In this study, we investigated how carbonylation of fibrinogen by acrolein modified its indispensable function to enhance fibrinolysis after being converted to fibrin and contributed to generating a fibrinolysis-resistant fibrin clot. Acrolein-treated fibrinogen was subjected to tissue plasminogen activator-induced fibrinolysis assay and the effect of lysine residue carbonylation in fibrinogen on fibrinolysis was analyzed. The acrolein-treated fibrinogen-derived fibrin clot appeared more resistant to fibrinolysis and the N-acetyl 3-formyl-3,4-dehydropiperidino (FDP)-Lysine levels in the lysed solution were positively correlated with the duration of clot lysis. The lysine analog 6-amino hexanoic acid (6AHA), which mimics the C-terminal lysine of fibrin, was carbonylated and its enhancing effect on Glu₁-plasminogen activation was evaluated. After incubation with acrolein, 6AHA was converted to N-acetyl FDP-6AHA, losing its ability to enhance Glu₁-plasminogen activation. These results suggest that fibrinogen carbonylation by acrolein to generate N-acetyl FDP-Lysine resulted in the generation of fibrinolysis-resistant fibrin by attenuating the C-terminal lysine-dependent activation of the Glu₁-plasminogen. In abdominal aortic aneurysms, fibrin(ogen) containing the acrolein adduct N-acetyl FDP-Lysine was detected in the vascular wall-attached thrombi. These results suggest that this mechanism is likely involved in the modification of fibrinolysis-resistant thrombi and to their persistence for a long period.

在这项研究中，我们研究了丙烯醛对血纤蛋白原的羰基化作用如何在转化为血纤蛋白后修饰其必不可少的功能，以增强血纤蛋白溶解并有助于产生抗血纤蛋白的血纤蛋白凝块。对经丙烯醛处理的纤维蛋白原进行组织纤维蛋白溶酶原激活剂诱导的纤维蛋白溶解测定，并分析了纤维蛋白原中赖氨酸残基羰基化对纤维蛋白溶解的影响。经丙烯醛处理的纤维蛋白原来源的纤维蛋白凝块似乎对纤维蛋白溶解更有抵抗力，并且溶解溶液中的N-乙酰基3-甲酰基-3,4-脱氢哌啶子酮（FDP）-赖氨酸水平与凝块溶解时间呈正相关。模拟血纤蛋白C端赖氨酸的赖氨酸类似物6-氨基己酸（6AHA）被羰基化并增强了对Glu _1的作用评估了纤溶酶原的活化。与丙烯醛温育后，6AHA转化为N-乙酰基FDP-6AHA，失去了增强Glu _1-纤溶酶原激活的能力。这些结果表明，丙烯醛将纤维蛋白原羰基化以产生N-乙酰基FDP-赖氨酸，通过减弱Glu _1-纤溶酶原的C-端赖氨酸依赖性活化而产生抗纤维蛋白溶解的纤维蛋白。在腹主动脉瘤中，在附有血管壁的血栓中检测到含有丙烯醛加合物N-乙酰基FDP-赖氨酸的纤维蛋白（原）。这些结果表明，该机制可能参与了抗纤溶性血栓的修饰及其长期持续性。