Abstract
The effect of ageing on the morphology of veins, venous valves and arteries was investigated in male wild-type mice using an adapted procedure with injection of a silicone polymer Microfil® that preserves morphology of the vasculature. Throughout the hind limb the arterial, but not the venous, lumen area and wall thickness were significantly greater in 24-month as compared to 10-week-old C57BL/6 mice. Venous valves were most frequently located at the sapheno-femoral vein junction in the lower extremities, and appeared thicker at the base supported by structurally intact collagen fibers, and thinner towards the proximal end of the valve leaflet, with less organized collagen. Overall, valves were less supported by structurally intact collagen at 24 months as compared to 10 weeks. Endothelial expression of CD31, endothelial protein C receptor or von Willebrand factor (VWF) was not affected by age, while thrombomodulin expression was lower in aged versus young arteries. At both ages, expression of VWF was lower at venous valves versus veins. Evaluation of the blood coagulation profile revealed that aged mice had shortened prothrombin time, elevated plasma levels of factor (F)VII, FVIII and VWF and increased neutrophil and platelet counts. Thus, our data indicate that in mice with ageing, venous valves become more fragile, in association with a procoagulant and inflammatory blood phenotype. Taken together, we found that the procoagulant state in ageing, is accompanied by mild vascular changes.
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Acknowledgments
We acknowledge Annemie De Wolf, Christine Vranckx, and Soetkin Van Kerckhoven for excellent technical assistance. We are grateful to Prof. Eric Verbeken for use of his polarization microscope. We thank Prof. Dr. Chuck Esmon (Oklahoma Medical Research Foundation, OK, USA) for a kind gift of the TM and EPCR antibodies. The Center for Molecular and Vascular Biology is supported by the “Programmafinanciering Katholieke Universiteit Leuven” (PF/10/014). This study was supported by FWO project G.0678.10 and by LINAT (Leducq International Network against Thrombosis).
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Hemmeryckx, B., Emmerechts, J., Bovill, E.G. et al. Effect of ageing on the murine venous circulation. Histochem Cell Biol 137, 537–546 (2012). https://doi.org/10.1007/s00418-012-0913-8
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DOI: https://doi.org/10.1007/s00418-012-0913-8