Beta(3)-integrin-deficient mice but not P-selectin-deficient mice develop intimal hyperplasia after vascular injury: correlation with leukocyte recruitment to adherent platelets 1 hour after injury

• Published in: Circulation (New York, N.Y.) N.Y.), 2001-05, Vol.103 (20), p.2501-2507
• Main Authors: Smyth, S S, Reis, E D, Zhang, W, Fallon, J T, Gordon, R E, Coller, B S
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - genetics; Antigens, CD - physiology; Blood Platelets - metabolism; Endothelium, Vascular - physiopathology; Female; Femoral Artery - injuries; Femoral Artery - pathology; Femoral Artery - ultrastructure; Hyperplasia; Integrin beta3; Leukocytes - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Microscopy, Electron; P-Selectin - genetics; P-Selectin - metabolism; P-Selectin - physiology; Platelet Membrane Glycoproteins - deficiency; Platelet Membrane Glycoproteins - genetics; Platelet Membrane Glycoproteins - physiology; Time Factors; Tunica Intima - metabolism; Tunica Intima - pathology
• ISSN: 1524-4539

Intimal hyperplasia contributes to restenosis after percutaneous vascular interventions. Both beta(3)-integrins, alpha(V)beta(3) and alpha(IIb)beta(3) (glycoprotein IIb/IIIa), and leukocytes have been implicated in neointimal formation, based in part on the results obtained using antagonists to 1 or both receptors in animal models. The responses in wild-type mice, beta(3)-integrin-deficient mice, and P-selectin-deficient mice were studied in a model of transluminal endothelial injury of the femoral artery. At 4 weeks, beta(3)-integrin-deficient mice were not protected from developing intimal hyperplasia, whereas P-selectin-deficient mice were protected. Within 1 hour of injury, several layers of platelets deposited on the arteries of wild-type mice and a single layer of platelets deposited on the vessels of beta(3)-integrin-deficient mice; in both cases, leukocytes were recruited to the platelet layer. In P-selectin-deficient mice, the platelet layer was less compact and extended further into the lumen but did not recruit leukocytes. In a model of transluminal arterial injury, absence of early leukocyte recruitment and not deficiency of beta(3)-integrins correlated with a reduction in neointimal formation. Blockade of P-selectins may be an effective therapeutic strategy to decrease restenosis after percutaneous vascular interventions.