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Open AccessArticle

Proteoglycan 4 is Increased in Human Calcified Aortic Valves and Enhances Valvular Interstitial Cell Calcification

1
Department of Medicine, Karolinska Institutet, 17177 Stockholm, Sweden
2
Department of Molecular Medicine and Surgery, Karolinska Institutet, 17177 Stockholm, Sweden
3
Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, 17177 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
International Network for Training on Risks of Vascular Intimal Calcification and roads to Regression of Cardiovascular Disease (INTRICARE).
Cells 2020, 9(3), 684; https://doi.org/10.3390/cells9030684
Received: 22 January 2020 / Revised: 7 March 2020 / Accepted: 9 March 2020 / Published: 11 March 2020
(This article belongs to the Special Issue The Molecular and Cellular Basis of Cardiovascular Disease)
Aortic valve stenosis (AVS), a consequence of increased fibrosis and calcification of the aortic valve leaflets, causes progressive narrowing of the aortic valve. Proteoglycans, structural components of the aortic valve, accumulate in regions with fibrosis and moderate calcification. Particularly, proteoglycan 4 (PRG4) has been identified in fibrotic parts of aortic valves. However, the role of PRG4 in the context of AVS and aortic valve calcification has not yet been determined. Here, transcriptomics, histology, and immunohistochemistry were performed in human aortic valves from patients undergoing aortic valve replacement. Human valve interstitial cells (VICs) were used for calcification experiments and RNA expression analysis. PRG4 was significantly upregulated in thickened and calcified regions of aortic valves compared with healthy regions. In addition, mRNA levels of PRG4 positively associated with mRNA for proteins involved in cardiovascular calcification. Treatment of VICs with recombinant human PRG4 enhanced phosphate-induced calcification and increased the mRNA expression of bone morphogenetic protein 2 and the runt-related transcription factor 2. In summary, PRG4 was upregulated in the development of AVS and promoted VIC osteogenic differentiation and calcification. These results suggest that an altered valve leaflet proteoglycan composition may play a role in the progression of AVS. View Full-Text
Keywords: proteoglycan 4; aortic valve stenosis; calcification proteoglycan 4; aortic valve stenosis; calcification
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MDPI and ACS Style

Artiach, G.; Carracedo, M.; Seime, T.; Plunde, O.; Laguna-Fernandez, A.; Matic, L.; Franco-Cereceda, A.; Bäck, M. Proteoglycan 4 is Increased in Human Calcified Aortic Valves and Enhances Valvular Interstitial Cell Calcification. Cells 2020, 9, 684. https://doi.org/10.3390/cells9030684

AMA Style

Artiach G, Carracedo M, Seime T, Plunde O, Laguna-Fernandez A, Matic L, Franco-Cereceda A, Bäck M. Proteoglycan 4 is Increased in Human Calcified Aortic Valves and Enhances Valvular Interstitial Cell Calcification. Cells. 2020; 9(3):684. https://doi.org/10.3390/cells9030684

Chicago/Turabian Style

Artiach, Gonzalo; Carracedo, Miguel; Seime, Till; Plunde, Oscar; Laguna-Fernandez, Andres; Matic, Ljubica; Franco-Cereceda, Anders; Bäck, Magnus. 2020. "Proteoglycan 4 is Increased in Human Calcified Aortic Valves and Enhances Valvular Interstitial Cell Calcification" Cells 9, no. 3: 684. https://doi.org/10.3390/cells9030684

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