Internal fibrinolysis of fibrin clots is driven by pore expansion.
Internal fibrinolysis of fibrin clots is driven by pore expansion.
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DOI：
10.1038/s41598-024-52844-4
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发表时间：
2024-02-01
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
血凝块由血细胞和稳定的纤维蛋白纤维网组成，在受伤后停止出血中至关重要。然而，它们的作用是短暂的，并且在执行其生理功能之后，它们必须通过称为纤维蛋白溶解的过程来解决。内部纤维蛋白溶解是通过血流中内源性或先天存在的溶解酶降解纤维蛋白;在健康条件下，该过程调节止血并防止出血或凝血。纤维蛋白结合的组织纤溶酶原激活物（tPA）将附近的纤溶酶原转化为活性纤溶酶，其结合到纤维蛋白网络，将其分解成纤维蛋白降解产物并释放截留的血细胞。目前尚不清楚纤维蛋白结构和溶解蛋白比例的变化如何影响内部纤维蛋白溶解的生化调节和行为。我们使用浊度动力学跟踪和显微镜与数学建模配对，研究纤维蛋白结构和溶解蛋白的比例，限制内部纤溶。模拟和实验的分析表明，纤维蛋白溶解是由纤维蛋白网络的孔扩张驱动的。我们发现，这种效果是强烈的纤维蛋白：tPA的比例相比，绝对tPA浓度的影响。因此，在实验和临床研究内部纤溶时，考虑相对蛋白浓度是必要的。对有效内溶解的更好理解可以帮助开发更好的治疗出血和血栓形成的疗法。
Blood clots, which are composed of blood cells and a stabilizing mesh of fibrin fibers, are critical in cessation of bleeding following injury. However, their action is transient and after performing their physiological function they must be resolved through a process known as fibrinolysis. Internal fibrinolysis is the degradation of fibrin by the endogenous or innate presence of lytic enzymes in the bloodstream; under healthy conditions, this process regulates hemostasis and prevents bleeding or clotting. Fibrin-bound tissue plasminogen activator (tPA) converts nearby plasminogen into active plasmin, which is bound to the fibrin network, breaking it down into fibrin degradation products and releasing the entrapped blood cells. It is poorly understood how changes in the fibrin structure and lytic protein ratios influence the biochemical regulation and behavior of internal fibrinolysis. We used turbidity kinetic tracking and microscopy paired with mathematical modeling to study fibrin structure and lytic protein ratios that restrict internal fibrinolysis. Analysis of simulations and experiments indicate that fibrinolysis is driven by pore expansion of the fibrin network. We show that this effect is strongly influenced by the ratio of fibrin:tPAwhen compared to absolute tPA concentration. Thus, it is essential to consider relative protein concentrations when studying internal fibrinolysis both experimentally and in the clinic. An improved understanding of effective internal lysis can aid in development of better therapeutics for the treatment of bleeding and thrombosis.
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影响因子：
3.4
作者：
Li W;Sigley J;Pieters M;Helms CC;Nagaswami C;Weisel JW;Guthold M
通讯作者：
Guthold M
DOI：
10.1161/01.atv.0000241589.52950.4c
发表时间：
2006-11-01
影响因子：
8.7
作者：
Collet, J. P.;Allali, Y.;Montalescot, G.
通讯作者：
Montalescot, G.
DOI：
10.1093/imammb/dqs029
发表时间：
2014-03-01
影响因子：
1.1
作者：
Bannish, Brittany E.;Keener, James P.;Fogelson, Aaron L.
通讯作者：
Fogelson, Aaron L.
影响因子：
7.3
作者：
Litvinov, Rustem;Nabiullina, Rosa M.;Weisel, John W.
通讯作者：
Weisel, John W.
DOI：
10.1161/atvbaha.117.308564
发表时间：
2017-03
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Kattula S;Byrnes JR;Wolberg AS
通讯作者：
Wolberg AS