Evaluation of plaque stability of advanced atherosclerotic lesions in apo E-deficient mice after treatment with the oral factor Xa inhibitor rivaroxaban

• Verfasst von: Zhou, Qianxing [VerfasserIn]
• Verfasst von: Bea, Florian [VerfasserIn]
• Verfasst von: Preusch, Michael [VerfasserIn]
• Verfasst von: Wang, Hongjie [VerfasserIn]
• Verfasst von: Isermann, Berend [VerfasserIn]
• Verfasst von: Shahzad Hussain, Khurrum [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Blessing, Erwin [VerfasserIn]
• Titel: Evaluation of plaque stability of advanced atherosclerotic lesions in apo E-deficient mice after treatment with the oral factor Xa inhibitor rivaroxaban
• Verf.angabe: Qianxing Zhou, Florian Bea, Michael Preusch, Hongjie Wang, Berend Isermann, Khurrum Shahzad, Hugo A. Katus, and Erwin Blessing
• E-Jahr: 2011
• Jahr: 07 Jun 2011
• Umfang: 9 S.
• Fussnoten: Gesehen am 19.01.2023
• Titel Quelle: Enthalten in: Mediators of inflammation
• Ort Quelle: Sylvania, Ohio : Hindawi Publishing Corp., 1992
• Jahr Quelle: 2011
• Band/Heft Quelle: (2011), Artikel-ID 432080, Seite 1-9
• ISSN Quelle: 1466-1861
• DOI: doi:10.1155/2011/432080
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1831514923

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 ( 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.