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狒狒血管内皮细胞生长过程中动态剪应力对炎症和血栓形成途径的调节作用。

Dynamic shear stress regulation of inflammatory and thrombotic pathways in baboon endothelial outgrowth cells.

机构信息

Parker H. Petit Institute for Bioengineering and Bioscience and Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.

出版信息

Tissue Eng Part A. 2013 Jul;19(13-14):1573-82. doi: 10.1089/ten.TEA.2012.0300. Epub 2013 Mar 19.

DOI:10.1089/ten.TEA.2012.0300
PMID:23406430
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3665318/
Abstract

Endothelial outgrowth cells (EOCs) have garnered much attention as a potential autologous endothelial source for vascular implants or in tissue engineering applications due to their ease of isolation and proliferative ability; however, how these cells respond to different hemodynamic cues is ill-defined. This study investigates the inflammatory and thrombotic response of baboon EOCs (BaEOCs) to four hemodynamic conditions using the cone and plate shear apparatus: steady, laminar shear stress (SS); pulsatile, nonreversing laminar shear stress (PS); oscillatory, laminar shear stress (OS); and net positive, pulsatile, reversing laminar shear stress (RS). In summary, endothelial nitric oxide synthase (eNOS) mRNA was significantly upregulated by SS compared to OS. No differences were found in the mRNA levels of the inflammatory markers intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) between the shear conditions; however, OS significantly increased the number of monocytes bound when compared to SS. Next, SS increased the anti-thrombogenic mRNA levels of CD39, thrombomodulin, and endothelial protein-C receptor (EPCR) compared to OS. SS also significantly increased CD39 and EPCR mRNA levels compared to RS. Finally, no significant differences were detected when comparing pro-thrombotic tissue factor mRNA or its activity levels. These results indicate that shear stress can have beneficial (SS) or adverse (OS, RS) effects on the inflammatory or thrombotic potential of EOCs. Further, these results suggest SS hemodynamic preconditioning may be optimal in increasing the efficacy of a vascular implant or in tissue-engineered applications that have incorporated EOCs.

摘要

内皮细胞外生(EOC)因其易于分离和增殖能力而备受关注,成为血管植入物或组织工程应用中的潜在自体内皮来源;然而,这些细胞对不同血流动力学线索的反应方式仍不清楚。本研究使用锥板剪切仪研究了狒狒 EOC(BaEOC)对四种血流动力学条件的炎症和血栓形成反应:稳态、层流剪切应力(SS);脉动、非反转层流剪切应力(PS);振荡、层流剪切应力(OS);以及净正、脉动、反转层流剪切应力(RS)。总之,与 OS 相比,SS 显著上调了内皮一氧化氮合酶(eNOS)mRNA。在剪切条件之间,炎症标志物细胞间黏附分子-1(ICAM-1)、E-选择素和血管细胞黏附分子-1(VCAM-1)的 mRNA 水平没有差异;然而,与 SS 相比,OS 显著增加了结合的单核细胞数量。接下来,与 OS 相比,SS 增加了抗血栓形成的 CD39、血栓调节蛋白和内皮蛋白 C 受体(EPCR)的 mRNA 水平。与 RS 相比,SS 还显著增加了 CD39 和 EPCR 的 mRNA 水平。最后,当比较促血栓形成组织因子 mRNA 或其活性水平时,没有检测到显著差异。这些结果表明,剪切应力对 EOC 的炎症或血栓形成潜力可能具有有益(SS)或不利(OS、RS)影响。此外,这些结果表明,SS 血流预处理可能是增加血管植入物或包含 EOC 的组织工程应用疗效的最佳选择。

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