Butschkau Antje, Wagner Nana-Maria, Bierhansl Laura, Genz Berit, Vollmar Brigitte
Institute for Experimental Surgery, Rostock University Medical Center Rostock, Germany.
Clinic for Anesthesiology and Critical Care Medicine, Rostock University Medical Center Rostock, Germany.
Int J Clin Exp Pathol. 2014 Aug 15;7(9):6064-71. eCollection 2014.
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.
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.
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.
蛋白Z（PZ）是一种无催化活性的维生素K依赖性凝血因子。有证据表明PZ是人类动脉粥样硬化性血管疾病发生的独立危险因素。本研究的目的是探讨PZ在血管动脉疾病中的作用。
利用氯化铁对PZ缺陷型（PZ(-/-)）小鼠及其野生型同窝小鼠（PZ(+/+)）进行单侧颈动脉损伤，21天后解剖进行组织学分析。用人主动脉平滑肌细胞（SMC）进行体外伤口愈合试验，以评估PZ对SMC迁移的影响，并进行细胞增殖研究。
新生内膜形成的形态计量学分析显示，与PZ(+/+)小鼠相比，PZ(-/-)小鼠颈动脉新生内膜的面积和厚度显著增加，随后管腔狭窄增加（p < 0.05，n = 9）。新生内膜病变组成的免疫组织化学分析显示，PZ(-/-)小鼠新生内膜中PCNA阳性和α-SMA阳性细胞的数量显著增加。此外，PZ在SMC的体外伤口愈合试验中显示出抗迁移能力，而未检测到PZ对SMC增殖有影响。结论：PZ有助于减少血管损伤后的新生内膜形成，强调了凝血级联在血管稳态中的调节作用。
