Danziger John
Renal Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Clin J Am Soc Nephrol. 2008 Sep;3(5):1504-10. doi: 10.2215/CJN.00770208. Epub 2008 May 21.
Vitamin K-dependent proteins (VKDPs) require carboxylation to become biologically active. Although the coagulant factors are the most well-known VKDPs, there are many others with important physiologic roles. Matrix Gla Protein (MGP) and Growth Arrest Specific Gene 6 (Gas-6) are two particularly important VKDPs, and their roles in vascular biology are just beginning to be understood. Both function to protect the vasculature; MGP prevents vascular calcification and Gas-6 affects vascular smooth muscle cell apoptosis and movement. Unlike the coagulant factors, which undergo hepatic carboxylation, MGP and Gas-6 are carboxylated within the vasculature. This peripheral carboxylation process is distinct from hepatic carboxylation, yet both are inhibited by warfarin administration. Warfarin prevents the activation of MGP and Gas-6, and in animals, induces vascular calcification. The relationship of warfarin to vascular calcification in humans is not fully known, yet observational data suggest an association. Given the high risk of vascular calcification in those patients with chronic kidney disease, the importance of understanding warfarin's effect on VKDPs is paramount. Furthermore, recognizing the importance of VKDPs in vascular biology will stimulate new areas of research and offer potential therapeutic interventions.
维生素K依赖性蛋白（VKDPs）需要羧化才能具有生物活性。尽管凝血因子是最广为人知的VKDPs，但还有许多其他具有重要生理作用的蛋白。基质Gla蛋白（MGP）和生长停滞特异性基因6（Gas-6）是两种特别重要的VKDPs，它们在血管生物学中的作用才刚刚开始被了解。二者都起到保护血管的作用；MGP可防止血管钙化，Gas-6则影响血管平滑肌细胞的凋亡和运动。与在肝脏进行羧化的凝血因子不同，MGP和Gas-6在血管内进行羧化。这种外周羧化过程不同于肝脏羧化，但二者都会被华法林抑制。华法林会阻止MGP和Gas-6的激活，在动物中会诱发血管钙化。华法林与人类血管钙化之间的关系尚不完全清楚，但观察数据表明存在关联。鉴于慢性肾病患者血管钙化的风险很高，了解华法林对VKDPs的影响至关重要。此外，认识到VKDPs在血管生物学中的重要性将激发新的研究领域并提供潜在的治疗干预措施。
