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Poster Abstract Presentations

Abstract 178: Platelet Cd40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes

Dirk Lievens, Tom Seijkens, Marijke J Kuijpers, Holger Winkels, Helene Hartwig, Linda Beckers, Remco T Megens, Louis Boon, Randolph J Noelle, Norbert Gerdes, Johan W Heemskerk, Oliver Soehnlein, Christian Weber, Esther Lutgens
Arteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:A178
Dirk Lievens
IPEK, LMU, Munich, Germany
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Tom Seijkens
Med Biochemistry, AMC, Amsterdam, Netherlands
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Marijke J Kuijpers
CARIM, Univ of Maastricht, Maastricht, Netherlands
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Holger Winkels
IPEK, LMU, Munich, Germany
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Helene Hartwig
IPEK, LMU, Munich, Germany
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Linda Beckers
Med Biochemistry, AMC, Amsterdam, Netherlands
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Remco T Megens
IPEK, LMU, Munich, Germany
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Louis Boon
Bioceros, Bioceros, Utrecht, Netherlands
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Randolph J Noelle
Cntr for Transplantation, Kings College, London, United Kingdom
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Norbert Gerdes
IPEK, LMU, Munich, Germany
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Johan W Heemskerk
CARIM, Univ of Maastricht, Maastricht, Netherlands
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Oliver Soehnlein
IPEK, LMU, Munich, Germany
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Christian Weber
IPEK, LMU, Munich, Germany
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Esther Lutgens
IPEK, LMU, Munich, Germany
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Abstract

Beyond their eminent role in hemostasis and thrombosis, platelets are recognized as mediators of inflammation and protagonists of atherogenesis. Here we investigated the inflammatory propensity of platelet-specific expression of CD40, the most common receptor for CD40L. Besides its presence on immune cells and other cell types, CD40 is constitutively expressed on platelets where its function is largely unknown.

CD40-deficient platelets exhibited impaired thrombin-induced activation, reflected by decreased P-selectin expression and αIIbβ3 integrin activation. Compared to infusion of activated Apoe-/- platelets, injection of activated Cd40-/-Apoe-/- platelets caused a >2-fold decrease in plaque size in the aortic arch (Apoe-/- platelets 18.3x104 ± 2.7x104 μm2 vs Cd40-/-Apoe-/- platelets 6.7 x104 ± 2.1 x104 μm2, Vehicle 9.8 x104 ± 2.8 x104 μm2, p<0.05) of Apoe-/- mice. Intravital microscopy of carotid arteries revealed impaired platelet adhesion and impeded leukocyte recruitment to the arterial wall of mice injected with activated Cd40-/-Apoe-/- platelets, which was accompanied by a decrease in endothelial VCAM-1 expression. Moreover, Cd40-/-Apoe-/- platelets displayed a reduced capacity to form platelet-leukocyte aggregates in vitro with these co-incubations releasing less IL-1β. Interestingly, once a thrombus had formed, leukocyte recruitment into thrombi was hampered in Cd40-/-Apoe-/- thrombi.

This study ascribes an essential function to platelet CD40 in atherosclerosis. Besides platelet activation, platelet CD40 induces activation of leukocytes and endothelial cells, thereby promoting inflammation and consequently atherogenesis.

  • Platelet
  • CD40 costimulation
  • atherosclerosis
  • © 2013 by American Heart Association, Inc.
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Arteriosclerosis, Thrombosis, and Vascular Biology
May 2018, Volume 38, Issue 5
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    Abstract 178: Platelet Cd40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes
    Dirk Lievens, Tom Seijkens, Marijke J Kuijpers, Holger Winkels, Helene Hartwig, Linda Beckers, Remco T Megens, Louis Boon, Randolph J Noelle, Norbert Gerdes, Johan W Heemskerk, Oliver Soehnlein, Christian Weber and Esther Lutgens
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:A178, originally published October 20, 2015

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    Abstract 178: Platelet Cd40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes
    Dirk Lievens, Tom Seijkens, Marijke J Kuijpers, Holger Winkels, Helene Hartwig, Linda Beckers, Remco T Megens, Louis Boon, Randolph J Noelle, Norbert Gerdes, Johan W Heemskerk, Oliver Soehnlein, Christian Weber and Esther Lutgens
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:A178, originally published October 20, 2015
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