Thromb Haemost 2019; 119(12): 2014-2024
DOI: 10.1055/s-0039-1697659
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Early Inhibition of P-Selectin/P-Selectin Glycoprotein Ligand-1 Reduces Intimal Hyperplasia in Murine Vein Grafts through Platelet Adhesion

1   Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
2   Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
,
Ya-Ting Chang
1   Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
3   Department of Pediatric, Chang Gung Memorial Hospital, Taoyuan, Taiwan
,
Cih-Yi Yen
2   Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
,
Mariette Lengquist
1   Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
,
Malin Kronqvist
1   Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
,
Einar E. Eriksson
1   Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
,
Ulf Hedin
1   Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
› Author Affiliations
Funding This work was supported by the Swedish Heart-Lung Foundation (project number: 20060691, 20080365, 20080606, and 20090701), the Swedish Research Council (project number: K2009–65X-2233–01–3), Karolinska Institutet, and Chang Gung Memorial Hospital (CMRPG3F1831, CMRPG3F1832). The sponsors were not involved in the study design, data collection, data analysis, and interpretation of data. The sponsors were not involved in the writing of the manuscript and in the decision to submit the manuscript for publication.
Further Information

Publication History

25 January 2019

01 August 2019

Publication Date:
21 October 2019 (online)

Abstract

Inflammatory processes contribute to intimal hyperplasia (IH) and long-term failure of vein grafts used in bypass surgery. Leukocyte recruitment on endothelial cells of vessels during inflammation is regulated by P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1), which also mediates the interaction between platelets and endothelial cells in vein grafts transferred to arteries. However, how this pathway causes IH in vein grafts is unclear. In this study, we used a murine model of vein grafting to investigate P-selectin-mediated platelet adhesion, followed by IH. On the luminal surface of the vein graft, leukocyte recruitment occurred mainly in areas with adhered platelets rather than on endothelial cells without adherent platelets 1 hour after vein grafting. Blockage of either P-selectin or PSGL-1 reduced platelet adhesion and leukocyte recruitment on the luminal surface of vein grafts. Inhibition of the P-selectin pathway in vein grafts significantly reduced platelet-mediated leukocyte recruitment and IH of vein grafts 28 days after surgery. The study demonstrates that functional blockage of the P-selectin/PSGL-1 pathway in the early inflammatory phase after vein grafting reduced leukocyte invasion in the vein graft wall and later IH development. The findings imply an attractive early time window for prevention of vein graft failure by manipulating platelet adhesion.

Authors' Contributions

C.N.T.: Contribution to concept and design, analysis and interpretation of data, and writing manuscript. Y.T.C.: Contribution to concept, interpretation of data, critical writing, and revising the intellectual of content. C.Y.Y.: Contribution to collection and analysis of data. M.L.: Contribution to collection and analysis of data. M.K.: Contribution to collection and analysis of data.


E.E.E.: Contribution to IHC staining and analysis of data. U.H.: Contribution to critical writing and revising the intellectual of content, and final approval of the version to be published.


Note

This manuscript was edited by Wallace Academic Editing.


