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

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

doi:10.1016/j.thromres.2009.06.005

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

April P. McDonald, Thomas R. Meier, Angela E. Hawley, Jacklyn N. Thibert, Diana M. Farris, Shirley K. Wrobleski, Peter K. Henke, Thomas W. Wakefield, Daniel D. Myers

Comparative Medicine (Veterinary Medicine)

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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 μL), 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 × 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 μL 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.

Original language	English (US)
Pages (from-to)	72-78
Number of pages	7
Journal	Thrombosis research
Volume	125
Issue number	1
DOIs	https://doi.org/10.1016/j.thromres.2009.06.005
State	Published - Jan 2010

Keywords

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

ASJC Scopus subject areas

Hematology

Access to Document

10.1016/j.thromres.2009.06.005

Cite this

@article{58909fc3919f47f7bad9ced010f00228,

title = "Aging is associated with impaired thrombus resolution in a mouse model of stasis induced thrombosis",

abstract = "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 μL), 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 × 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 μL 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.",

keywords = "Aging, Animal models, Microparticles, P-selectin, PAI-1, Thrombus resolution, Tissue factor activity, Venous thrombosis",

author = "McDonald, {April P.} and Meier, {Thomas R.} and Hawley, {Angela E.} and Thibert, {Jacklyn N.} and Farris, {Diana M.} and Wrobleski, {Shirley K.} and Henke, {Peter K.} and Wakefield, {Thomas W.} and Myers, {Daniel D.}",

note = "Funding Information: Financial support was obtained from the Diversity & Career Development Office (DCDO) [to DDM], Esperance Family Foundation (to APM), and Department of Surgery University of Michigan (to DDM). We thank Ms. Iris Richardson for her technical assistance.",

year = "2010",

month = jan,

doi = "10.1016/j.thromres.2009.06.005",

language = "English (US)",

volume = "125",

pages = "72--78",

journal = "Thrombosis research",

issn = "0049-3848",

publisher = "Elsevier Limited",

number = "1",

}

TY - JOUR

T1 - Aging is associated with impaired thrombus resolution in a mouse model of stasis induced thrombosis

AU - McDonald, April P.

AU - Meier, Thomas R.

AU - Hawley, Angela E.

AU - Thibert, Jacklyn N.

AU - Farris, Diana M.

AU - Wrobleski, Shirley K.

AU - Henke, Peter K.

AU - Wakefield, Thomas W.

AU - Myers, Daniel D.

N1 - Funding Information: Financial support was obtained from the Diversity & Career Development Office (DCDO) [to DDM], Esperance Family Foundation (to APM), and Department of Surgery University of Michigan (to DDM). We thank Ms. Iris Richardson for her technical assistance.

PY - 2010/1

Y1 - 2010/1

N2 - 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 μL), 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 × 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 μL 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.

AB - 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 μL), 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 × 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 μL 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.

KW - Aging

KW - Animal models

KW - Microparticles

KW - P-selectin

KW - PAI-1

KW - Thrombus resolution

KW - Tissue factor activity

KW - Venous thrombosis

UR - http://www.scopus.com/inward/record.url?scp=76449089247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76449089247&partnerID=8YFLogxK

U2 - 10.1016/j.thromres.2009.06.005

DO - 10.1016/j.thromres.2009.06.005

M3 - Article

C2 - 19616825

AN - SCOPUS:76449089247

SN - 0049-3848

VL - 125

SP - 72

EP - 78

JO - Thrombosis research

JF - Thrombosis research

IS - 1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this