Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal; Thrombosis and Tissue Repair Group, Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine and Multidisciplinary Cardiovascular Centre, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Nanomedicine. 2018 Apr;14(3):909-918. doi: 10.1016/j.nano.2018.01.006. Epub 2018 Feb 2.
Plasma fibrinogen includes an alternatively spliced γ-chain variant (γ'), which mainly exists as a heterodimer (γAγ') and has been associated with thrombosis. We tested γAγ' fibrinogen-red blood cells (RBCs) interaction using atomic force microscopy-based force spectroscopy, magnetic tweezers, fibrin clot permeability, scanning electron microscopy and laser scanning confocal microscopy. Data reveal higher work necessary for RBC-RBC detachment in the presence of γAγ' rather than γAγA fibrinogen. γAγ' fibrinogen-RBCs interaction is followed by changes in fibrin network structure, which forms an heterogeneous clot structure with areas of denser and highly branched fibrin fibers. The presence of RBCs also increased the stiffness of γAγ' fibrin clots, which are less permeable and more resistant to lysis than γAγA clots. The modifications on clots promoted by RBCs-γAγ' fibrinogen interaction could alter the risk of thrombotic disorders.
血浆纤维蛋白原包括一个可变剪接的 γ 链变体 (γ')，主要以异二聚体 (γAγ')的形式存在，并与血栓形成有关。我们使用原子力显微镜基于力谱学、磁镊、纤维蛋白凝块渗透性、扫描电子显微镜和激光扫描共聚焦显微镜来测试 γAγ'纤维蛋白原-红细胞 (RBC) 的相互作用。数据显示，在存在 γAγ'而非 γAγA 纤维蛋白原的情况下，RBC-RBC 分离所需的功更高。γAγ'纤维蛋白原-RBC 相互作用后，纤维蛋白网络结构发生变化，形成具有更密集和高度分支纤维蛋白纤维区域的异质凝块结构。红细胞的存在也增加了 γAγ'纤维蛋白凝块的刚性，与 γAγA 凝块相比，γAγ'纤维蛋白凝块的渗透性降低，对溶解的抵抗力增强。红细胞-γAγ'纤维蛋白原相互作用对凝块的修饰可能会改变血栓形成紊乱的风险。
