Shear stimulated red blood cell microparticles: Effect on clot structure, flow and fibrinolysis.

IF 1 4区医学 Q4 BIOPHYSICS Biorheology Pub Date : 2023-01-01 DOI:10.3233/BIR-220012

James P Buerck, Kylie M Foster, Preston R Larson, Edgar A O'Rear

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Abstract

Background: Microparticles (MPs) have activity in thrombus promotion and generation. Erythrocyte microparticles (ErMPs) have been reported to accelerate fibrinolysis in the absence of permeation. We hypothesized that shear induced ErMPs would affect fibrin structure of clots and change flow with implications for fibrinolysis.

Objective: To determine the effect of ErMPs on clot structure and fibrinolysis.

Methods: Plasma with elevated ErMPs was isolated from whole blood or from washed red blood cells (RBCs) resuspended in platelet free plasma (PFP) after high shear. Dynamic light scattering (DLS) provided size distribution of ErMPs from sheared samples and unsheared PFP controls. Clots were formed by recalcification for flow/lysis experiments and examined by confocal microscopy and SEM. Flow rates through clots and time-to-lysis were recorded. A cellular automata model showed the effect of ErMPs on fibrin polymerization and clot structure.

Results: Coverage of fibrin increased by 41% in clots formed from plasma of sheared RBCs in PFP over controls. Flow rate decreased by 46.7% under a pressure gradient of 10 mmHg/cm with reduction in time to lysis from 5.7 ± 0.7 min to 12.2 ± 1.1 min (p < 0.01). Particle size of ErMPs from sheared samples (200 nm) was comparable to endogenous microparticles.

Conclusions: ErMPs alter the fibrin network in a thrombus and affect hydraulic permeability resulting in decelerated delivery of fibrinolytic drugs.

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剪切刺激红细胞微粒：对血凝块结构、流动和纤维蛋白溶解的影响

背景：微颗粒（MPs）具有促进和生成血栓的活性。据报道，红细胞微颗粒（ErMPs）可在无渗透的情况下加速纤维蛋白溶解。我们假设剪切力诱导的 ErMPs 会影响血块的纤维蛋白结构并改变血流，从而对纤维蛋白溶解产生影响：确定 ErMPs 对血凝块结构和纤维蛋白溶解的影响：方法：从全血或高剪切力后重新悬浮在无血小板血浆（PFP）中的洗红细胞（RBC）中分离出 ErMPs 升高的血浆。动态光散射（DLS）提供了剪切样品和未剪切无血小板血浆对照组中 ErMPs 的粒度分布。通过重新煅烧形成凝块，用于流动/溶解实验，并通过共聚焦显微镜和扫描电镜进行检测。记录了通过凝块的流速和溶解时间。细胞自动机模型显示了 ErMPs 对纤维蛋白聚合和凝块结构的影响：结果：与对照组相比，PFP 中剪切的 RBC 血浆形成的凝块的纤维蛋白覆盖率增加了 41%。在 10 mmHg/cm 的压力梯度下，流速降低了 46.7%，裂解时间从 5.7 ± 0.7 分钟缩短至 12.2 ± 1.1 分钟（p < 0.01）。剪切样品中的 ErMPs 颗粒大小（200 nm）与内源性微颗粒相当：结论：ErMPs改变了血栓中的纤维蛋白网络，影响了水力渗透性，导致纤溶药物的输送速度减慢。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biorheology 医学-工程：生物医学

CiteScore

2.00

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Biorheology is an international interdisciplinary journal that publishes research on the deformation and flow properties of biological systems or materials. It is the aim of the editors and publishers of Biorheology to bring together contributions from those working in various fields of biorheological research from all over the world. A diverse editorial board with broad international representation provides guidance and expertise in wide-ranging applications of rheological methods to biological systems and materials. The scope of papers solicited by Biorheology extends to systems at different levels of organization that have never been studied before, or, if studied previously, have either never been analyzed in terms of their rheological properties or have not been studied from the point of view of the rheological matching between their structural and functional properties. This biorheological approach applies in particular to molecular studies where changes of physical properties and conformation are investigated without reference to how the process actually takes place, how the forces generated are matched to the properties of the structures and environment concerned, proper time scales, or what structures or strength of structures are required.