Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Kidney Int. 2013 May;83(5):835-44. doi: 10.1038/ki.2012.477. Epub 2013 Jan 23.
The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease, with vascular calcification being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This γ-glutamyl carboxylase substrate is an essential cofactor in the activation of several extracellular matrix proteins that inhibit calcification. Warfarin, a common therapy in dialysis patients, inhibits the recycling of vitamin K and thereby decreases the inhibitory activity of these proteins. In this study, we sought to determine whether modifying vitamin K status, either by increasing dietary vitamin K intake or by antagonism with therapeutic doses of warfarin, could alter the development of vascular calcification in male Sprague-Dawley rats with adenine-induced CKD. Treatment of CKD rats with warfarin markedly increased pulse pressure and pulse wave velocity, as well as significantly increased calcium concentrations in the thoracic aorta (3-fold), abdominal aorta (8-fold), renal artery (4-fold), and carotid artery (20-fold). In contrast, treatment with high dietary vitamin K1 increased vitamin K tissue concentrations (10-300-fold) and blunted the development of vascular calcification. Thus, vitamin K has an important role in modifying mechanisms linked to the susceptibility of arteries to calcify in an experimental model of CKD.
慢性肾脏病 (CKD) 患者的主要死亡原因是心血管疾病，血管钙化是疾病进展的关键调节剂。血管钙化的局部调节剂是维生素 K。这种 γ-谷氨酰羧化酶底物是几种细胞外基质蛋白激活的必需辅助因子，这些蛋白可抑制钙化。华法林是透析患者的常用疗法，它抑制了维生素 K 的再循环，从而降低了这些蛋白的抑制活性。在这项研究中，我们试图确定通过增加膳食维生素 K 摄入或用治疗剂量的华法林拮抗来改变维生素 K 状态是否可以改变腺嘌呤诱导的 CKD 雄性 Sprague-Dawley 大鼠的血管钙化发展。用华法林治疗 CKD 大鼠显著增加了脉搏压和脉搏波速度，并且显著增加了胸主动脉（3 倍）、腹主动脉（8 倍）、肾动脉（4 倍）和颈动脉（20 倍）中的钙浓度。相比之下，用高膳食维生素 K1 治疗可增加维生素 K 组织浓度（10-300 倍）并抑制血管钙化的发展。因此，维生素 K 在修饰与 CKD 实验模型中动脉易发生钙化相关的机制方面具有重要作用。
