Endothelial cell adhesion to the fibronectin CS5 domain in artificial extracellular matrix proteins
Endothelial cell adhesion to the fibronectin CS5 domain in artificial extracellular matrix proteins
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DOI：
10.1016/s0142-9612(03)00294-1
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发表时间：
2003-10-01
期刊：
影响因子：
14
通讯作者：
Tirrell, DA
中科院分区：
文献类型：
--
作者：
Heilshorn, SC;DiZio, KA;Tirrell, DA
本研究检测了人脐静脉内皮细胞(HUVEC)在含有弹性蛋白和纤维连接蛋白序列的人工细胞外基质(AECM)蛋白上的扩散和黏附。研究了AECM的三个变异体：AECM 1含有蛋白序列中周期性间隔的赖氨酸残基和纤维连接蛋白CS5结构域的3个重复，AECM 2包含周期性间隔的赖氨酸和3个加扰的CS5序列重复，AECM 3包含蛋白质末端的赖氨酸和5个CS5重复。比较细胞结合和肽抑制分析证实，四肽序列REDV负责HUVEC与含有CS5结构域的AECM蛋白的黏附。此外，在生理剪应力(小于或等于100dynes/cm(2))下，60%以上的贴壁HUVEC被保留在AECM 1上。AECM-1上HUVEC单层分泌的血栓标志物(组织型纤溶酶原激活物和纤溶酶原激活物抑制物1)水平与纤维连接蛋白培养的HUVEC单层相似。这些特性，以及由这些材料制备的交联膜的物理强度和弹性，使AECM蛋白有望应用于小直径血管移植物。(C)2003爱思唯尔有限公司。保留所有权利。
This study examines the spreading and adhesion of human umbilical vein endothelial cells (HUVEC) on artificial extracellular matrix (aECM) proteins containing sequences derived from elastin and fibronectin. Three aECM variants were studied: aECM 1 contains lysine residues periodically spaced within the protein sequence and three repeats of the CS5 domain of fibronectin, aECM 2 contains periodically spaced lysines and three repeats of a scrambled CS5 sequence, and aECM 3 contains lysines at the protein termini and five CS5 repeats. Comparative cell binding and peptide inhibition assays confirm that the tetrapeptide sequence REDV is responsible for HUVEC adhesion to aECM proteins that contain the CS5 domain. Furthermore, more than 60% of adherent HUVEC were retained on aECM 1 after exposure to physiologically relevant shear stresses (less than or equal to 100 dynes/cm(2)). Finally, the levels of thrombogenic markers (tissue plasminogen activator and plasminogen activator inhibitor 1) secreted by HUVEC monolayers on aECM 1 were found to be similar to those secreted by HUVEC monolayers cultured on fibronectin. These characteristics, along with the physical strength and elasticity of crosslinked films prepared from these materials, make aECM proteins promising candidates for application in small-diameter vascular grafts. (C) 2003 Elsevier Ltd. All rights reserved.