Fredman Gabrielle, Tabas Ira
Department of Molecular and Cellular Physiology, Center for Cardiovascular Sciences, Albany Medical College, Albany, New York.
Departments of Medicine, Pathology and Cell Biology, and Physiology, Columbia University Medical Center, New York, New York.
Am J Pathol. 2017 Jun;187(6):1211-1221. doi: 10.1016/j.ajpath.2017.01.018.
Defective inflammation resolution is the underlying cause of prevalent chronic inflammatory diseases, such as arthritis, asthma, cancer, and neurodegenerative and cardiovascular diseases. Inflammation resolution is governed by several endogenous factors, including fatty acid-derived specialized proresolving mediators and proteins, such as annexin A1. Specifically, specialized proresolving mediators comprise a family of mediators that include arachidonic acid-derived lipoxins, omega-3 fatty acid eicosapentaenoic acid-derived resolvins, docosahexaenoic acid-derived resolvins, protectins, and maresins. Emerging evidence indicates that imbalances between specialized proresolving mediators and proinflammatory mediators are associated with several prevalent human diseases, including atherosclerosis. Mechanisms that drive this imbalance remain largely unknown and will be discussed in this review. Furthermore, the concept of dysregulated inflammation resolution in atherosclerosis has been known for several decades. Recently, there has been an explosion of new work with regard to the therapeutic application of proresolving ligands in experimental atherosclerosis. Therefore, this review will highlight recent advances in our understanding of how inflammation resolution may become defective in atherosclerosis and the potential for proresolving therapeutics in atherosclerosis. Last, we offer insight for future implications of the field.
炎症消退功能缺陷是常见慢性炎症性疾病的根本原因，如关节炎、哮喘、癌症以及神经退行性疾病和心血管疾病。炎症的消退受多种内源性因素调控，包括脂肪酸衍生的特异性促消退介质和蛋白质，如膜联蛋白A1。具体而言，特异性促消退介质包括一类介质，其中有花生四烯酸衍生的脂氧素、ω-3脂肪酸二十碳五烯酸衍生的消退素、二十二碳六烯酸衍生的消退素、保护素和maresin。新出现的证据表明，特异性促消退介质与促炎介质之间的失衡与包括动脉粥样硬化在内的几种常见人类疾病有关。导致这种失衡的机制在很大程度上仍不清楚，本文将对此进行讨论。此外，动脉粥样硬化中炎症消退失调的概念已为人所知数十年。最近，关于促消退配体在实验性动脉粥样硬化治疗应用方面的新研究激增。因此，本文将重点介绍我们对动脉粥样硬化中炎症消退如何出现缺陷以及促消退疗法在动脉粥样硬化中的潜力的最新认识。最后，我们对该领域的未来发展方向提出见解。
