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首页> 外文期刊>Journal of Cellular Physiology >Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells
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Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells

机译:从先进的心脏衰竭患者血清促进血管生成和影响Notch通路在人类内皮细胞

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摘要

It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4. We found a higher number of closed tubes in HUVECs treated with advanced HF patients serum in comparison with cells treated with serum from mild HF patients or controls. Furthermore, as indicated by the reduction of the active form of Notch4 (N4IC) and of Jagged1, advanced HF patients serum inhibited Notch signalling in HUVECs in comparison with mild HF patients' serum and controls. The circulating levels of NT-proBNP (N-terminal of the pro-hormone brain natriuretic peptide), a marker for the detection and evalutation of HF, were positively correlated with the number of closed tubes (r = 0.485) and negatively with Notch4IC and Jagged1 levels in sera-treated cells (r = -0.526 and r = -0.604, respectively). In conclusion, we found that sera from advanced HF patients promote sprouting angiogenesis and dysregulate Notch signaling in HUVECs. Our study provides in vitro evidence of an angiogenic stimulus arising during HF progression and suggests a role for the Notch pathway in it. (C) 2016 Wiley Periodicals, Inc.
机译:未知组件是否存在于心失败(高频)患者的血清提供一个血管生成刺激。心力衰竭患者血清是否会影响血管生成及其主要的调制器,切口人类脐静脉内皮细胞通路,细胞(HUVECs)。健康受试者或从患者在不同的高频我们确定阶段:(1)发芽血管生成,通过测量细胞网络(封闭管)胶原蛋白凝胶。受体1、2、4和配体Jagged1,Delta-like4。管HUVECs治疗晚期心力衰竭患者血清相比,细胞治疗血清从轻度心力衰竭患者或控制。的活性形式的减少新的高度(N4IC) Jagged1,先进的高频病人血清抑制切口信号HUVECs相比,轻度心衰病人的血清和控制。(氨基端pro-hormone脑利钠肽),检测和标记进行分析的高频,呈正相关的管(r = 0.485)和关闭消极Notch4IC和Jagged1水平sera-treated细胞(r = -0.526和r = -0.604,分别)。从晚期心力衰竭患者促进发芽就是说,血管生成和切口控制信号HUVECs。在高频血管生成刺激引起进展,并建议一个角色等级通路。

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