Chatterjee Anuran, Komshian Sevan, Sansbury Brian E, Wu Bian, Mottola Giorgio, Chen Mian, Spite Matthew, Conte Michael S
Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
Department of Surgery, University of California San Francisco, San Francisco, California, USA.
FASEB J. 2017 Aug;31(8):3393-3402. doi: 10.1096/fj.201700082R. Epub 2017 Apr 25.
Recent evidence suggests that specialized proresolving lipid mediators (SPMs) generated from docosahexaenoic acid (DHA) can modulate the vascular injury response. However, cellular sources for these autacoids within the vessel wall remain unclear. Here, we investigated whether isolated vascular cells and tissues can produce SPMs and assessed expression and subcellular localization of the key SPM biosynthetic enzyme 5-lipoxygenase (LOX) in vascular cells. Intact human arteries incubated with DHA produced 17-hydroxy DHA (17-HDHA) and D-series resolvins, as assessed by liquid chromatography-tandem mass spectrometry. Addition of 17-HDHA to human arteries similarly increased resolvin production. Primary cultures of human saphenous vein endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) converted 17-HDHA to SPMs, including resolvin D1 (RvD1) and other D-series resolvins and protectins. This was accompanied by a rapid translocation of 5-LOX from nucleus to cytoplasm in both ECs and VSMCs, potentially facilitating SPM biosynthesis. Conditioned medium from cells exposed to 17-HDHA inhibited monocyte adhesion to TNF-α-stimulated EC monolayers. These downstream effects were partially reversed by antibodies against the RvD1 receptors ALX/FPR2 and GPR32. These results suggest that autocrine and/or paracrine signaling locally generated SPMs in the vasculature may represent a novel homeostatic mechanism of relevance to vascular health and disease.-Chatterjee, A., Komshian, S., Sansbury, B. E., Wu, B., Mottola, G., Chen, M., Spite, M., Conte, M. S. Biosynthesis of proresolving lipid mediators by vascular cells and tissues.
最近的证据表明，由二十二碳六烯酸（DHA）产生的特异性促消退脂质介质（SPM）可调节血管损伤反应。然而，血管壁内这些自分泌物质的细胞来源仍不清楚。在此，我们研究了分离的血管细胞和组织是否能产生SPM，并评估了血管细胞中关键的SPM生物合成酶5-脂氧合酶（LOX）的表达和亚细胞定位。通过液相色谱-串联质谱法评估，完整的人动脉与DHA孵育后产生了17-羟基DHA（17-HDHA）和D系列消退素。向人动脉中添加17-HDHA同样增加了消退素的产生。人隐静脉内皮细胞（EC）和平滑肌细胞（VSMC）的原代培养物将17-HDHA转化为SPM，包括消退素D1（RvD1）和其他D系列消退素以及保护素。这伴随着EC和VSMC中5-LOX从细胞核快速转运至细胞质，这可能促进了SPM的生物合成。暴露于17-HDHA的细胞条件培养基可抑制单核细胞对TNF-α刺激的EC单层的黏附。这些下游效应被抗RvD1受体ALX/FPR2和GPR32的抗体部分逆转。这些结果表明，血管系统中局部产生的自分泌和/或旁分泌信号SPM可能代表了一种与血管健康和疾病相关的新型稳态机制。——查特吉，A.，科姆西安，S.，桑斯伯里，B.E.，吴，B.，莫托拉，G.，陈，M.，斯皮特，M.，孔特，M.S.血管细胞和组织中促消退脂质介质的生物合成
