Rivaroxaban, a Direct Oral Factor Xa Inhibitor, Attenuates Atherosclerosis by Alleviating Factor Xa–PAR2-Mediated Autophagy Suppression
Yusuke Ito, Yasuhiro Maejima, Shun Nakagama, Yuka Shiheido‐Watanabe, Natsuko Tamura, Tetsuo Sasano
Abstract
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.