Kovalenko Tatiana A, Giraud Marie-Noelle, Eckly Anita, Ribba Anne-Sophie, Proamer Fabienne, Fraboulet Sandrine, Podoplelova Nadezhda A, Valentin Jeremy, Panteleev Mikhail A, Gonelle-Gispert Carmen, Cook Stéphane, Lafanechère Laurence, Sveshnikova Anastasia N, Sadoul Karin
Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya str., 109029 Moscow, Russia.
Cardiology, Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland.
Cells. 2021 Mar 6;10(3):584. doi: 10.3390/cells10030584.
Primary hemostasis consists in the activation of platelets, which spread on the exposed extracellular matrix at the injured vessel surface. Secondary hemostasis, the coagulation cascade, generates a fibrin clot in which activated platelets and other blood cells get trapped. Active platelet-dependent clot retraction reduces the clot volume by extruding the serum. Thus, the clot architecture changes with time of contraction, which may have an important impact on the healing process and the dissolution of the clot, but the precise physiological role of clot retraction is still not completely understood. Since platelets are the only actors to develop force for the retraction of the clot, their distribution within the clot should influence the final clot architecture. We analyzed platelet distributions in intracoronary thrombi and observed that platelets and fibrin co-accumulate in the periphery of retracting clots in vivo. A computational mechanical model suggests that asymmetric forces are responsible for a different contractile behavior of platelets in the periphery versus the clot center, which in turn leads to an uneven distribution of platelets and fibrin fibers within the clot. We developed an in vitro clot retraction assay that reproduces the in vivo observations and follows the prediction of the computational model. Our findings suggest a new active role of platelet contraction in forming a tight fibrin- and platelet-rich boundary layer on the free surface of fibrin clots.
初级止血在于血小板的激活，血小板在受损血管表面暴露的细胞外基质上扩散。次级止血即凝血级联反应，会产生一个纤维蛋白凝块，激活的血小板和其他血细胞被困在其中。活跃的血小板依赖性凝块回缩通过挤出血清来减小凝块体积。因此，凝块结构会随着收缩时间而变化，这可能对愈合过程和凝块溶解产生重要影响，但凝块回缩的确切生理作用仍未完全了解。由于血小板是凝块回缩产生力量的唯一因素，它们在凝块中的分布应该会影响最终的凝块结构。我们分析了冠状动脉内血栓中的血小板分布，观察到在体内回缩凝块的周边血小板和纤维蛋白共同积聚。一个计算力学模型表明，不对称力导致凝块周边与凝块中心的血小板收缩行为不同，进而导致凝块内血小板和纤维蛋白纤维分布不均。我们开发了一种体外凝块回缩试验，该试验重现了体内观察结果并符合计算模型的预测。我们的研究结果表明，血小板收缩在纤维蛋白凝块自由表面形成紧密的富含纤维蛋白和血小板的边界层方面具有新的积极作用。
