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Male mice have increased thrombotic potential: Sex differences in a mouse model of venous thrombosis
被引:31
作者:
Alvarado, Christine M.
[1
,2
]
Diaz, Jose A.
[1
]
Hawley, Angela E.
[1
]
Wrobleski, Shirley K.
[1
]
Sigler, Robert E.
[3
]
Myers, Daniel D., Jr.
[1
,2
]
机构:
[1] Univ Michigan, Vasc Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Unit Lab Anim Med, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Res Essential Serv, LLC, Ann Arbor, MI 48109 USA
关键词:
Venous thrombosis;
Sex differences;
Animal model;
Inflammation;
Thrombogenesis;
Thrombus resolution;
NECROSIS-FACTOR-ALPHA;
DEEP-VEIN THROMBOSIS;
TISSUE FACTOR;
P-SELECTIN;
THROMBOEMBOLISM;
DIMORPHISM;
RESOLUTION;
CYTOKINES;
FIBRIN;
MEN;
D O I:
10.1016/j.thromres.2011.01.004
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Introduction: Our objectives were to characterize sex differences during venous thrombosis, using the electrolytic inferior vena cava model of the disease. Materials and methods: Male and female C57BL/6 mice (6-8 weeks) underwent inferior vena cava thrombosis. Time points included 6 hours, day 2, day 6, and day 14 post surgery, along with surgically nave true controls and surgical shams. Analyses included thrombus weight, vein wall morphometrics, vein wall protein and gene expression for P-selectin, interleukin-1 beta, and tumor necrosis factor-alpha; hematology, soluble P-selectin, and plasma microparticle tissue factor activity assays. Results: Male venous thrombi were significantly larger than females at days 2 (13.1+/-1.0 vs. 6.8+/-0.5x10(-3) grams, p<0.01), 6 (10.4+/-0.8 vs. 5.4+/-0.5x10(-3) grams, p<0.01) and 14 (6.3+/-0.5 vs. 4.1+/-0.3x10(-3) grams, p<0.01). Both male and female mice exhibited significantly increased vein wall P-selectin at 6 hours, vs. true controls (p<0.05). Males had increased vein wall interleukin-1 beta, versus females, at 6 hours (180.926+/-24.596 vs. 60.417+/-10.478 pg/mL, p<0.05) and day 6 (76.966+/-13.081 vs. 33.834+/-4.198 pg/mL, p<0.01). Males showed decreased tumor necrosis factor-a expression (-66%) at 6 hours. Females had increased tumor necrosis factor-a expression at 6 hours (+541%) and day 6 (+539%). Both sexes demonstrated decreased peripheral platelets at 6 hours (p<0.05), coinciding with thrombogenesis. Plasma P-selectin increased in both sexes, versus controls, through day 6 (p<0.05). Conclusions: Males had significantly larger venous thrombi than females. Sex differences in vascular anatomy and response to inflammation may influence thrombus formation in our mouse thrombosis model. (C) 2011 Elsevier Ltd. All rights reserved.
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页码:478 / 486
页数:9
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