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
Heat shock protein 90 is downregulated in calcific aortic valve disease
|Author:||Weisell, Jonna1; Ohukainen, Pauli2; Näpänkangas, Juha3;|
1School of Pharmacy, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland
2Research Unit of Biomedicine, Computational Medicine, University of Oulu, Oulu, Finland
3Department of Pathology, Cancer Research and Translational Medicine Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland
4Proteomics and Mass Spectrometry Core Facilities, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
5Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
6Department of Cardiovascular Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
7Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
8Drug Research Program and Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland
|Online Access:||PDF Full Text (PDF, 3.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202003279474
|Publish Date:|| 2020-03-27
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.
BMC cardiovascular disorders
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by grants from the Academy of Finland (Center of Excellence Funding and grants 266661, 276747 and 284504), the Sigrid Jusélius Foundation, the Päivikki and the Sakari Sohlberg Foundation, the Paavo Nurmi Foundation, the Ida Montin Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, the Aarne Koskelo Foundation and the Orion Research Foundation. None of the funders had role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
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