Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcification in experimental chronic kidney disease
Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcification in experimental chronic kidney disease
复制标题
DOI：
10.1038/ki.2012.477
复制
发表时间：
2013-05-01
影响因子：
19.6
通讯作者：
Holden, Rachel M.
中科院分区：
文献类型：
--
作者：
McCabe, Kristin M.;Booth, Sarah L.;Holden, Rachel M.
慢性肾病 (CKD) 患者死亡的主要原因是心血管疾病，其中血管钙化是疾病进展的关键调节因素。血管钙化的局部调节剂是维生素 K。这种 c-谷氨酰羧化酶底物是激活多种抑制钙化的细胞外基质蛋白的重要辅助因子。华法林是透析患者的常用疗法，可抑制维生素 K 的循环，从而降低这些蛋白质的抑制活性。在这项研究中，我们试图确定通过增加膳食维生素 K 摄入量或拮抗治疗剂量的华法林来改变维生素 K 状态是否可以改变患有腺嘌呤诱导的 CKD 的雄性 Sprague-Dawley 大鼠血管钙化的发展。华法林治疗 CKD 大鼠的脉压和脉搏波速度显着增加，胸主动脉（3 倍）、腹主动脉（8 倍）、肾动脉（4 倍）和颈动脉（20 倍）的钙浓度显着增加。相比之下，高膳食维生素 K1 治疗可增加维生素 K 组织浓度（10-300 倍）并减缓血管钙化的发展。因此，在 CKD 实验模型中，维生素 K 在改变与动脉钙化敏感性相关的机制方面具有重要作用。
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 c-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.