Histological and biomechanical changes in a mouse model of venous thrombus remodeling.
BACKGROUND
Deep vein thrombosis and the risk of pulmonary embolism are significant causes of morbidity and mortality. Much remains unclear, however, about the mechanisms by which a venous thrombus initiates, progresses, or resolves. In particular, there is a pressing need to characterize the evolving mechanical properties of a venous thrombus for its mechanical integrity is fundamental to many disease sequelae.


OBJECTIVE
The primary goal of the present study was to initiate a correlation between evolving histological changes and biomechanical properties of venous thrombus.


METHODS
We employed an inferior vena cava ligation model in mice to obtain cylindrical samples of thrombus that were well suited for mechanical testing and that could be explanted at multiple times following surgery. Using uniaxial micro-mechanical testing, we collected stress-stretch data that were then fit with a microstructurally-inspired material model before submitting the samples to immunohistological examination.


RESULTS
We found that venous thrombus underwent a radially inward directed replacement of fibrin with collagen between 2 weeks and 4 weeks of development, which was accompanied by the infiltration of inflammatory and mesenchymal cells. These histological changes correlated with a marked increase in material stiffness.


CONCLUSIONS
We demonstrated that 2 to 4 week old venous thrombus undergoes drastic remodeling from a fibrin-dominated mesh to a collagen-dominated microstructure and that these changes are accompanied by dramatic changes in biomechanical behavior.
['Lee|Y-U|YU|', 'Lee|A Y|AY|', 'Humphrey|J D|JD|', 'Rausch|M K|MK|']
D000818:Animals D001696:Biomechanical Phenomena D003094:Collagen D004195:Disease Models, Animal D005337:Fibrin D006801:Humans D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D066253:Vascular Remodeling D014682:Vena Cava, Inferior D020246:Venous Thrombosis
stiffness Venous ligation clot intraluminal thrombosis stress