Journal article
Osteopontin alters endothelial and valvular interstitial cell behaviour in calcific aortic valve stenosis through HMGB1 regulation
European Journal of Cardio-Thoracic Surgery, Vol.48(3), pp.e20-e29
2015
Abstract
OBJECTIVES: Calcific aortic valve stenosis (CAVS) is an important clinical problem predominantly affecting elderly individuals. Studies suggest that the progression of CAVS is actively regulated with valve endothelial injury leading to inflammation, fibrosis and calcification. The aim of this study was to delineate the possible regulatory role of osteopontin (OPN) on high-mobility group box 1 (HMGB1) function and the associated inflammatory and fibrotic response in CAVS. METHODS: Aortic valve leaflets were collected from CAVS patients undergoing aortic valve replacement (n = 40), and control aortic valve leaflets were obtained from heart transplant recipients (n = 15). Valves and plasma were analysed by quantitative real-time polymerase chain reaction (PCR), immunohistochemical staining and Western blot. Recombinant OPN or neutralizing OPN antibody was added to cultured endothelial and valvular interstitial cells (VICs), and cell proliferation scores and HMGB1 expression were assessed. RESULTS: CAVS valves had a decreased total percentage of VICs but increased numbers of infiltrating macrophages relative to control valves. RT-PCR studies showed higher expression of OPN, the inflammatory cytokine tumour necrosis factor-alpha as well as markers of fibrosis, tissue inhibitor of matrix metalloproteinase 1 and matrix metalloproteinase 2 in CAVS valves. Elevated expression of OPN was also observed in plasma of CAVS patients compared with controls. HMGB1 was detected in the secretory granules of cultured valve endothelial and VICs derived from CAVS valves. The addition of exogenous OPN inhibited the proliferation of cultured endothelial and VICs from CAVS valves and was associated with the extracellular expression of HMGB1, whereas neutralizing OPN had the opposite effect. CONCLUSIONS: We conclude that altered OPN expression in CAVS affects cellular HMGB1 function inducing cytoplasmic translocation and secretion of HMGB1 in endothelial cells and VICs, thus indicating a regulatory role for OPN in the progression of CAVS through alteration of HMGB1 function.
Details
- Title
- Osteopontin alters endothelial and valvular interstitial cell behaviour in calcific aortic valve stenosis through HMGB1 regulation
- Authors
- Margaret Passmore (Author) - University of QueenslandMaria Nataatmadja (Author) - University of QueenslandYoke Lin Fung (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and EngineeringBronwyn Louise Pearse (Author) - Prince Charles HospitalSarah Gabriel (Author) - Prince Charles HospitalPeter Tesar (Author) - Prince Charles HospitalJohn F Fraser (Author) - University of Queensland
- Publication details
- European Journal of Cardio-Thoracic Surgery, Vol.48(3), pp.e20-e29
- Publisher
- Oxford University Press
- Date published
- 2015
- DOI
- 10.1093/ejcts/ezv244
- ISSN
- 1010-7940
- Copyright note
- Copyright © 2015 The Author. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99449923002621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Cardiac & Cardiovascular Systems
- Respiratory System
- Surgery
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