Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, South Africa.
Microsc Res Tech. 2013 Mar;76(3):268-71. doi: 10.1002/jemt.22163. Epub 2012 Dec 28.
Fibrinogen is key to the maintenance of hemostasis and is an acute phase protein that is part of the coagulation cascade of proteins. It plays a fundamental role in inflammation, particularly as indicator for a proinflammatory state and is a prominent marker for developing vascular inflammatory diseases. The ultrastructure of fibrin nets can be studied using scanning electron microscopy (SEM) with the addition of thrombin to plasma. In inflammatory conditions such as thromboembolic ischemic stroke and diabetes, the fibrin networks are changed to from dense matted fibrin deposits (DMDs) instead of typical netlike appearance. Similar DMDs can also be induced with the addition of FeCl(2) and FeCl(3). Importantly, the iron-induced DMDs look similar to those from patients with prothrombotic conditions. Excessive or misplaced tissue iron now is recognized to pose a substantial health risk. The current research therefore investigates the establishment of a laboratory fibrinogen model to study that might mimic fibrin fiber generation that is achieved using plasma from healthy and diseased individuals. Furthermore, to determine whether the addition of iron to purified fibrinogen will show DMDs and whether hydrophilic agents can prevent them. We conclude that SEM is a very effective tool for the visualization of circulatory consequences of the interaction of iron-induced hydroxyl radicals with human fibrinogen. Furthermore, this novel fibrinogen model provides a convenient method to study the interactions of the intramolecular and intermolecular hydrophobic forces responsible for the maintenance of the tertiary structure of native fibrin(ogen) and the prevention of iron-induced DMDs formation by hydrophilic agents.
纤维蛋白原是维持止血的关键，是一种急性期蛋白，也是蛋白质凝血级联反应的一部分。它在炎症中起着基本作用，特别是作为促炎状态的指标，也是发展血管炎症性疾病的重要标志物。纤维蛋白网络的超微结构可以使用扫描电子显微镜（SEM）研究，在向血浆中添加凝血酶后进行。在血栓栓塞性缺血性中风和糖尿病等炎症情况下，纤维蛋白网络会从典型的网状外观转变为密集的纤维状纤维沉积物（DMD）。类似的 DMD 也可以通过添加 FeCl(2)和 FeCl(3)来诱导。重要的是，铁诱导的 DMD 看起来与具有促血栓形成条件的患者的 DMD 相似。现在，过多或错位的组织铁被认为会带来重大的健康风险。因此，目前的研究旨在建立一种实验室纤维蛋白原模型，以研究可能模拟使用健康和患病个体的血浆实现的纤维蛋白纤维生成的模型。此外，为了确定向纯化纤维蛋白原中添加铁是否会显示 DMD，以及亲水剂是否可以预防它们。我们得出结论，SEM 是可视化铁诱导的羟基自由基与人类纤维蛋白原相互作用对循环系统影响的非常有效的工具。此外，这种新型纤维蛋白原模型提供了一种方便的方法来研究负责维持天然纤维蛋白原（原纤维蛋白）的三级结构和通过亲水剂防止铁诱导的 DMD 形成的分子内和分子间疏水力相互作用。
