Heat shock protein 90 is downregulated in calcific aortic valve disease

• Main Authors: Jonna Weisell, Pauli Ohukainen, Juha Näpänkangas, Steffen Ohlmeier, Ulrich Bergmann, Tuomas Peltonen, Panu Taskinen, Heikki Ruskoaho, Jaana Rysä
• Format: Article
• Language: English
• Published: BMC 2019-12-01
• Series: BMC Cardiovascular Disorders
• Subjects: Aortic valve stenosis; Calcified aortic valve disease; Heat-shock protein; Proteomics
• Online Access: https://doi.org/10.1186/s12872-019-01294-2

Abstract 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.