Aging is associated with impaired thrombus resolution in a mouse model of stasis induced thrombosis

作者：McDonald April P; Meier Thomas R; Hawley Angela E; Thibert Jacklyn N; Farris Diana M; Wrobleski Shirley K; Henke Peter K; Wakefield Thomas W; Myers Daniel D Jr^*

来源：Thrombosis Research, 2010, 125(1): 72-78.

DOI：10.1016/j.thromres.2009.06.005

• Thrombus resolution
• Venous thrombosis
• Aging
• P-selectin
• PAI-1
• Microparticles
• Tissue factor activity
• Animal models

Introduction: To evaluate the effects of aging on venous thrombosis.
Material and Methods: Anesthetized male mice (C57BL/6, n = 125) underwent complete inferior vena cava occlusion to produce venous thrombosis. Experimental groups included 11-month-old mice (OLD), 2-month-old mice (YOUNG), and age-matched non-thrombosed controls. Mice were euthanized and the following parameters were evaluated two days post-thrombosis: thrombus mass (grams/cm), vein wall inflammatory cells (cells per 5 high powered fields), active plasma plasminogen activator inhibitor-1 (PAI-1, ng/mL), vein wall P-selectin protein determination by ELISA (pg/mL), circulating plasma microparticles (MPs, MPs/200 mu L), MP tissue factor (TF) activity (pM), and in vivo MP re-injection experiments.
Results: Thrombosed OLD mice had greater thrombus mass than YOUNG mice (389 +/- 18 vs. 336 +/- 14 g x 10(-4)/cm, P < .05). OLD mice had decreased vein wall monocyte, lymphocyte, and total inflammatory cell populations versus YOUNG mice (P < .05). Vein wall P-selectin levels were greater in OLD thrombosed mice versus YOUNG(7306 +/- 938 vs. 3805 +/- 745 pg/mL, P < .05). Active plasma PAI-1 concentrations were increased in OLD mice versus YOUNG thrombosed animals (20 +/- 4 vs. 8 +/- 2 ng/mL, P < .05). OLD mice had significantly higher circulating leukocyte-derived MPs versus YOUNG mice (5817 +/- 850 vs. 2563 +/- 283 MPs/200 mu L PPP, P < .01). OLD mice had plasma MPs with increased TF activity versus YOUNG animals post-thrombosis (34 +/- 4 vs. 24 +/- 2 pM, P < .05). Finally, YOUNG recipient animals, whether re-injected with OLD or YOUNG donor MPs, had a significant increase in thrombus mass versus OLD recipient animals (P < .01).
Conclusion: Aging influenced several circulating and vein wall factors that decreased thrombus resolution in older animals compared to younger ones in our mouse thrombosis model.

• 出版日期2010-1