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血管钙化中骨相关蛋白的表达及其与冠状动脉钙化积分的血清相关性。

Expression of bone-related proteins in vascular calcification and its serum correlations with coronary artery calcification score.

机构信息

Department of Surgery, University Hospital Rijeka, Rijeka, Croatia.

Department of Radiology, University Hospital Rijeka, Rijeka, Croatia.

出版信息

J Biol Regul Homeost Agents. 2019;33(1):29-38.

Abstract

Since vascular calcification is considered a process regulated similar to that of bone tissue mineralization, we investigated the participation of bone formation proteins. We analyzed the correlation of serum circulating bone markers, osteoprotegerin (OPG) and receptor activator of nuclear factor ĸB ligand (RANKL) in chronic kidney disease (CKD) patients, to coronary artery calcification score. We also considered the effect of inorganic phosphate on pro- and anti-calcifying tissue factors. We confirmed that circulating OPG is an independent calcium score predictor with its high serum concentration favoring high coronary artery calcification. In tissue samples of non-diseased human renal arteries, the expression of OPG and receptor activator of nuclear factor ĸB (RANK) was positive, while expression of RANKL was absent. In atherosclerotic specimens and arteries with medial calcification, the most upregulated was expression of bone morphogenetic proteins, BMP-2 and BMP-7, as well as expression of RANK and RANKL. In the diseased arteries, OPG expression was present only in areas where bone structures were formed. In atherosclerotic and medial calcification arteries, loss of alpha-smooth muscle actin (α-SMA) expression was observed. These data suggest a possible regulatory role of the examined proteins, especially OPG and RANKL, in vascular calcification, as well as their possible clinical significance as circulating predictors of vascular calcification.

摘要

由于血管钙化被认为是类似于骨组织矿化的过程受到调节,我们研究了骨形成蛋白的参与。我们分析了血清循环骨标志物、骨保护素 (OPG) 和核因子 κB 受体激活剂配体 (RANKL) 在慢性肾脏病 (CKD) 患者中的相关性,以评估其与冠状动脉钙化评分的关系。我们还考虑了无机磷酸盐对促钙化和抗钙化组织因子的影响。我们证实,循环 OPG 是钙评分的独立预测因子,其高血清浓度有利于冠状动脉钙化。在非病变人类肾动脉的组织样本中,OPG 和核因子 κB 受体激活剂 (RANK) 的表达呈阳性,而 RANKL 的表达则不存在。在动脉粥样硬化标本和中层钙化的动脉中,骨形态发生蛋白 BMP-2 和 BMP-7 以及 RANK 和 RANKL 的表达上调最为明显。在病变的动脉中,仅在形成骨结构的区域观察到 OPG 表达。在动脉粥样硬化和中层钙化的动脉中,观察到α-平滑肌肌动蛋白 (α-SMA)表达的丧失。这些数据表明,所研究的蛋白质,特别是 OPG 和 RANKL,可能在血管钙化中具有调节作用,并且它们作为血管钙化的循环预测因子具有潜在的临床意义。

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