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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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2011/432080 |
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| author | Qianxing Zhou Florian Bea Michael Preusch Hongjie Wang Berend Isermann Khurrum Shahzad Hugo A. Katus Erwin Blessing |
| author_facet | Qianxing Zhou Florian Bea Michael Preusch Hongjie Wang Berend Isermann Khurrum Shahzad Hugo A. Katus Erwin Blessing |
| author_sort | Qianxing Zhou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7faae85d3ccb40d5a657ac6e76ab8a66 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-7faae85d3ccb40d5a657ac6e76ab8a662025-02-03T01:26:20ZengWileyMediators of Inflammation0962-93511466-18612011-01-01201110.1155/2011/432080432080Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor RivaroxabanQianxing Zhou0Florian Bea1Michael Preusch2Hongjie Wang3Berend Isermann4Khurrum Shahzad5Hugo A. Katus6Erwin Blessing7Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine I, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine I, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, GermanyAim. 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.http://dx.doi.org/10.1155/2011/432080 |
| spellingShingle | Qianxing Zhou Florian Bea Michael Preusch Hongjie Wang Berend Isermann Khurrum Shahzad Hugo A. Katus Erwin Blessing Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban Mediators of Inflammation |
| title | Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban |
| title_full | Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban |
| title_fullStr | Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban |
| title_full_unstemmed | Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban |
| title_short | Evaluation of Plaque Stability of Advanced Atherosclerotic Lesions in Apo E-Deficient Mice after Treatment with the Oral Factor Xa Inhibitor Rivaroxaban |
| title_sort | evaluation of plaque stability of advanced atherosclerotic lesions in apo e deficient mice after treatment with the oral factor xa inhibitor rivaroxaban |
| url | http://dx.doi.org/10.1155/2011/432080 |
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