Heat shock protein 90 is downregulated in calcific aortic valve disease |
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Author: | Weisell, Jonna1; Ohukainen, Pauli2; Näpänkangas, Juha3; |
Organizations: |
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 |
Format: | article |
Version: | published version |
Access: | open |
Online Access: | PDF Full Text (PDF, 3.5 MB) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe202003279474 |
Language: | English |
Published: |
Springer Nature,
2019
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Publish Date: | 2020-03-27 |
Description: |
AbstractBackground: 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. see all
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Series: |
BMC cardiovascular disorders |
ISSN: | 1471-2261 |
ISSN-E: | 1471-2261 |
ISSN-L: | 1471-2261 |
Volume: | 19 |
Issue: | 1 |
Article number: | 306 |
DOI: | 10.1186/s12872-019-01294-2 |
OADOI: | https://oadoi.org/10.1186/s12872-019-01294-2 |
Type of Publication: |
A1 Journal article – refereed |
Field of Science: |
317 Pharmacy 3111 Biomedicine |
Subjects: | |
Funding: |
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. |
Copyright information: |
© The Author(s). 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
https://creativecommons.org/licenses/by/4.0/ |