Viola Joana, Soehnlein Oliver
Institute for Cardiovascular Prevention (IPEK), LMU Munich, Germany.
Institute for Cardiovascular Prevention (IPEK), LMU Munich, Germany; Department of Pathology, Academic Medical Center (AMC), Amsterdam, The Netherlands; German Centre for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany.
Semin Immunol. 2015 May;27(3):184-93. doi: 10.1016/j.smim.2015.03.013. Epub 2015 Apr 10.
Atherosclerosis is commonly looked upon as a chronic inflammatory disease of the arterial wall arising from an unbalanced lipid metabolism and a maladaptive inflammatory response. However, atherosclerosis is not merely an inflammation of the vessel wall. In fact, the cardinal signs of unstable atherosclerotic lesions are primarily characteristics of failed resolution of a chronic inflammation. In contrast to acute inflammatory events which are typically self-limiting, atherosclerosis is an unresolved inflammatory condition, lacking the switch from the pro-inflammatory to the pro-resolving phase, the latter characterized by termination of inflammatory cell recruitment, removal of inflammatory cells from the site of inflammation by apoptosis and dead cell clearance, reprogramming of macrophages toward an anti-inflammatory, regenerative phenotype, and finally egress of effector cells and tissue regeneration. Here we present an overview on mechanisms of failed resolution contributing to atheroprogression and deliver a summary of novel therapeutic strategies to restore resolution in inflamed arteries.
动脉粥样硬化通常被视为一种源于脂质代谢失衡和适应性炎症反应失调的动脉壁慢性炎症性疾病。然而，动脉粥样硬化不仅仅是血管壁的炎症。事实上，不稳定动脉粥样硬化病变的主要特征本质上是慢性炎症消退失败的特征。与通常具有自限性的急性炎症事件不同，动脉粥样硬化是一种未解决的炎症状态，缺乏从促炎阶段向促消退阶段的转变，后者的特征是炎症细胞募集终止、通过凋亡从炎症部位清除炎症细胞和清除死亡细胞、将巨噬细胞重新编程为抗炎、再生表型，以及最终效应细胞的流出和组织再生。在此，我们概述了导致动脉粥样硬化进展的消退失败机制，并总结了恢复炎症动脉消退的新型治疗策略。
