Aging is associated with impaired thrombus resolution in a mouse model of stasis induced thrombosis.
BACKGROUND
To evaluate the effects of aging on venous thrombosis.


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).


CONCLUSIONS
Aging influenced several circulating and vein wall factors that decreased thrombus resolution in older animals compared to younger ones in our mouse thrombosis model.
McDonald
April P
AP
Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0654. USA.
Meier
Thomas R
TR
Hawley
Angela E
AE
Thibert
Jacklyn N
JN
Farris
Diana M
DM
Wrobleski
Shirley K
SK
Henke
Peter K
PK
Wakefield
Thomas W
TW
Myers
Daniel D
DD
D000375:Aging / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology*; D020246:Venous Thrombosis / Q000378:metabolism / Q000473:pathology*
D019007:P-Selectin; D017395:Plasminogen Activator Inhibitor 1; D013925:Thromboplastin