Lipinski Boguslaw, Pretorius Etheresia
Joslin Diabetes Center, Harvard Medical School, Boston 02215, USA.
Pol Arch Med Wewn. 2012;122(3):115-22.
Fibrinogen (FBG) is a high-molecular-weight protein and precursor to the enzymatically formed fibrin. It has been recently discovered that FBG can be converted into an insoluble, fibrin-like polymer by a nonenzymatic action of hydroxyl radicals (HRs). These free radicals are generated due to the reaction between hydroxyl groups of water and trivalent ferric ions without the participation of any redox agent. The interaction between HRs and FBG occurs in a purified system, as well as in human plasma and in whole blood. Scanning electron microscopy (SEM) of thrombin-induced fibers and those generated with ferric chloride has shown substantial differences in their morphology and susceptibility to enzymatic degradation. Fibrin strands caused by thrombin are thick and easily digested with chymotrypsin. By contrast, the dense matted deposits formed from FBG in the presence of ferric ions are remarkably resistant to proteolytic and chemical degradations due to the presence of intermolecular hydrophobic bonds. Thus, we postulate that this iron-catalyzed reaction represents a novel blood coagulation pathway operating in degenerative diseases. By means of SEM, we showed the presence of dense fibrin-like deposits in the blood of diabetic patients. Therefore, the prothrombotic state and cardiovascular complications observed in diabetes can be explained in terms of the persistent in vivo action of free iron. This phenomenon may explain hemorheologic disturbances in patients with metabolic syndrome and other diseases caused by iron overload. Of note, HRs can be effectively scavenged by phenolic substances; therefore, certain natural polyphenolic substances, which also scavenge HRs, may be considered to have a potential antidiabetic effect. Moreover, natural or synthetic iron-binding substances may also be considered as a new class of antidiabetic drugs.
纤维蛋白原（FBG）是一种高分子量蛋白质，是酶促形成纤维蛋白的前体。最近发现，FBG可通过羟基自由基（HRs）的非酶促作用转化为不溶性的纤维蛋白样聚合物。这些自由基是由于水的羟基与三价铁离子之间的反应产生的，无需任何氧化还原剂的参与。HRs与FBG之间的相互作用发生在纯化系统、人体血浆和全血中。凝血酶诱导纤维以及用氯化铁生成的纤维的扫描电子显微镜（SEM）显示，它们在形态和对酶降解的敏感性方面存在显著差异。凝血酶引起的纤维蛋白链较粗，易被胰凝乳蛋白酶消化。相比之下，在铁离子存在下由FBG形成的致密缠结沉积物由于存在分子间疏水键，对蛋白水解和化学降解具有显著抗性。因此，我们推测这种铁催化反应代表了一种在退行性疾病中起作用的新型凝血途径。通过SEM，我们在糖尿病患者的血液中发现了致密的纤维蛋白样沉积物。因此，糖尿病中观察到的血栓前状态和心血管并发症可以用游离铁在体内的持续作用来解释。这种现象可能解释了代谢综合征患者和其他由铁过载引起的疾病中的血液流变学紊乱。值得注意的是，酚类物质可以有效清除HRs；因此，某些也能清除HRs的天然多酚类物质可能被认为具有潜在的抗糖尿病作用。此外，天然或合成的铁结合物质也可被视为一类新型抗糖尿病药物。