 
  • References

  • 1 Schwann TA, Zacharias A, Riordan CJ, Durham SJ, Shah AS, Habib RH. Survival and graft patency after coronary artery bypass grafting with coronary endarterectomy: role of arterial versus vein conduits. Ann Thorac Surg 2007; 84 (01) 25-31
  • 2 Schwann TA, Zacharias A, Riordan CJ, Durham SJ, Shah AS, Habib RH. Sequential radial artery grafts for multivessel coronary artery bypass graft surgery: 10-year survival and angiography results. Ann Thorac Surg 2009; 88 (01) 31-39
  • 3 Kiani S, Poston R. Is endoscopic harvesting bad for saphenous vein graft patency in coronary surgery?. Curr Opin Cardiol 2011; 26 (06) 518-522
  • 4 Kopjar T, Dashwood MR. Endoscopic versus “No-Touch” saphenous vein harvesting for coronary artery bypass grafting: a trade-off between wound healing and graft patency. Angiology 2016; 67 (02) 121-132
  • 5 Xu Q, Zhang Z, Davison F, Hu Y. Circulating progenitor cells regenerate endothelium of vein graft atherosclerosis, which is diminished in ApoE-deficient mice. Circ Res 2003; 93 (08) e76-e86
  • 6 Tseng CN, Karlöf E, Chang YT. , et al. Contribution of endothelial injury and inflammation in early phase to vein graft failure: the causal factors impact on the development of intimal hyperplasia in murine models. PLoS One 2014; 9 (06) e98904
  • 7 Fishman JA, Ryan GB, Karnovsky MJ. Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening. Lab Invest 1975; 32 (03) 339-351
  • 8 Phillips JW, Barringhaus KG, Sanders JM. , et al. Single injection of P-selectin or P-selectin glycoprotein ligand-1 monoclonal antibody blocks neointima formation after arterial injury in apolipoprotein E-deficient mice. Circulation 2003; 107 (17) 2244-2249
  • 9 McEver RP, Zhu C. Rolling cell adhesion. Annu Rev Cell Dev Biol 2010; 26: 363-396
  • 10 Schmitt-Sody M, Metz P, Klose A. , et al. In vivo interactions of platelets and leucocytes with the endothelium in murine antigen-induced arthritis: the role of P-selectin. Scand J Rheumatol 2007; 36 (04) 311-319
  • 11 Wagner DD, Frenette PS. The vessel wall and its interactions. Blood 2008; 111 (11) 5271-5281
  • 12 Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res 2007; 100 (12) 1673-1685
  • 13 Varga-Szabo D, Pleines I, Nieswandt B. Cell adhesion mechanisms in platelets. Arterioscler Thromb Vasc Biol 2008; 28 (03) 403-412
  • 14 Massberg S, Enders G, Matos FC. , et al. Fibrinogen deposition at the postischemic vessel wall promotes platelet adhesion during ischemia-reperfusion in vivo. Blood 1999; 94 (11) 3829-3838
  • 15 Khandoga A, Biberthaler P, Enders G. , et al. Platelet adhesion mediated by fibrinogen-intercelllular adhesion molecule-1 binding induces tissue injury in the postischemic liver in vivo. Transplantation 2002; 74 (05) 681-688
  • 16 Leick M, Azcutia V, Newton G, Luscinskas FW. Leukocyte recruitment in inflammation: basic concepts and new mechanistic insights based on new models and microscopic imaging technologies. Cell Tissue Res 2014; 355 (03) 647-656
  • 17 Shukla N, Jeremy JY. Pathophysiology of saphenous vein graft failure: a brief overview of interventions. Curr Opin Pharmacol 2012; 12 (02) 114-120
  • 18 Ed Rainger G, Chimen M, Harrison MJ. , et al. The role of platelets in the recruitment of leukocytes during vascular disease. Platelets 2015; 26 (06) 507-520
  • 19 Pitchford S, Pan D, Welch HC. Platelets in neutrophil recruitment to sites of inflammation. Curr Opin Hematol 2017; 24 (01) 23-31
  • 20 Tamagawa-Mineoka R, Katoh N, Ueda E, Takenaka H, Kita M, Kishimoto S. The role of platelets in leukocyte recruitment in chronic contact hypersensitivity induced by repeated elicitation. Am J Pathol 2007; 170 (06) 2019-2029
  • 21 Wahl RL, Barrett J, Geatti O. , et al. The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage. Cancer Immunol Immunother 1988; 26 (03) 187-201
  • 22 Dietrich H, Hu Y, Zou Y. , et al. Mouse model of transplant arteriosclerosis: role of intercellular adhesion molecule-1. Arterioscler Thromb Vasc Biol 2000; 20 (02) 343-352
  • 23 Salzberg SP, Filsoufi F, Anyanwu A. , et al. Increased neointimal formation after surgical vein grafting in a murine model of type 2 diabetes. Circulation 2006; 114 (1, Suppl): I302-I307
  • 24 Ley K. The role of selectins in inflammation and disease. Trends Mol Med 2003; 9 (06) 263-268
  • 25 Luo W, Campbell A, Wang H. , et al. P-selectin glycoprotein ligand-1 inhibition blocks increased leukocyte-endothelial interactions associated with sickle cell disease in mice. Blood 2012; 120 (18) 3862-3864
  • 26 Malinska A, Perek B, Buczkowski P. , et al. CD68 expression in aortocoronary saphenous vein bypass grafts. Histochem Cell Biol 2013; 140 (02) 183-188
  • 27 Schlitt A, Pruefer D, Buerke U. , et al. Neutrophil adherence to activated saphenous vein and mammary endothelium after graft preparation. Ann Thorac Surg 2006; 81 (04) 1262-1268
  • 28 Steinhubl SR. Platelets as mediators of inflammation. Hematol Oncol Clin North Am 2007; 21 (01) 115-121
  • 29 Thomas MR, Storey RF. The role of platelets in inflammation. Thromb Haemost 2015; 114 (03) 449-458
  • 30 Jung U, Ley K. Mice lacking two or all three selectins demonstrate overlapping and distinct functions for each selectin. J Immunol 1999; 162 (11) 6755-6762
  • 31 Mestas J, Ley K. Monocyte-endothelial cell interactions in the development of atherosclerosis. Trends Cardiovasc Med 2008; 18 (06) 228-232
  • 32 Nieswandt B, Varga-Szabo D, Elvers M. Integrins in platelet activation. J Thromb Haemost 2009; 7 (Suppl. 01) 206-209
  • 33 Rumbaut RE, Thiagarajan P. . In: Platelet-Vessel Wall Interactions in Hemostasis and Thrombosis. San Rafael (CA): 2010
  • 34 Kevil CG, Bullard DC. Roles of leukocyte/endothelial cell adhesion molecules in the pathogenesis of vasculitis. Am J Med 1999; 106 (06) 677-687
  • 35 Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood 1994; 84 (07) 2068-2101
  • 36 Frenette PS, Johnson RC, Hynes RO, Wagner DD. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A 1995; 92 (16) 7450-7454
  • 37 Frenette PS, Denis CV, Weiss L. , et al. P-Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. J Exp Med 2000; 191 (08) 1413-1422
  • 38 Braun OO, Slotta JE, Menger MD, Erlinge D, Thorlacius H. Primary and secondary capture of platelets onto inflamed femoral artery endothelium is dependent on P-selectin and PSGL-1. Eur J Pharmacol 2008; 592 (1-3): 128-132
  • 39 Chico TJ, Chamberlain J, Gunn J. , et al. Effect of selective or combined inhibition of integrins alpha(IIb)beta(3) and alpha(v)beta(3) on thrombosis and neointima after oversized porcine coronary angioplasty. Circulation 2001; 103 (08) 1135-1141
  • 40 Zeiffer U, Schober A, Lietz M. , et al. Neointimal smooth muscle cells display a proinflammatory phenotype resulting in increased leukocyte recruitment mediated by P-selectin and chemokines. Circ Res 2004; 94 (06) 776-784
  • 41 Rossi B, Constantin G. Anti-selectin therapy for the treatment of inflammatory diseases. Inflamm Allergy Drug Targets 2008; 7 (02) 85-93
  • 42 Walker T, Müller I, Raabe C. , et al. Effective silencing of adhesion molecules on venous endothelial cells for protection of venous bypass grafts. Eur J Cardiothorac Surg 2011; 40 (05) 1241-1247