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)

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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.