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在静脉血栓形成的实验小鼠模型中,白细胞和血小板衍生的微粒与血栓重量及组织因子活性相关。

Leukocyte- and platelet-derived microparticles correlate with thrombus weight and tissue factor activity in an experimental mouse model of venous thrombosis.

作者信息

Ramacciotti Eduardo, Hawley Angela E, Farris Diana M, Ballard Nicole E, Wrobleski Shirley K, Myers Daniel D, Henke Peter K, Wakefield Thomas W

机构信息

Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical School Center, Ann Arbor, MI, USA.

出版信息

Thromb Haemost. 2009 Apr;101(4):748-54.

Abstract

Microparticles (MP) are lipid vesicles from platelets, leukocytes and endothelial cells that are involved in early thrombogenesis. We evaluated a detailed time-course analysis of MPs on thrombogenesis and the associated tissue factor (TF) activity in wild-type, in gene-deleted for E- and P-selectins and with high levels of P-selectin expression after the initiation of venous thrombosis in mice. Inferior vena cava (IVC) ligation was performed on C57BL/6 mice (n = 191, 59 = wild-type [WT], 55 = gene-deleted for E- and P - selectins [knock-outs, EPKO] and 77 = elevated levels of soluble P-selectin, named Delta Cytoplasmic Tail (DeltaCT). Animals were euthanised at various time points to assess MP production, origin and thrombus weight. MPs were re-injected into separate mice at concentrations of 80,000 and 160,000 units, as well as from different ages. In addition, MPs from thrombosed animals were pooled and TF activity quantitated using a chromogenic assay. Thrombus weight correlated negatively with MPs derived from leukocytes, and positively with MPs derived from platelets for WT animals (p < 0.05), while MPs from platelets presented a positive correlation to thrombus weight in the WT and EPKO groups (p < 0.01). Total MPs correlated negatively with thrombus weight in the DeltaCT group (p < 0.05). MP re-injections led to greater thrombus weight, while older MP reinjections tended to form larger thrombus than younger. Finally, TF bearing MPs showed a significant correlation to MP concentrations (R = 0.99). In conclusion, MPs appear to be an important element in venous thrombogenesis.

摘要

微粒(MP)是来自血小板、白细胞和内皮细胞的脂质囊泡,参与早期血栓形成。我们评估了在野生型小鼠、E-选择素和P-选择素基因缺失小鼠以及静脉血栓形成起始后P-选择素表达水平高的小鼠中,微粒对血栓形成及相关组织因子(TF)活性的详细时间进程分析。对C57BL/6小鼠(n = 191,59只 = 野生型[WT],55只 = E-选择素和P-选择素基因缺失[基因敲除,EPKO],77只 = 可溶性P-选择素水平升高,称为Delta细胞质尾[DeltaCT])进行下腔静脉(IVC)结扎。在不同时间点对动物实施安乐死,以评估微粒的产生、来源和血栓重量。将微粒以80,000和160,000单位的浓度以及不同年龄重新注射到单独的小鼠体内。此外,将来自形成血栓动物的微粒汇集起来,使用显色测定法定量TF活性。对于野生型动物,血栓重量与源自白细胞的微粒呈负相关,与源自血小板的微粒呈正相关(p < 0.05),而在野生型和EPKO组中,源自血小板的微粒与血栓重量呈正相关(p < 0.01)。在DeltaCT组中,总微粒与血栓重量呈负相关(p < 0.05)。重新注射微粒导致血栓重量增加,而注射较老的微粒往往比注射较年轻的微粒形成更大的血栓。最后,携带TF的微粒与微粒浓度呈显著相关性(R = 0.99)。总之,微粒似乎是静脉血栓形成中的一个重要因素。

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