PDF(Pubmed)
Abstract：
Direct Oral Anticoagulants (DOACs) have simplified the treatment of thromboembolic disease. In addition to their established anticoagulant effects, there are indications from clinical and preclinical studies that DOACs exhibit also non-anticoagulant actions, such as anti-inflammatory and anti-oxidant actions, advocating overall cardiovascular protection. In the present study, we provide a comprehensive overview of the existing knowledge on the pleiotropic effects of DOACs on endothelial cells (ECs) in vitro and their underlying mechanisms, while also identifying potential differences among DOACs. DOACs exhibit pleiotropic actions on ECs, such as anti-inflammatory, anti-atherosclerotic, and anti-fibrotic effects, as well as preservation of endothelial integrity. These effects appear to be mediated through inhibition of the proteinase-activated receptor signaling pathway. Furthermore, we discuss the potential differences among the four drugs in this class. Further research is needed to fully understand the pleiotropic effects of DOACs on ECs, their underlying mechanisms, as well as the heterogeneity between various DOACs. Such studies can pave the way for identifying biomarkers that can help personalize pharmacotherapy with this valuable class of drugs.
摘要：
直接口服抗凝剂（DOAC）简化了血栓栓塞性疾病的治疗。除了其既定的抗凝作用，有迹象表明，从临床和临床前研究，DOAC也表现出非抗凝作用，如抗炎和抗氧化作用，提倡全面的心血管保护。在本研究中,我们提供了关于DOAC在体外对内皮细胞（ECs）的多效性作用及其潜在机制的现有知识的全面概述，同时还确定DOAC之间的潜在差异。DOAC对EC表现出多效性作用，如抗炎，抗动脉粥样硬化，和抗纤维化作用，以及保存内皮完整性。这些作用似乎是通过抑制蛋白酶激活的受体信号传导途径介导的。此外，我们讨论了这四种药物之间的潜在差异。需要进一步的研究来充分了解DOAC对EC的多效性作用，它们的潜在机制，以及各种DOAC之间的异质性。这样的研究可以为识别生物标志物铺平道路，这些生物标志物可以帮助使用这种有价值的药物进行个性化的药物治疗。
