Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery

T. G. Mastenbroek; M. F. A. Karel; M. Nagy; W. Chayoua; E. I. J. Korsten; D. M. Coenen; J. Debets; J. Konings; A. E. Brouns; P. J. A. Leenders; H. van Essen; R. van Oerle; S. Heitmeier; H. M. Spronk; M. J. E. Kuijpers; J. M. E. M. Cosemans

doi:10.1038/s41598-020-76377-8

Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery

T. G. Mastenbroek, M. F. A. Karel, M. Nagy, W. Chayoua, E. I. J. Korsten, D. M. Coenen, J. Debets, J. Konings, A. E. Brouns, P. J. A. Leenders, H. van Essen, R. van Oerle, S. Heitmeier, H. M. Spronk, M. J. E. Kuijpers, J. M. E. M. Cosemans^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

While in recent trials the dual pathway inhibition with aspirin plus rivaroxaban has shown to be efficacious in patients with atherosclerotic cardiovascular disease, little is known about the effects of this combination treatment on thrombus formation and vascular remodelling upon vascular damage. The aim of this study was to examine the effects of aspirin and/or rivaroxaban on injury-induced murine arterial thrombus formation in vivo and in vitro, vessel-wall remodelling, and platelet-leukocyte aggregates. Temporary ligation of the carotid artery of C57BL/6 mice, fed a western type diet, led to endothelial denudation and sub-occlusive thrombus formation. At the site of ligation, the vessel wall stiffened and the intima-media thickened. Aspirin treatment antagonized vascular stiffening and rivaroxaban treatment led to a positive trend towards reduced stiffening. Local intima-media thickening was antagonized by both aspirin or rivaroxaban treatment. Platelet-leukocyte aggregates and the number of platelets per leukocyte were reduced in aspirin and/or rivaroxaban treatment groups. Furthermore, rivaroxaban restricted thrombus growth and height in vitro. In sum, this study shows vascular protective effects of aspirin and rivaroxaban, upon vascular injury of the mouse artery.

Original language	English
Article number	19360
Number of pages	14
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-76377-8
Publication status	Published - 9 Nov 2020

Keywords

P-SELECTIN EXPRESSION
PLATELET-LEUKOCYTE INTERACTIONS
THROMBUS FORMATION
WHOLE-BLOOD
CORONARY
STIFFNESS
COAGULATION
CLOPIDOGREL
ANTIPLATELET
RECRUITMENT

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Mastenbroek, T. G., Karel, M. F. A., Nagy, M., Chayoua, W., Korsten, E. I. J., Coenen, D. M., Debets, J., Konings, J., Brouns, A. E., Leenders, P. J. A., van Essen, H., van Oerle, R., Heitmeier, S., Spronk, H. M., Kuijpers, M. J. E., & Cosemans, J. M. E. M. (2020). Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery. Scientific Reports, 10(1), Article 19360. https://doi.org/10.1038/s41598-020-76377-8

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title = "Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery",

abstract = "While in recent trials the dual pathway inhibition with aspirin plus rivaroxaban has shown to be efficacious in patients with atherosclerotic cardiovascular disease, little is known about the effects of this combination treatment on thrombus formation and vascular remodelling upon vascular damage. The aim of this study was to examine the effects of aspirin and/or rivaroxaban on injury-induced murine arterial thrombus formation in vivo and in vitro, vessel-wall remodelling, and platelet-leukocyte aggregates. Temporary ligation of the carotid artery of C57BL/6 mice, fed a western type diet, led to endothelial denudation and sub-occlusive thrombus formation. At the site of ligation, the vessel wall stiffened and the intima-media thickened. Aspirin treatment antagonized vascular stiffening and rivaroxaban treatment led to a positive trend towards reduced stiffening. Local intima-media thickening was antagonized by both aspirin or rivaroxaban treatment. Platelet-leukocyte aggregates and the number of platelets per leukocyte were reduced in aspirin and/or rivaroxaban treatment groups. Furthermore, rivaroxaban restricted thrombus growth and height in vitro. In sum, this study shows vascular protective effects of aspirin and rivaroxaban, upon vascular injury of the mouse artery.",

keywords = "P-SELECTIN EXPRESSION, PLATELET-LEUKOCYTE INTERACTIONS, THROMBUS FORMATION, WHOLE-BLOOD, CORONARY, STIFFNESS, COAGULATION, CLOPIDOGREL, ANTIPLATELET, RECRUITMENT",

author = "Mastenbroek, {T. G.} and Karel, {M. F. A.} and M. Nagy and W. Chayoua and Korsten, {E. I. J.} and Coenen, {D. M.} and J. Debets and J. Konings and Brouns, {A. E.} and Leenders, {P. J. A.} and {van Essen}, H. and {van Oerle}, R. and S. Heitmeier and Spronk, {H. M.} and Kuijpers, {M. J. E.} and Cosemans, {J. M. E. M.}",

