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/200microL), 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 gx10(-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+/-745pg/mL, P<.05). Active plasma PAI-1 concentrations were increased in OLD mice versus YOUNG thrombosed animals (20+/-4 vs. 8+/-2ng/mL, P<.05). OLD mice had significantly higher circulating leukocyte-derived MPs versus YOUNG mice (5817+/-850 vs. 2563+/-283 MPs/200muL 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.