Relationship between Platelets and Neutrophil Adhesion and Neointimal Growth after Repeated Arterial Wall Injury Induced by Angioplasty in Pigs

Platelet and neutrophil interactions with injured vascular wall may contribute to restenosis. Their importance was mainly examined following balloon injury of intact arteries. However, dilation of diseased arteries is clinically more relevant and may elicit different responses. We investigated the relationship between platelets and neutrophil adhesion, neointima formation and P-selectin expression on damaged arteries after repeated balloon injury. In an acute single-injury model, 8 pigs were subjected to bilateral carotid angioplasty and sacrificed 1 h later. In a chronic model, 19 pigs were subjected to similar procedures and allowed to recover for 4 weeks; then 18 arteries were redilated at the same previously injured sites (double injury) while the remaining arteries were not redilated and used to investigate the extent and the adhesive properties of the neointima. After single injury, 51Cr-platelet adhesion (×106/cm2) increased significantly from 3.8 ± 0.6 to 45.9 ± 6.5 (p < 0.05) on mildly and deeply injured segments, respectively, and were statistically similar after double injury. After single injury, 111In-neutrophil adhesion (×103/cm2) increased from 226.6 ± 45.5 to 512.5 ± 70.3 (p < 0.05) on mildly and deeply injured segments, and were significantly higher (p < 0.05) after double injury (mild: 1,289.1 ± 227.9 and deep: 2,411.8 ± 333.9). As well, the neo-endothelium expresses P-selectin at 4 weeks and platelet and neutrophil adhesion was directly related to neointimal growth. These results, which indicate ongoing proinflammatory processes 1 month post-angioplasty, suggest that neutrophils may participate in the progression of restenosis.

[1]  F. Roussel,et al.  Lectins as markers of endothelial cells: comparative study between human and animal cells , 1988, Laboratory animals.

[2]  I. Feuerstein,et al.  Role of P-selectin and leukocyte activation in polymorphonuclear cell adhesion to surface adherent activated platelets under physiologic shear conditions (an injury vessel wall model). , 1994, Blood.

[3]  R. Faint.  Platelet-neutrophil interactions: their significance. , 1992, Blood reviews.

[4]  G. Nash,et al.  Selectin-mediated rolling of neutrophils on immobilized platelets. , 1993, Blood.

[5]  R. Virmani,et al.  Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model. , 1994, Journal of the American College of Cardiology.

[6]  S. Weiss.  Tissue destruction by neutrophils. , 1989, The New England journal of medicine.

[7]  D. Faxon,et al.  Pharmacologic prevention of restenosis after coronary angioplasty: review of the randomized clinical trials. , 1993, Coronary artery disease.

[8]  R. Poston,et al.  Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. , 1994, The American journal of pathology.

[9]  P. Libby,et al.  Sustained Activation of Vascular Cells and Leukocytes in the Rabbit Aorta After Balloon Injury , 1993, Circulation.

[10]  D. Bainton,et al.  GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. , 1989, The Journal of clinical investigation.

[11]  L. Koenderman,et al.  Platelet-dependent primary hemostasis promotes selectin- and integrin-mediated neutrophil adhesion to damaged endothelium under flow conditions. , 1996, Blood.

[12]  R E Vlietstra,et al.  Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. , 1992, Journal of the American College of Cardiology.

[13]  M. Diamond,et al.  A subpopulation of Mac-1 (CD11b/CD18) molecules mediates neutrophil adhesion to ICAM-1 and fibrinogen , 1993, The Journal of cell biology.

[14]  R. Cummings,et al.  Role of PSGL-1 binding to selectins in leukocyte recruitment. , 1997, The Journal of clinical investigation.

[15]  H Le Breton,et al.  Role of platelets in restenosis after percutaneous coronary revascularization. , 1996, Journal of the American College of Cardiology.

[16]  F. Neumann,et al.  Neutrophil and platelet activation at balloon-injured coronary artery plaque in patients undergoing angioplasty. , 1996, Journal of the American College of Cardiology.

[17]  E J Topol,et al.  Experimental models of coronary artery restenosis. , 1992, Journal of the American College of Cardiology.

[18]  G. Specchia,et al.  Granulocyte activation after coronary angioplasty in humans. , 1990, Circulation.

[19]  M. Bonneau,et al.  Platelet functions and haemostasis parameters in pigs: absence of side effects of a procedure of general anaesthesia. , 1996, Thrombosis research.

