Pleiotropic effects of NOACs with focus on edoxaban: scientific findings and potential clinical implications.

Andreas Goette, Martin Mollenhauer, Volker Rudolph, Mathias Lamparter, Martin Meier, Michael Böhm
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Abstract

Non-vitamin K antagonist oral anticoagulants (NOACs) are well-established as inhibitors of factor Xa (FXa) and thrombin in the treatment and prevention of thrombosis. However, there is growing evidence that beneficial outcomes might be based on additional pleiotropic effects beyond anticoagulation. FXa and thrombin are also known to activate protease-activated receptors (PARs), which can mediate pro-inflammatory and pro-fibrotic effects. Since PAR‑1 and PAR‑2 play an important role in the development of atherosclerosis, the inhibition of this pathway represents an interesting potential target for preventing the progression of atherosclerosis and fibrosis. This review focuses on potential pleiotropic effects of FXa inhibition with edoxaban seen in a variety of studies in different in vitro and in vivo test systems. As common findings from these experiments, edoxaban was able to attenuate FXa- and thrombin-induced pro-inflammatory and pro-fibrotic effects and decrease pro-inflammatory cytokine expression. In some, but not all experiments edoxaban was also shown to decrease the levels of PAR‑1 and PAR‑2 expression. Further studies are required to clarify the clinical implications of the pleiotropic effects mediated by NOACs.

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以依多沙班为重点的NOACs的多效效应:科学发现和潜在的临床意义。
非维生素K拮抗剂口服抗凝剂(NOACs)作为Xa因子(FXa)和凝血酶的抑制剂,在治疗和预防血栓形成中得到了广泛的应用。然而,越来越多的证据表明,有益的结果可能是基于抗凝之外的其他多效性作用。已知FXa和凝血酶也能激活蛋白酶激活受体(PARs),从而介导促炎和促纤维化作用。由于PAR - 1和PAR - 2在动脉粥样硬化的发展中起重要作用,抑制这一途径代表了预防动脉粥样硬化和纤维化进展的一个有趣的潜在靶点。这篇综述的重点是在不同的体外和体内试验系统的各种研究中发现的伊多沙班抑制FXa的潜在多效效应。正如这些实验的共同发现,依多沙班能够减弱FXa和凝血酶诱导的促炎和促纤维化作用,并降低促炎细胞因子的表达。在一些(但不是全部)实验中,伊多沙班也显示出PAR‑1和PAR‑2表达水平的降低。需要进一步的研究来阐明NOACs介导的多效效应的临床意义。
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来源期刊
Herzschrittmachertherapie und Elektrophysiologie
Herzschrittmachertherapie und Elektrophysiologie Medicine-Cardiology and Cardiovascular Medicine
CiteScore
1.10
自引率
0.00%
发文量
76
期刊介绍: Mit wissenschaftlichen Original- und Übersichtsarbeiten, Berichten über moderne Operationstechniken und experimentelle Methoden ist die Zeitschrift Herzschrittmachertherapie + Elektrophysiologie ein Diskussionsforum für Themen wie: - Zelluläre Elektrophysiologie - Theoretische Elektrophysiologie - Klinische Elektrophysiologie - Angewandte Herzschrittmachertherapie - Bradykarde und tachykarde Herzrhythmusstörungen - Plötzlicher Herztod und Risikostratifikation - Elektrokardiographie - Elektromedizinische Technologie - Experimentelle und klinische Pharmakologie - Herzchirurgie bei Herzrhythmusstörungen Mitteilungen der Arbeitsgruppen Herzschrittmacher und Arrhythmie der Deutschen Gesellschaft für Kardiologie - Herz und Kreislaufforschung e.V. (DGK) sowie Stellungnahmen und praktische Hinweise runden das breite Spektrum dieser Zeitschrift ab. Interessensgebiete: Kardiologie, Herzschrittmachertherapie, Herzschrittmachertechnologie, klinische Elektrophysiologie
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