Mitchell Jane A, Kirkby Nicholas S, Ahmetaj-Shala Blerina, Armstrong Paul C, Crescente Marilena, Ferreira Plinio, Lopes Pires Maria Elisa, Vaja Ricky, Warner Timothy D
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, SW7 2AZ, United Kingdom.
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, SW7 2AZ, United Kingdom.
Pharmacol Ther. 2021 Jan;217:107624. doi: 10.1016/j.pharmthera.2020.107624. Epub 2020 Jul 5.
Cyclooxygenase (COX)-1 and COX-2 are centrally important enzymes within the cardiovascular system with a range of diverse, sometimes opposing, functions. Through the production of thromboxane, COX in platelets is a pro-thrombotic enzyme. By contrast, through the production of prostacyclin, COX in endothelial cells is antithrombotic and in the kidney regulates renal function and blood pressure. Drug inhibition of COX within the cardiovascular system is important for both therapeutic intervention with low dose aspirin and for the manifestation of side effects caused by nonsteroidal anti-inflammatory drugs. This review focuses on the role that COX enzymes and drugs that act on COX pathways have within the cardiovascular system and provides an in-depth resource covering COX biology and pharmacology. The review goes on to consider the role of COX in both discrete cardiovascular locations and in associated organs that contribute to cardiovascular health. We discuss the importance of, and strategies to manipulate the thromboxane: prostacyclin balance. Finally within this review the authors discuss testable COX-2-hypotheses intended to stimulate debate and facilitate future research and therapeutic opportunities within the field.
环氧化酶（COX）-1和COX-2是心血管系统中至关重要的酶，具有一系列多样的、有时甚至相互对立的功能。血小板中的COX通过生成血栓素，是一种促血栓形成酶。相比之下，内皮细胞中的COX通过生成前列环素，具有抗血栓形成作用，并在肾脏中调节肾功能和血压。心血管系统中对COX的药物抑制对于低剂量阿司匹林的治疗干预以及非甾体抗炎药引起的副作用表现都很重要。本综述重点关注COX酶和作用于COX途径的药物在心血管系统中的作用，并提供了涵盖COX生物学和药理学的深入资源。该综述接着探讨了COX在离散的心血管部位以及对心血管健康有贡献的相关器官中的作用。我们讨论了调节血栓素：前列环素平衡的重要性及策略。最后，在本综述中，作者讨论了可检验的COX-2假说，旨在激发辩论并促进该领域未来的研究和治疗机会。
