Evaluation of plaque stability of advanced atherosclerotic lesions in apo E-deficient mice after treatment with the oral factor Xa inhibitor rivaroxaban
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 hypothesi...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
07 Jun 2011
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| In: |
Mediators of inflammation
Year: 2011, Pages: 1-9 |
| ISSN: | 1466-1861 |
| DOI: | 10.1155/2011/432080 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1155/2011/432080 Verlag, lizenzpflichtig, Volltext: https://www.hindawi.com/journals/mi/2011/432080/ 
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| Author Notes: | Qianxing Zhou, Florian Bea, Michael Preusch, Hongjie Wang, Berend Isermann, Khurrum Shahzad, Hugo A. Katus, and Erwin Blessing |
| Summary: | 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. |
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| Item Description: | Gesehen am 19.01.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1466-1861 |
| DOI: | 10.1155/2011/432080 |