Heat shock protein 90 is downregulated in calcific aortic valve disease
Weisell, Jonna; Ohukainen, Pauli; Näpänkangas, Juha; Ohlmeier, Steffen; Ulrich Bergmann, Ulrich; Peltonen, Tuomas; Taskinen, Panu; Ruskoaho, Heikki; Rysä, Jaana (2019-12-19)
Weisell, J., Ohukainen, P., Näpänkangas, J. et al. Heat shock protein 90 is downregulated in calcific aortic valve disease. BMC Cardiovasc Disord 19, 306 (2019). https://doi.org/10.1186/s12872-019-01294-2
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https://urn.fi/URN:NBN:fi-fe202003279474
Tiivistelmä
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.
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