1. Protein Z-deficiency is associated with enhanced neointima formation and inflammatory response after vascular injury in mice.
- Author
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Butschkau A, Wagner NM, Bierhansl L, Genz B, and Vollmar B
- Subjects
- Actins metabolism, Animals, Blood Proteins genetics, Carotid Arteries metabolism, Carotid Arteries pathology, Carotid Artery Injuries chemically induced, Carotid Artery Injuries genetics, Carotid Artery Injuries pathology, Cell Movement, Cell Proliferation, Cells, Cultured, Chlorides, Disease Models, Animal, Ferric Compounds, Humans, Inflammation chemically induced, Inflammation genetics, Inflammation pathology, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular injuries, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle pathology, Proliferating Cell Nuclear Antigen metabolism, Time Factors, Vascular System Injuries chemically induced, Vascular System Injuries genetics, Vascular System Injuries pathology, Blood Proteins deficiency, Carotid Artery Injuries metabolism, Inflammation metabolism, Muscle, Smooth, Vascular metabolism, Myocytes, Smooth Muscle metabolism, Neointima, Vascular System Injuries metabolism
- Abstract
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 aim of this study was to investigate the role of PZ in vascular arterial disease., 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., 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. Conclusion: PZ contributes to a reduced neointima formation after vascular injury, underlining the modulatory role of the coagulation cascade in vascular homeostasis.
- Published
- 2014