Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD)
Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD)
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DOI：
10.1111/j.1523-1755.2005.00333.x
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发表时间：
2005-06-01
影响因子：
19.6
通讯作者：
Chen, NX
中科院分区：
文献类型：
--
作者：
Moe, SM;Reslerova, M;Chen, NX
背景大多数慢性肾脏病（CKD）患者存在过度的血管钙化;然而，大多数研究表明，尽管暴露于尿毒症环境相似，但一部分CKD患者没有血管钙化，也不会发生血管钙化。这表明钙化的保护机制或天然存在的抑制剂可能是重要的。为了确定胎球蛋白A、基质玻璃蛋白（MGP）和骨保护素（OPG）这三种抑制剂在CKD-5患者血管钙化中的作用，我们（1）测量了这些抑制剂的血清水平，并将其与计算机断层扫描（CT）评估的钙化水平进行比较;（2）通过对这些抑制剂的免疫染色来检查来自CKD-5患者的动脉，和（3）检查这些抑制剂在培养的牛血管平滑肌细胞（BVSMC）中的表达和作用。与健康对照组相比，尿毒症患者血清中孵育。冠状动脉钙化积分与血清胎球蛋白A水平呈负相关（r =-0.30，P = 0.034），与OPG水平呈正相关（r = 0.29，P = 0.045）。半定量钙化程度越高的动脉，胎球蛋白A和MGP的免疫染色越强（P < 0.003）。在体外，胎球蛋白-A加入到矿化的BVSMCs中抑制矿化（P < 0.001）。与正常血清相比，尿毒症血清培养的BVSMCs中MGP表达随矿化程度的增加而增加（P < 0.001），OPG表达随矿化程度的增加而增加（P < 0.04）。这些数据表明，胎球蛋白-A，OPG和MGP在尿毒症血管钙化的发病机制中发挥重要作用。
Background. The majority of patients with chronic kidney disease (CKD) have excessive vascular calcification; however, most studies demonstrate that a subset of CKD patients do not have, nor develop, vascular calcification despite similar exposure to the uremic environment. This suggests protective mechanisms, or naturally occurring inhibitors, of calcification may be important.Methods. In order to determine the role of three inhibitors, fetuin-A, matrix gla protein (MGP), and osteoprotegerin (OPG) in the vascular calcification observed in patients with CKD-5, we (1) measured serum levels of these inhibitors and compared the levels to calcification assessed by computed tomography (CT); (2) examined arteries from CKD-5 patients by immunostaining for these inhibitors and (3) examined the expression and effect of these inhibitors in cultured bovine vascular smooth muscle cells (BVSMCs) incubated in serum pooled from uremic patients compared to healthy controls.Results. There was a negative correlation of coronary artery calcification scores with serum fetuin-A levels (r = -0.30, P = 0.034) and a positive association with OPG levels (r = 0.29, P = 0.045). There was increasing immunostaining for both fetuin-A and MGP in arteries with increasing calcification graded semiquantitatively (P < 0.003). In vitro, fetuin-A added to mineralizing BVSMCs inhibited mineralization (P < 0.001). Compared to normal serum, BVSMCs incubated with uremic serum had a progressive increase in MGP expression with mineralization (P < 0.001) and increased expression of OPG in BVSMCs (P < 0.04).Conclusion. These data demonstrate that fetuin-A, OPG, and MGP play an important role in the pathogenesis of uremic vascular calcification.