[20]  C. Smith,et al.  Leukocyte activation with platelet adhesion after coronary angioplasty: a mechanism for recurrent disease? , 1995, Journal of the American College of Cardiology.

[21]  C. Benjamin,et al.  Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets , 1992, Nature.

[22]  M. Nobuyoshi,et al.  Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients. , 1991, Journal of the American College of Cardiology.

[23]  V. Fuster,et al.  A dilemma for the 1990s. Choosing appropriate experimental animal model for the prevention of restenosis. , 1992, Circulation.

[24]  R. Guidoin,et al.  Importance of platelets in neutrophil adhesion and vasoconstriction after deep carotid arterial injury by angioplasty in pigs. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[25]  S M Schwartz,et al.  The intima. Soil for atherosclerosis and restenosis. , 1995, Circulation research.

[26]  M. Topham,et al.  Inflammatory roles of P-selectin. , 1993, The Journal of clinical investigation.

[27]  T. Springer,et al.  Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. , 1996, Blood.

[28]  M. Lewis,et al.  Kinetics of smooth muscle cell proliferation and intimal thickening in a pig carotid model of balloon injury. , 1995, Atherosclerosis.

[29]  P. Provost,et al.  Selectin blockade reduces neutrophil interaction with platelets at the site of deep arterial injury by angioplasty in pigs. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[30]  P. Kubes,et al.  A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process. , 1998, Blood.

[31]  R. Guidoin,et al.  Effects of thrombocytopenia and shear rate on neutrophil and platelet deposition on endothelial and medial arterial surfaces. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[32]  G. Nash.  Adhesion between neutrophils and platelets: a modulator of thrombotic and inflammatory events? , 1994, Thrombosis research.

[33]  K. Brown,et al.  Neutrophil-platelet adhesion: relative roles of platelet P-selectin and neutrophil beta2 (DC18) integrins. , 1998, American journal of respiratory cell and molecular biology.

[34]  G. Owens,et al.  A new single-injury model of balloon angioplasty in cholesterol-fed rabbits: beneficial effect of hirudin and comparison with double-injury model. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[35]  E. Topol,et al.  Cell adhesion molecules in coronary artery disease. , 1994, Journal of the American College of Cardiology.

[36]  V. Fuster,et al.  Different response to balloon angioplasty of carotid and coronary arteries: effects on acute platelet deposition and intimal thickening. , 1998, Atherosclerosis.

[37]  J. Zweier,et al.  Coronary angioplasty results in leukocyte and platelet activation with adhesion molecule expression. Evidence of inflammatory responses in coronary angioplasty. , 1997, Journal of the American College of Cardiology.

[38]  J. Tremblay,et al.  The antiadhesive and antithrombotic effects of the nitric oxide donor SIN-1 are combined with a decreased vasoconstriction in a porcine model of balloon angioplasty. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[39]  R. Guidoin,et al.  Increase of neutrophil adhesion and vasoconstriction with platelet deposition after deep arterial injury by angioplasty. , 1995, American heart journal.

[40]  V. Fuster,et al.  Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model. , 1985, Circulation research.

[41]  D Schwartz,et al.  A Cascade Model for Restenosis: A Special Case of Atherosclerosis Progression , 1992, Circulation.

[42]  W. Frishman,et al.  Pathophysiology and pharmacological approaches for prevention of coronary artery restenosis following coronary artery balloon angioplasty and related procedures. , 1997, Progress in cardiovascular diseases.

[43]  E. Topol,et al.  Restenosis—an open file , 1996, Clinical cardiology.

[44]  A. Marcus,et al.  Thromboregulation: multicellular modulation of platelet reactivity in hemostasis and thrombosis , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[45]  R. McEver,et al.  GMP-140 mediates adhesion of stimulated platelets to neutrophils. , 1990, Blood.

[46]  V. Fuster,et al.  The Three Processes Leading to Post PTCA Restenosis: Dependence on the Lesion Substrate , 1995, Thrombosis and Haemostasis.

[47]  D. Heudes,et al.  Repeated balloon injury of rat aorta. A model of neointima with attenuated inhibition by heparin. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[48]  J. Lam,et al.  Neutrophil Implications in Platelet Deposition and Vasoconstriction After Deep Arterial Injury by Angioplasty in Pigs , 1994, Circulation.

[49]  V. Lindner,et al.  Remodeling and neointimal formation in the carotid artery of normal and P-selectin-deficient mice. , 1997, Circulation.