Deep Vein Thrombus Resolution In Gcsf Knockout Mice
Rick Mathews, BE, Anh Le-Cook, Gabriel Nager, Naly Setthavongsack, Randy Woltjer, MD, Monica Hinds, PhD, Khanh P. Nguyen, MD, MCR.
OHSU, Portland, OR, USA.
Objective: Previous studies have linked deep vein thrombus (DVT) resolution to the innate immune system and inflammation with T cell- directed monocyte recruitment, thrombus neovascularization and resolution. Impaired DVT resolution has been reported in mice deficient in neutrophils, monocytes, CXCR2 (neutrophil chemotactic factor) and toll like receptor 9. Granulocyte colony stimulating factor (GCSF) regulates proliferation and maturation of neutrophils from myeloid progenitors and promotes neutrophil mobilization from the bone marrow. GCSF deficient mice, humans, and zebrafish embryos exhibit neutropenia with mature granulocytes indicating GCSF dependent and independent signaling. We hypothesize that GCSF regulates venous thrombus resolution in a mouse model of occlusive DVT via a caval ligation mediated stasis model.
Methods: Male and female GCSF KO C57/BL6 and wild-type CD1 mice underwent surgical creation of a DVT via inferior vena cava (IVC) ligation. Mice were euthanized on postoperative days (POD) 3 and 7 to measure the relative resolution of thrombus by comparing measured thrombus weights normalized to thrombus length and body weight. Groups were tested for normality using a Shapiro-Wilk test and data visualization. Appropriate parametric or non-parametric tests were used to detect significant differences. All analysis was conducted in R and Python.
Results: On day 3 after IVC ligation mice, thrombus weight did not differ significantly between the control and knockout mice. By day 7, thrombus weight was significantly lower in the knockout group as compared to wildtype (P=.006, 2-sided t-test). This indicates that GCSF deficiency may facilitate thrombus resolution.
Conclusion: GCSF KO mice exhibited accelerated venous thrombus resolution in a stasis, model of DVT resolution as measured by thrombus weight normalized to thrombus length as compared to wildtype mice. These data suggest GCSF may regulate systemic neutrophil levels during venous DVT resolution.
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