Upregulation of Cartilage Oligomeric Matrix Protein and Bone Morphogenetic Protein-2 May Associate with Calcific Aortic Valve Disease

Yueyue Xu, Yide Cao, Yafeng Liu, Jingsong Wang, Ganyi Chen, ZhongHao Tao, Yiwei Yao, Y. Cai, Yunzhang Wu, Wen Chen
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引用次数: 1

Abstract

Abstract Objective: Calcific aortic valve disease (CAVD) affects millions of elderly people, and there is currently no effective way to stop or slow down its progression. Therefore, exploring the pathogenesis of CAVD is very important for prevention and treatment. Cartilage oligomeric matrix protein (COMP) have important role in cell phenotype change. This study is aimed to confirm whether COMP participate in CAVD and try to find the possible mechanisms. Methods: Human aortic valve tissues from Nanjing First Hospital (CAVD group, n = 20; control group, n = 11) were harvested. The expression level of COMP was tested by western blot and immunohistochemistry. Dual immunofluorescence staining was used for locating COMP. Bone morphogenetic protein-2 (BMP2) signalling were tested by western blot. The animal model was also used to detect COMP level by immunohistochemistry. Results: The results showed that the expression level of COMP was significantly increased in the calcific valve samples when compared with that of the control valve (P < 0.05); COMP was expressed near the calcific nodules and co-localized with α-smooth muscle actin (α-SMA). The protein levels of BMP2 and p-Smads 1/5/9 were markedly more highly expressed in the CAVD group than the control group (P < 0.05). Furthermore, immunofluorescence detection showed that COMP and BMP2 were co-located in calcific valves. Conclusions: The above results suggested that upregulation of COMP and BMP2 may be associated with aortic valve calcification and that COMP may become a potential therapeutic target in human CAVD.
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软骨寡聚基质蛋白和骨形态发生蛋白-2的上调可能与钙化性主动脉瓣病有关
摘要目的:钙化性主动脉瓣病(CAVD)影响着数百万老年人,目前还没有有效的方法来阻止或减缓其进展。因此,探讨CAVD的发病机制对预防和治疗具有重要意义。软骨寡聚基质蛋白(COMP)在细胞表型变化中具有重要作用。本研究旨在确认COMP是否参与CAVD,并试图寻找可能的机制。方法:取南京市第一医院人主动脉瓣组织(CAVD组 = 20;对照组,n = 11) 被收割。采用免疫组化和蛋白质印迹法检测COMP的表达水平。双免疫荧光染色定位COMP。骨形态发生蛋白2(BMP2)信号传导通过蛋白质印迹进行检测。动物模型采用免疫组织化学方法检测COMP水平。结果:与对照组相比,钙化瓣组织中COMP的表达水平明显升高(P < 0.05);COMP在钙化结节附近表达,并与α-平滑肌肌动蛋白(α-SMA)共定位。CAVD组BMP2和p-Smads1/5/9蛋白表达明显高于对照组(p < 免疫荧光检测显示COMP和BMP2位于钙化瓣膜中。结论:上述结果表明,COMP和BMP2的上调可能与主动脉瓣钙化有关,COMP可能成为人类CAVD的潜在治疗靶点。
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