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Thromb Haemost 2009; 101(04): 748-754
DOI: 10.1160/TH08-09-0620
Animal Models
Schattauer GmbH

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

Eduardo Ramacciotti
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Angela E. Hawley
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Diana M. Farris
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Nicole E. Ballard
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Shirley K. Wrobleski
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Daniel D. Myers Jr
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
2   Unit for Laboratory Animal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Peter K. Henke
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Thomas W. Wakefield
1   Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA
› Author AffiliationsFinancial support: This study was supported by NIH HL070766, NIH NCRR 5P41RR018627 and State of Michigan, MEDC GR239.
Further Information

Publication History

Received: 29 September 2008

Accepted after major revision: 25 January 2009

Publication Date:
23 November 2017 (online)

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Summary

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 (ΔCT). 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 ΔCT 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.

Keywords

Venous thrombosis - inflammation - microparticles - plasminogen - tissue factor - tissue factor activity - animal models
 

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