Nikiforov Nikita G, Wetzker Reinhard, Kubekina Marina V, Petukhova Anna V, Kirichenko Tatiana V, Orekhov Alexander N
National Medical Research Center of Cardiology, Institute of Experimental Cardiology, Moscow, Russia.
Institute of Gene Biology, Centre of Collective Usage, Moscow, Russia.
Front Pharmacol. 2019 Jun 27;10:725. doi: 10.3389/fphar.2019.00725. eCollection 2019.
Inflammation is one of the key processes in the pathogenesis of atherosclerosis. Numerous studies are focused on the local inflammatory processes associated with atherosclerotic plaque initiation and progression. However, changes in the activation state of circulating monocytes, the main components of the innate immunity, may precede the local events. In this article, we discuss tolerance, which results in decreased ability of monocytes to be activated by pathogens and other stimuli, and training, the ability of monocyte to potentiate the response to pathological stimuli, and their relation to atherosclerosis. We also present previously unpublished results of the experiments that our group performed with monocytes/macrophages isolated from atherosclerosis patients. Our data allow assuming the existence of relationship between the formation of monocyte training and the degree of atherosclerosis progression. The suppression of trained immunity seems to be a perspective model for searching anti-atherogenic drugs.
炎症是动脉粥样硬化发病机制中的关键过程之一。众多研究聚焦于与动脉粥样硬化斑块起始和进展相关的局部炎症过程。然而,作为固有免疫主要成分的循环单核细胞激活状态的改变可能先于局部事件发生。在本文中,我们讨论了耐受性(其导致单核细胞被病原体和其他刺激激活的能力下降)和训练(单核细胞增强对病理刺激反应的能力),以及它们与动脉粥样硬化的关系。我们还展示了我们团队对从动脉粥样硬化患者分离出的单核细胞/巨噬细胞进行实验所得的此前未发表的结果。我们的数据使我们能够推测单核细胞训练的形成与动脉粥样硬化进展程度之间存在关联。抑制训练有素的免疫似乎是寻找抗动脉粥样硬化药物的一个有前景的模型。