RESUMO
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.
Assuntos
Aspirina/farmacologia , Artérias Carótidas/efeitos dos fármacos , Inibidores do Fator Xa/farmacologia , Rivaroxabana/farmacologia , Trombose/tratamento farmacológico , Animais , Artérias/efeitos dos fármacos , Plaquetas/metabolismo , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/tratamento farmacológico , Espessura Intima-Media Carotídea , Leucócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/metabolismo , Trombose/fisiopatologiaRESUMO
The potential relevance of murine atherothrombosis models for understanding human disease has been debated in the past. Despite this, in the last decade, many thrombosis studies with atherogenic Apoe(-/-) mice have been performed, which provide novel insight into the molecular mechanisms by which platelet and coagulation processes accomplish acute thrombus formation after plaque disruption in vivo. Support for these mechanisms has come from whole blood flow perfusion studies over plaque material in vitro, which are also reviewed in this study. The main plaque-derived triggers for thrombus formation appear to be collagen and tissue factor, next to bioactive mediators such as prostaglandin E2. The atherothrombotic process relies on collagen- and ADP-receptor-induced platelet activation as well as on thrombin/fibrin generation via the extrinsic and intrinsic coagulation pathways. Less is known of the persistent effects of a thrombus on atherosclerosis progression, but evidence suggests roles herein of activated platelets and ongoing thrombin generation.