What question did this study set out to answer?

This research investigates whether rivaroxaban can enhance the stability of atherosclerotic plaques in mice deficient in apolipoprotein E.

January 1, 2011Mediators of Inflammation125 citationsOpen Access

Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban

QZQianxing ZhouFudan University FBFlorian BeaHeidelberg University MPMichael R. PreuschHeidelberg University

Key Points

This research investigates whether rivaroxaban can enhance the stability of atherosclerotic plaques in mice deficient in apolipoprotein E.
Apolipoprotein E-deficient mice received rivaroxaban (1 or 5 mg/kg) or standard chow for 26 weeks (n=20 per group).

Structured PICO

Does rivaroxaban attenuate plaque progression and promote stability of advanced atherosclerotic lesions in apolipoprotein E-deficient mice?

Population

Apolipoprotein E-deficient mice with already established atherosclerotic lesions (n=20 per group)

Intervention

Rivaroxaban (1 or 5 mg/kg body weight/day) administered for 26 weeks

Comparator

Standard chow diet

Outcome

Plaque progression and stability of advanced atherosclerotic lesionssurrogate

In a mouse model of advanced atherosclerosis, chronic administration of rivaroxaban promoted plaque stability and reduced inflammation without significantly affecting lesion progression.

Abstract

AIM: Thrombin not only plays a central role in thrombus formation and platelet activation, but also in induction of inflammatory processes. Activated factor X (FXa) is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. We assessed the hypothesis that rivaroxaban, a direct FXa inhibitor, attenuates plaque progression and promotes stability of advanced atherosclerotic lesions in an in vivo model. METHODS AND RESULTS: Rivaroxaban (1 or 5 mg/kg body weight/day) or standard chow diet was administered for 26 weeks to apolipoprotein E-deficient mice (n = 20 per group) with already established atherosclerotic lesions. There was a nonsignificant reduction of lesion progression in the high-concentration group, compared to control mice. FXa inhibition with 5 mg Rivaroxaban/kg/day resulted in increased thickness of the protective fibrous caps (12.3 ± 3.8 μm versus 10.1 ± 2.7 μm; P < .05), as well as in fewer medial erosions and fewer lateral xanthomas, indicating plaque stabilizing properties. Real time-PCR from thoracic aortas revealed that rivaroxaban (5 mg/kg/day) treatment reduced mRNA expression of inflammatory mediators, such of IL-6, TNF-α, MCP-1, and Egr-1 (P < .05). CONCLUSIONS: Chronic administration of rivaroxaban does not affect lesion progression but downregulates expression of inflammatory mediators and promotes lesion stability in apolipoprotein E-deficient mice.

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