Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy.
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Via dell'Istria 65/01, 34137 Trieste, Italy.
Mediators Inflamm. 2013;2013:423407. doi: 10.1155/2013/423407. Epub 2013 Dec 31.
Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n = 31) in CVD patients' plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF- α2, G-CSF, MIP-1β, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that αLipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.
大静脉内皮在慢性静脉疾病（CVD）和血栓形成等临床疾病中发挥重要作用；因此，对 CVD 血管内皮细胞（VEC）进行特征分析对于确定特定的治疗靶点具有战略意义。在此基础上，我们评估了天然抗炎化合物α-硫辛酸和银杏叶提取物对 CVD 患者来源的 VEC 释放的细胞因子/趋化因子的影响。为此，我们比较了 CVD 患者血浆与健康对照者的细胞因子/趋化因子（n=31）谱，并对从同一患者中纯化的 VEC 在未刺激和 TNF-α刺激条件下的细胞因子/趋化因子释放情况进行了特征分析。在 VEC 释放的细胞因子/趋化因子中，我们鉴定了那些与全身特征（IL-8、TNF-α、GM-CSF、INF-α2、G-CSF、MIP-1β、VEGF、EGF、Eotaxin、MCP-1、CXCL10、PDGF 和 RANTES）相吻合的细胞因子/趋化因子，并确定了这些细胞因子/趋化因子可以通过α-硫辛酸和/或银杏叶提取物进行离体处理（GM-CSF、G-CSF、CXCL10、PDGF 和 RANTES）。最后，通过研究涉及促进细胞因子/趋化因子释放的细胞内途径，这些途径是天然抗炎化合物的靶点，我们记录到α-硫辛酸显著抑制了 TNF-α诱导的 NF-κB 和 p38/MAPK 激活，而银杏叶的作用似乎主要是通过 Akt 介导的。我们的数据为 CVD 发病机制的分子机制提供了新的见解，突出了新的潜在治疗靶点。
