Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study.
Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study.
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DOI：
10.1186/1471-2369-14-219
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发表时间：
2013-10-10
期刊：
影响因子：
2.3
通讯作者：
Ketteler M
中科院分区：
文献类型：
--
作者：
Brandenburg VM;Kramann R;Koos R;Krüger T;Schurgers L;Mühlenbruch G;Hübner S;Gladziwa U;Drechsler C;Ketteler M
Sclerostin是一种Wnt通路拮抗剂，调节成骨细胞活性和骨转换。在此，我们评估了硬化蛋白与血液透析（HD）患者冠状动脉（CAC）和主动脉瓣钙化（AVC）发生的潜在相关性。我们对67例慢性HD患者（59.4 ± 14.8岁）进行了横断面多层计算机断层扫描（MS-CT）研究，以测量CAC和AVC。我们测试了已建立的生物标志物以及血清硬化素（ELISA）与钙化存在的相关性。54名无相关肾脏疾病的成人作为血清硬化蛋白水平的对照。此外，通过免疫组织化学和mRNA定量（Qt-RT-PCR）离体分析了15例透析患者的主动脉瓣硬化蛋白表达。CAC（Agatston评分> 100）和任何AVC分别存在于65%和40%的MS-CT患者组中。与对照相比，HD中的血清硬化蛋白水平（1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL，p < 0.001）显著升高，并且在具有AVC的HD患者中与不具有AVC的患者相比更是如此（1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL，p = 0.02）。AVC的多变量回归分析显示与更高的血清硬化素显著相关。尿毒症钙化主动脉瓣的离体分析（n = 10）揭示了非常接近钙化区域的强硬化蛋白表达（在非钙化瓣膜中没有硬化蛋白染色）。相应地，我们观察到与非钙化对照瓣膜相比，钙化瓣膜中sclerostin mRNA的高度显著上调。我们发现硬化蛋白与血液透析患者的钙化性主动脉瓣疾病有很强的相关性。硬化蛋白在钙化区域附近的主动脉瓣组织中局部产生。
Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 ± 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR). CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves. We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification.
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