Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed - Dynamic and structural approaches by confocal microscopy
Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed - Dynamic and structural approaches by confocal microscopy
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DOI：
10.1161/01.atv.20.5.1354
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发表时间：
2000-05-01
影响因子：
8.7
通讯作者：
Weisel, JW
中科院分区：
文献类型：
--
作者：
Collet, JP;Park, D;Weisel, JW
异常纤维蛋白结构被认为是低纤溶的决定因素。然而，由于缺乏纤维蛋白消化过程的结构知识，纤维蛋白结构与低纤溶之间的关系仍然存在争议。为了进一步阐明纤维蛋白溶解过程中发生的结构和动态变化，用胶体金颗粒标记交联血浆纤维蛋白，并用共聚焦显微镜观察纤维蛋白溶解过程。纤维蛋白网络和纤维水平的形态学改变。对纤维蛋白纤维渐进分解的观察强调，纤维蛋白溶解是通过横向切割进行的，而不是通过纤维周围均匀的渐进切割进行的。由细纤维构成的紧密纤维蛋白构象的血浆纤维蛋白凝块比由粗纤维构成的松散纤维蛋白凝块溶解的速度要慢，尽管总体纤维蛋白含量保持不变。出乎意料的是，细纤维比粗纤维劈裂得更快。对纤溶过程中fitc重组组织纤溶酶原激活物在纤维蛋白基质内分布的动态研究表明，粗纤维蛋白凝块的结合面比细血浆纤维蛋白凝块更宽，移动速度更快。这些动态和结构的方法纤维蛋白消化在网络和纤维水平揭示了凝块溶解的物理过程的各个方面。此外，这些结果为静脉血栓栓塞和过早冠状动脉疾病中与纤维蛋白结构缺陷相关的低纤溶提供了明确的解释。
Abnormal fibrin architecture is thought to be a determinant factor of hypofibrinolysis. However, because of the lack of structural knowledge of the process of fibrin digestion, relationships between fibrin architecture and hypofibrinolysis remain controversial. To elucidate further structural and dynamic changes occurring during fibrinolysis, cross-linked plasma fibrin was labeled with colloidal gold particles, and fibrinolysis was followed by confocal microscopy. Morphological changes were characterized at fibrin network and fiber levels. The observation of a progressive disaggregation of the fibrin fibers emphasizes that fibrinolysis proceeds by transverse cutting rather than by progressive cleavage uniformly around the fiber, Plasma fibrin clots with a tight fibrin conformation made of thin fibers were dissolved at a slower rate than those with a loose fibrin conformation made of thicker (coarse) fibers, although the overall fibrin content remained constant. Unexpectedly, thin fibers were cleaved at a faster late than thick ones. A dynamic study of FITC-recombinant tissue plasminogen activator distribution within the fibrin matrix during the course of fibrinolysis showed that the binding front was broader in coarse fibrin clots and moved more rapidly than that of fine plasma fibrin clots. These dynamic and structural approaches to fibrin digestion at the network and the fiber levels reveal aspects of the physical process of clot lysis. Furthermore, these results provide a clear explanation for the hypofibrinolysis related to a defective fibrin architecture as described in venous thromboembolism and in premature coronary artery disease.