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

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. (C) 2009 Elsevier Ltd. All rights reserved.