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.

Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

“…In mice with temporal carotid artery strangulation treated with ASA, the percentage of PLA were increased in resting samples, and there were no changes after activation compared with placebo. However, in the same conditions, PLA as platelet to leucocyte ratio was decreased both with and without stimulation [ 142 ]. In another ischemia model, with an after-reperfusion effect on intestinal microcirculation in mice, there were less PLA after ASA intake than placebo [ 143 ].…”

Effects of medication intake on the risk of hemorrhage in patients with sporadic cerebral cavernous malformations

“…They block endothelial cofactors that cause an increase in anticoagulant-activated protein C, which may lead to recurrent CCM hemorrhages ( 30 ). Animal experiments have revealed a general vascular protective effect of the two drug groups ( 31 ). In rodent models with rabbit elastase aneurysms, ASA intake prevented inflammation of the periadventitial tissue and vessel wall ( 32 , 33 ).…”

The effect of rivaroxaban low doses on the stable angina of the II–III functional class clinical manifestations and the quality of life in patients with ischemic heart disease

“…Привлекают внимание сосудистые эффекты ривароксабана. В эксперименте подтверждена его способность подавлять образование лейкоцитарно-тромбоцитарных агрегатов [8,18,19] при 2-недельном наблюдении после повреждения сосуда, что может вести к улучшению вязкости крови и тканевого кровотока. Сходные данные были получены при применении ривароксабана в экспериментальной модели цирроза печени, что способствовало снижению риска развития микротромбозов, окислительного стресса, улучшению функции эндотелия [20].…”