note = "Funding Information: This study was supported by research funding from the Dutch Heart Foundation, Den Haag, the Netherlands (2015T079 to T.G.M., D.M.C. and J.M.E.M.C.) and the Netherlands Organization for Scientific Research (NWO), Den Haag, the Netherlands (Vidi 91716421 M.F.A.K. and J.M.E.M.C.). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = nov,

day = "9",

doi = "10.1038/s41598-020-76377-8",

language = "English",

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Mastenbroek, TG, Karel, MFA, Nagy, M, Chayoua, W, Korsten, EIJ, Coenen, DM, Debets, J, Konings, J, Brouns, AE, Leenders, PJA , van Essen, H , van Oerle, R, Heitmeier, S, Spronk, HM , Kuijpers, MJE & Cosemans, JMEM 2020, 'Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery', Scientific Reports, vol. 10, no. 1, 19360. https://doi.org/10.1038/s41598-020-76377-8

TY - JOUR

T1 - Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery

AU - Mastenbroek, T. G.

AU - Karel, M. F. A.

AU - Nagy, M.

AU - Chayoua, W.

AU - Korsten, E. I. J.

AU - Coenen, D. M.

AU - Debets, J.

AU - Konings, J.

AU - Brouns, A. E.

AU - Leenders, P. J. A.

AU - van Essen, H.

AU - van Oerle, R.

AU - Heitmeier, S.

AU - Spronk, H. M.

AU - Kuijpers, M. J. E.

AU - Cosemans, J. M. E. M.

N1 - Funding Information: This study was supported by research funding from the Dutch Heart Foundation, Den Haag, the Netherlands (2015T079 to T.G.M., D.M.C. and J.M.E.M.C.) and the Netherlands Organization for Scientific Research (NWO), Den Haag, the Netherlands (Vidi 91716421 M.F.A.K. and J.M.E.M.C.). Publisher Copyright: © 2020, The Author(s).

PY - 2020/11/9

Y1 - 2020/11/9

N2 - While in recent trials the dual pathway inhibition with aspirin plus rivaroxaban has shown to be efficacious in patients with atherosclerotic cardiovascular disease, little is known about the effects of this combination treatment on thrombus formation and vascular remodelling upon vascular damage. The aim of this study was to examine the effects of aspirin and/or rivaroxaban on injury-induced murine arterial thrombus formation in vivo and in vitro, vessel-wall remodelling, and platelet-leukocyte aggregates. Temporary ligation of the carotid artery of C57BL/6 mice, fed a western type diet, led to endothelial denudation and sub-occlusive thrombus formation. At the site of ligation, the vessel wall stiffened and the intima-media thickened. Aspirin treatment antagonized vascular stiffening and rivaroxaban treatment led to a positive trend towards reduced stiffening. Local intima-media thickening was antagonized by both aspirin or rivaroxaban treatment. Platelet-leukocyte aggregates and the number of platelets per leukocyte were reduced in aspirin and/or rivaroxaban treatment groups. Furthermore, rivaroxaban restricted thrombus growth and height in vitro. In sum, this study shows vascular protective effects of aspirin and rivaroxaban, upon vascular injury of the mouse artery.

AB - While in recent trials the dual pathway inhibition with aspirin plus rivaroxaban has shown to be efficacious in patients with atherosclerotic cardiovascular disease, little is known about the effects of this combination treatment on thrombus formation and vascular remodelling upon vascular damage. The aim of this study was to examine the effects of aspirin and/or rivaroxaban on injury-induced murine arterial thrombus formation in vivo and in vitro, vessel-wall remodelling, and platelet-leukocyte aggregates. Temporary ligation of the carotid artery of C57BL/6 mice, fed a western type diet, led to endothelial denudation and sub-occlusive thrombus formation. At the site of ligation, the vessel wall stiffened and the intima-media thickened. Aspirin treatment antagonized vascular stiffening and rivaroxaban treatment led to a positive trend towards reduced stiffening. Local intima-media thickening was antagonized by both aspirin or rivaroxaban treatment. Platelet-leukocyte aggregates and the number of platelets per leukocyte were reduced in aspirin and/or rivaroxaban treatment groups. Furthermore, rivaroxaban restricted thrombus growth and height in vitro. In sum, this study shows vascular protective effects of aspirin and rivaroxaban, upon vascular injury of the mouse artery.

KW - P-SELECTIN EXPRESSION

KW - PLATELET-LEUKOCYTE INTERACTIONS

KW - THROMBUS FORMATION

KW - WHOLE-BLOOD

KW - CORONARY

KW - STIFFNESS

KW - COAGULATION

KW - CLOPIDOGREL

KW - ANTIPLATELET

KW - RECRUITMENT

U2 - 10.1038/s41598-020-76377-8

DO - 10.1038/s41598-020-76377-8

M3 - Article

C2 - 33168914

SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 19360

ER -