Resolution of vascular injury: Specialized lipid mediators and their evolving therapeutic implications.
Resolution of vascular injury: Specialized lipid mediators and their evolving therapeutic implications.
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DOI：
10.1016/j.mam.2017.07.005
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发表时间：
2017-12
影响因子：
10.6
通讯作者：
Conte MS
中科院分区：
文献类型：
--
作者：
Wu B;Mottola G;Schaller M;Upchurch GR Jr;Conte MS
急性血管损伤发生在许多重要的临床环境中，包括自发的疾病相关事件（如斑块破裂、血栓形成）和治疗干预，如血管成形术、支架植入或搭桥手术。内皮细胞（EC）破坏暴露底层基质，导致血小板、凝血蛋白和白细胞的快速沉积。随后，以白细胞募集、血管平滑肌细胞（VSMC）激活、细胞因子、活性氧和血管壁内生长因子的细化为特征的血栓炎症反应。血管损伤的消退期可以描述为发生白细胞外排、碎片清除和再内皮化。VSMC的迁移和增殖导致增厚的新内膜的发展，这可能导致管腔损伤。随后的重塑包括基质蛋白沉积，以及EC和VSMC恢复到静止状态。最近的研究表明，专门的促脂质介质（SPM）调节了这一反应的关键方面，并可能在脉管系统中构成内源性稳态途径。SPM直接作用于血管细胞，可抑制炎症信号，减少白细胞粘附，抑制VSMC的迁移和增殖。这些影响似乎主要依赖于g蛋白偶联受体。在一系列血管损伤动物模型中，包括球囊血管成形术、旁路移植术和实验性动脉瘤形成，SPM加速修复并减少病变形成。SPM具有pM-nM范围内的生物活性，缺乏可识别的细胞毒性，以及一系列血管保护特性，代表了一类新的血管治疗药物。本文综述了该领域的研究现状，包括对翻译的关键下一步和挑战的考虑。
Acute vascular injury occurs in a number of important clinical contexts, including spontaneous disease-related events (e.g. plaque rupture, thrombosis) and therapeutic interventions such as angioplasty, stenting, or bypass surgery. Endothelial cell (EC) disruption exposes the underlying matrix, leading to a rapid deposition of platelets, coagulation proteins, and leukocytes. A thrombo-inflammatory response ensues characterized by leukocyte recruitment, vascular smooth muscle cell (VSMC) activation, and the elaboration of cytokines, reactive oxygen species and growth factors within the vessel wall. A resolution phase of vascular injury may be described in which leukocyte efflux, clearance of debris, and re-endothelialization occurs. VSMC migration and proliferation leads to the development of a thickened neointima that may lead to lumen compromise. Subsequent remodeling involves matrix protein deposition, and return of EC and VSMC to quiescence. Recent studies suggest that specialized proresolving lipid mediators (SPM) modulate key aspects of this response, and may constitute an endogenous homeostatic pathway in the vasculature. SPM exert direct effects on vascular cells that counteract inflammatory signals, reduce leukocyte adhesion, and inhibit VSMC migration and proliferation. These effects appear to be largely G-protein coupled receptor-dependent. Across a range of animal models of vascular injury, including balloon angioplasty, bypass grafting, and experimental aneurysm formation, SPM accelerate repair and reduce lesion formation. With bioactivity in the pM-nM range, a lack of discernible cytotoxicity, and a spectrum of vasculo-protective properties, SPM represent a novel class of vascular therapeutics. This review summarizes current research in this field, including a consideration of critical next steps and challenges in translation.
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DOI：
10.1084/jem.20132011
发表时间：
2014-07-28
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Endo J;Sano M;Isobe Y;Fukuda K;Kang JX;Arai H;Arita M
通讯作者：
Arita M
影响因子：
20.3
作者：
Brancaleone, Vincenzo;Gobbetti, Thomas;Perretti, Mauro
通讯作者：
Perretti, Mauro
影响因子：
37.8
作者：
BREZINSKI, DA;NESTO, RW;SERHAN, CN
通讯作者：
SERHAN, CN
影响因子：
16.6
作者：
Fredman, Gabrielle;Hellmann, Jason;Proto, Jonathan D.;Kuriakose, George;Colas, Romain A.;Dorweiler, Bernhard;Connolly, E. Sander;Solomon, Robert;Jones, David M.;Heyer, Eric J.;Spite, Matthew;Tabas, Ira
通讯作者：
Tabas, Ira
影响因子：
4.8
作者：
Boergeson, Emma;Docherty, Neil G.;Godson, Catherine
通讯作者：
Godson, Catherine