was investigated by use of a selective α IIb β 3 antagonist (lamifiban), a selective α v β 3 antagonist (VO514), and a combined α IIb β 3 /α v β 3 antagonist (G3580). Methods and Results —In vitro, both α v β 3 inhibitors caused dose-dependent inhibition of porcine vascular smooth muscle cell adhesion to vitronectin but not to collagen type IV, fibronectin, or laminin, whereas selective α IIb β 3 inhibition had no effect. Intravenous infusions of either α IIb β 3 inhibitor in swine profoundly inhibited ex vivo platelet aggregation to ADP, whereas selective α v β 3 inhibition had no effect. In a porcine PTCA model, intravenous infusions of the integrin antagonists were administered for 14 days after oversized balloon angioplasty injury. After PTCA, there was regional upregulation of integrin α v β 3 in the developing neointima, as assessed by immunohistochemistry. Six hours after PTCA, obstruction of lumen by thrombus was reduced significantly by α IIb β 3 inhibition compared with either control or α v β 3 inhibition (mean control, 18.7%; VO514, 18.5%; lamifiban, 6.4%; G3580, 7.9%). Twenty-eight days after PTCA, there was a significant reduction of neointima with inhibitors of either integrin (mean intima/media ratio: control, 3.08; VO514, 1.33; lamifiban, 0.97; G3580, 1.32). Conclusions —We conclude that both integrin α IIb β 3 and integrin α v β 3 participate in neointima development after experimental angioplasty.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.103.8.1135
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2001
detail.hit.zdb_id:
1466401-X
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