Background
Protein Z (PZ) is a vitamin K-dependent coagulation factor without catalytic activity. Evidence points towards PZ as an independent risk factor for the occurrence of human atherosclerotic vascular diseases. The
Conclusion
PZ contributes to a reduced neointima formation after vascular injury, underlining the modulatory role of the coagulation cascade in vascular homeostasis.
Material and methods
PZ-deficient (PZ(-/-)) mice and their wild-type littermates (PZ(+/+)) were subjected to unilateral carotid artery injury by using ferric chloride and dissected 21 days thereafter for histological analysis. Human aortic smooth muscle cells (SMC) were used for in vitro wound healing assay to assess the influence of PZ on SMC migration and for cell proliferation studies.
Methods
PZ-deficient (PZ(-/-)) mice and their wild-type littermates (PZ(+/+)) were subjected to unilateral carotid artery injury by using ferric chloride and dissected 21 days thereafter for histological analysis. Human aortic smooth muscle cells (SMC) were used for in vitro wound healing assay to assess the influence of PZ on SMC migration and for cell proliferation studies.
Results
Morphometric analysis of neointima formation revealed a significantly increased area and thickness of the neointima and subsequently increased luminal stenosis in carotid arteries of PZ(-/-) mice compared to PZ(+/+) mice (p < 0.05, n = 9). Immunohistochemical analysis of neointima lesion composition revealed significantly higher numbers of PCNA-positive and α-SMA-positive cells in the neointima of PZ(-/-) mice. Furthermore, PZ showed an anti-migratory potency in in vitro wound healing assay with SMCs, while no effect of PZ on SMC proliferation was detectable.