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Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target.
Biorheology ( IF 1.0 ) Pub Date : 2019-01-01 , DOI: 10.3233/bir-180205
Ian C Harding 1 , Ronodeep Mitra 2 , Solomon A Mensah 1 , Alina Nersesyan 1 , Nandita N Bal 2 , Eno E Ebong 1, 2, 3
Affiliation  

BACKGROUND The onset of many disease processes depends on the function of the endothelial cell (EC) glycocalyx (GCX) which acts as a flow-dependent barrier to cellular infiltration and molecular transport across the blood vessel wall. OBJECTIVE This review aims to examine these processes with the potential end goal of implementing GCX repair to restore EC barrier function and slow the progression of disease. METHODS Cell and mouse studies were employed to examine the state of EC GCX in healthy versus disruptive flow conditions. Correlations of observations of the GCX with a number of EC functions were sought with an emphasis on studies of trans-endothelial barrier integrity against vessel wall infiltration of cells and molecules from the circulation. To demonstrate the importance of GCX as a regulator of trans-endothelial infiltration, assays were performed using ECs with an intact GCX and compared to assays of ECs with an experimentally degraded GCX. Studies were also conducted of ECs in which a degraded GCX was repaired. RESULTS In healthy flow conditions, the EC GCX was found to be thick and substantially covered the endothelial surface. GCX expression dropped significantly in complex flow conditions and coincided with a disease-like cellular and molecular accumulation in the endothelium or within the blood vessel wall. Therapeutic repair of the GCX abolished this accumulation. CONCLUSIONS Regenerating the degraded GCX reverses EC barrier dysfunction and may attenuate the progression of vascular disease.

中文翻译:

内皮屏障增强依赖于流量调节的糖萼,这是潜在的治疗靶点。

背景技术许多疾病过程的发作取决于内皮细胞(EC)糖萼(GCX)的功能,该内皮糖萼作为细胞渗透和分子跨血管壁运输的流量依赖性屏障。目的这篇综述旨在检查这些过程,最终目的是实施GCX修复以恢复EC屏障功能并减慢疾病的进展。方法采用细胞和小鼠研究检查健康与破坏性流动条件下EC GCX的状态。寻找GCX与许多EC功能的观察结果的相关性,重点是研究跨内皮屏障完整性对血管壁渗透细胞和分子从循环中渗透的研究。为了证明GCX作为跨内皮渗透调节剂的重要性,使用具有完整GCX的EC进行测定,并与使用实验降解的GCX的EC进行比较。还对修复了降解的GCX的EC进行了研究。结果在健康的血流条件下,发现EC GCX较厚且基本覆盖了内皮表面。在复杂的流动条件下,GCX的表达显着下降,并且与内皮或血管壁内的疾病样细胞和分子蓄积相吻合。GCX的治疗性修复消除了这种积累。结论再生降解的GCX可逆转EC屏障功能障碍,并可能减弱血管疾病的进展。还对修复了降解的GCX的EC进行了研究。结果在健康的血流条件下,发现EC GCX较厚且基本覆盖了内皮表面。在复杂的流动条件下,GCX的表达显着下降,并与内皮或血管壁内的疾病样细胞和分子蓄积相吻合。GCX的治疗性修复消除了这种积累。结论再生降解的GCX可逆转EC屏障功能障碍,并可能减弱血管疾病的进展。还对修复了降解的GCX的EC进行了研究。结果在健康的血流条件下,发现EC GCX较厚且基本覆盖了内皮表面。在复杂的流动条件下,GCX的表达显着下降,并且与内皮或血管壁内的疾病样细胞和分子蓄积相吻合。GCX的治疗性修复消除了这种积累。结论再生降解的GCX可逆转EC屏障功能障碍,并可能减缓血管疾病的进展。在复杂的流动条件下,GCX的表达显着下降,并且与内皮或血管壁内的疾病样细胞和分子蓄积相吻合。GCX的治疗性修复消除了这种积累。结论再生降解的GCX可逆转EC屏障功能障碍,并可能减缓血管疾病的进展。在复杂的流动条件下,GCX的表达显着下降,并且与内皮或血管壁内的疾病样细胞和分子蓄积相吻合。GCX的治疗性修复消除了这种积累。结论再生降解的GCX可逆转EC屏障功能障碍,并可能减缓血管疾病的进展。
更新日期:2019-11-01
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