Sansbury Brian E, Spite Matthew
From the Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Circ Res. 2016 Jun 24;119(1):113-30. doi: 10.1161/CIRCRESAHA.116.307308.
Acute inflammation is a host-protective response that is mounted in response to tissue injury and infection. Initiated and perpetuated by exogenous and endogenous mediators, acute inflammation must be resolved for tissue repair to proceed and for homeostasis to be restored. Resolution of inflammation is an actively regulated process governed by an array of mediators as diverse as those that initiate inflammation. Among these, resolvins have emerged as a genus of evolutionarily conserved proresolving mediators that act on specific cellular receptors to regulate leukocyte trafficking and blunt production of inflammatory mediators, while also promoting clearance of dead cells and tissue repair. Given that chronic unresolved inflammation is emerging as a central causative factor in the development of cardiovascular diseases, an understanding of the endogenous processes that govern normal resolution of acute inflammation is critical for determining why sterile maladaptive cardiovascular inflammation perpetuates. Here, we provide an overview of the process of resolution with a focus on the enzymatic biosynthesis and receptor-dependent actions of resolvins and related proresolving mediators in immunity, thrombosis, and vascular biology. We discuss how nutritional and current therapeutic approaches modulate resolution and propose that harnessing resolution concepts could potentially lead to the development of new approaches for treating chronic cardiovascular inflammation in a manner that is not host disruptive.
急性炎症是机体对组织损伤和感染的一种保护性反应。由外源性和内源性介质引发并持续，急性炎症必须得到消退，组织修复才能进行，内环境稳态才能得以恢复。炎症的消退是一个受多种介质积极调控的过程，这些介质与引发炎症的介质一样多样。其中，消退素已成为一类进化上保守的促消退介质，它们作用于特定的细胞受体，调节白细胞的迁移，抑制炎症介质的产生，同时还促进死细胞的清除和组织修复。鉴于慢性未消退炎症正成为心血管疾病发展的核心致病因素，了解调控急性炎症正常消退的内源性过程对于确定无菌性适应性不良心血管炎症持续存在的原因至关重要。在此，我们概述了炎症消退过程，重点关注消退素及相关促消退介质在免疫、血栓形成和血管生物学中的酶促生物合成及受体依赖性作用。我们讨论了营养和当前治疗方法如何调节炎症消退，并提出利用炎症消退的概念可能会开发出以不破坏宿主的方式治疗慢性心血管炎症的新方法。
