Journal
JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 6, Issue 12, Pages 964-980Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2021.09.010
Keywords
atherosclerosis; autophagy; factor Xa; inflammasome; rivaroxaban
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Funding
- Bayer Yakuhin Ltd
- JSPS KAKENHI [17K09570]
- AstraZeneca
- Boehringer Ingelheim
- Bayer
- Bristol-Myers Squibb
- Chugai Pharmaceuticals
- Eli Lilly
- MSD
- Novartis Pharma
- Grants-in-Aid for Scientific Research [17K09570] Funding Source: KAKEN
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The authors demonstrated a mechanism for attenuating atherosclerosis by administering an oral factor Xa inhibitor, RIV. This attenuation was achieved by suppressing macrophage autophagy and abrogating inflammasome activity.
The authors showed a mechanism for attenuating atherosclerosis by directly administering an oral factor Xa inhibitor (ie, rivaroxaban [RIV]). The autophagy activity of macrophages was significantly suppressed by factor Xa and was alleviated by the administration of RIV. However, factor Xa failed to inhibit 7-ketocholesterol-induced autophagy and inflammasome activation in protease-activated receptor 2 (PAR2) knockout macrophages. The atherosclerotic area of apolipoprotein E knockout mice was significantly reduced by the genetic ablation of PAR2, which was partially reversed by chloroquine. Thus, the authors found that RIV attenuates atherogenesis by inhibiting the factor Xa-PAR2-mediated suppression of macrophage autophagy and abrogating inflammasome activity. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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