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

Circulation. 2001 May 22;103(20):2501-7. doi: 10.1161/01.cir.103.20.2501.


Background: 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.

Methods and results: 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.

Conclusions: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*


  • Antigens, CD
  • Integrin beta3
  • P-Selectin
  • Platelet Membrane Glycoproteins