BACKGROUND Calcific aortic valve disease (CAVD) is an atheroinflammatory process; finally it leads to progressive calcification of the valve. There is no effective pharmacological treatment for CAVD and many of the underlying molecular mechanisms remain unknown. We conducted a proteomic study to reveal novel factors associated with CAVD. METHODS We compared aortic valves from patients undergoing valvular replacement surgery due to non-calcified aortic insufficiency (control group, n = 5) to a stenotic group (n = 7) using two-dimensional difference gel electrophoresis (2D-DIGE). Protein spots were identified with mass spectrometry. Western blot and immunohistochemistry were used to validate the results in a separate patient cohort and Ingenuity Pathway Analysis (IPA) was exploited to predict the regulatory network of CAVD. RESULTS We detected an upregulation of complement 9 (C9), serum amyloid P-component (APCS) and transgelin as well as downregulation of heat shock protein (HSP90), protein disulfide isomerase A3 (PDIA3), annexin A2 (ANXA2) and galectin-1 in patients with aortic valve stenosis. The decreased protein expression of HSP90 was confirmed with Western blot. CONCLUSIONS We describe here a novel data set of proteomic changes associated with CAVD, including downregulation of the pro-inflammatory cytosolic protein, HSP90.

中文翻译：

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在钙化主动脉瓣疾病中，热休克蛋白90被下调。

背景技术钙化性主动脉瓣疾病（CAVD）是一种动脉粥样硬化过程。最终导致阀门逐渐钙化。没有有效的药物治疗CAVD，许多潜在的分子机制仍然未知。我们进行了蛋白质组学研究，以揭示与CAVD相关的新因素。方法我们使用二维差值凝胶电泳（2D-DIGE），将因非钙化主动脉供血不足而进行瓣膜置换手术的患者（对照组，n = 5）与狭窄组（n = 7）进行比较。蛋白质斑点通过质谱鉴定。Western blot和免疫组化被用于验证单独患者队列中的结果，并利用了机能途径分析（IPA）来预测CAVD的调节网络。结果我们检测到补体9（C9），血清淀粉样蛋白P组分（APCS）和转蛋白的上调，以及热休克蛋白（HSP90），蛋白二硫键异构酶A3（PDIA3），膜联蛋白A2（ANXA2）和半乳糖凝集素1.主动脉瓣狭窄的患者。Western blot证实HSP90蛋白表达降低。结论我们在这里描述了与CAVD相关的蛋白质组学变化的新数据集，包括下调促炎性胞质蛋白HSP90。