Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction.
Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction.
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DOI：
10.3389/fphys.2017.00666
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发表时间：
2017
影响因子：
4
通讯作者：
Carracedo J
中科院分区：
文献类型：
--
作者：
Carmona A;Guerrero F;Buendia P;Obrero T;Aljama P;Carracedo J
心血管疾病是慢性肾病患者死亡的主要原因。硫酸吲哚酚（IS）是一种典型的蛋白质结合尿毒症毒素，常规透析无法有效清除。 IS 增加与慢性肾脏疾病的进展和心血管疾病的发展相关。 IS 激活内皮细胞后，细胞会释放内皮微泡 (EMV)，从而诱导内皮功能障碍。我们开发了 IS 介导的内皮损伤的体外模型，以评估 EMV 对内皮祖细胞 (EPC) 产生的内皮修复过程的功能影响。通过超速离心分离源自 IS 处理的内皮细胞的 EMV，并表征 miRNA 含量。研究了 EMV 对培养中的健康 EPC 的影响。我们观察到 IS 激活内皮细胞，生成的微泡 (IsEMV) 可以调节祖细胞作为集落形成单位的经典内皮作用，并在体外形成新血管。此外，IsEMV 中含有 23 种 miRNA，其中 4 种（miR-181a-5p、miR-4454、miR-150-5p 和 hsa-let-7i-5p）与对照内皮微泡相比在 IsEMV 中表达上调。其他作者发现 miR-181a-5p、miR-4454 和 miR-150-5p 参与促进炎症、细胞凋亡和细胞衰老。有趣的是，我们观察到用 IsEMV 处理的 EPC 中 NFκB 和 p53 增加，而 IκBα 减少。我们的数据表明，IS 能够诱导具有不同膜特征、miRNA 和其他分子的内皮囊泡形成，这使得 EPC 的血管稳态维持不能完全发挥作用。 EMV 的这些特定特征可用作血管疾病诊断和预后的新型生物标志物。
Cardiovascular disease is a major cause of mortality in chronic kidney disease patients. Indoxyl sulfate (IS) is a typical protein-bound uremic toxin that cannot be effectively cleared by conventional dialysis. Increased IS is associated with the progression of chronic kidney disease and development of cardiovascular disease. After endothelial activation by IS, cells release endothelial microvesicles (EMV) that can induce endothelial dysfunction. We developed an in vitro model of endothelial damage mediated by IS to evaluate the functional effect of EMV on the endothelial repair process developed by endothelial progenitor cells (EPCs). EMV derived from IS-treated endothelial cells were isolated by ultracentrifugation and characterized for miRNAs content. The effects of EMV on healthy EPCs in culture were studied. We observed that IS activates endothelial cells and the generated microvesicles (IsEMV) can modulate the classic endothelial roles of progenitor cells as colony forming units and form new vessels in vitro. Moreover, 23 miRNAs were contained in IsEMV including four (miR-181a-5p, miR-4454, miR-150-5p, and hsa-let-7i-5p) that were upregulated in IsEMV compared with control endothelial microvesicles. Other authors have found that miR-181a-5p, miR-4454, and miR-150-5p are involved in promoting inflammation, apoptosis, and cellular senescence. Interestingly, we observed an increase in NFκB and p53, and a decrease in IκBα in EPCs treated with IsEMV. Our data suggest that IS is capable of inducing endothelial vesiculation with different membrane characteristics, miRNAs and other molecules, which makes maintaining of vascular homeostasis of EPCs not fully functional. These specific characteristics of EMV could be used as novel biomarkers for diagnosis and prognosis of vascular disease.
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影响因子：
30.5
作者：
Agudo, Judith;Ruzo, Albert;Tung, Navpreet;Salmon, Helene;Leboeuf, Marylene;Hashimoto, Daigo;Becker, Christian;Garrett-Sinha, Lee-Ann;Baccarini, Alessia;Merad, Miriam;Brown, Brian D.
通讯作者：
Brown, Brian D.
影响因子：
20.1
作者：
Friedrich, EB;Walenta, K;Werner, N
通讯作者：
Werner, N
影响因子：
6.1
作者：
Adijiang, Ayinuer;Goto, Sumie;Niwa, Toshimitsu
通讯作者：
Niwa, Toshimitsu
影响因子：
--
作者：
Izuta H;Shimazawa M;Tsuruma K;Araki Y;Mishima S;Hara H
通讯作者：
Hara H
吲哚尿毒症溶质通过磷脂酰丝氨酸暴露和微粒释放增强红细胞的促凝血活性
影响因子：
4.2
作者：
Gao C;Ji S;Dong W;Qi Y;Song W;Cui D;Shi J
通讯作者：
Shi J