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Differential proteome profile, biological pathways, and network relationships of osteogenic proteins in calcified human aortic valves.

Authors :
Han RI
Hu CW
Loose DS
Yang L
Li L
Connell JP
Reardon MJ
Lawrie GM
Qutub AA
Morrisett JD
Grande-Allen KJ
Source :
Heart and vessels [Heart Vessels] 2022 Feb; Vol. 37 (2), pp. 347-358. Date of Electronic Publication: 2021 Nov 02.
Publication Year :
2022

Abstract

Calcific aortic valve disease (CAVD) is the most common heart valve disease requiring intervention. Most research on CAVD has focused on inflammation, ossification, and cellular phenotype transformation. To gain a broader picture into the wide range of cellular and molecular mechanisms involved in this disease, we compared the total protein profiles between calcified and non-calcified areas from 5 human valves resected during surgery. The 1413 positively identified proteins were filtered down to 248 proteins present in both calcified and non-calcified segments of at least 3 of the 5 valves, which were then analyzed using Ingenuity Pathway Analysis. Concurrently, the top 40 differentially abundant proteins were grouped according to their biological functions and shown in interactive networks. Finally, the abundance of selected osteogenic proteins (osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK) was quantified using ELISA and/or immunohistochemistry. The top pathways identified were complement system, acute phase response signaling, metabolism, LXR/RXR and FXR/RXR activation, actin cytoskeleton, mineral binding, nucleic acid interaction, structural extracellular matrix (ECM), and angiogenesis. There was a greater abundance of osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK in the calcified regions than the non-calcified ones. The osteogenic proteins also formed key connections between the biological signaling pathways in the network model. In conclusion, this proteomic analysis demonstrated the involvement of multiple signaling pathways in CAVD. The interconnectedness of these pathways provides new insights for the treatment of this disease.<br /> (© 2021. Springer Japan KK, part of Springer Nature.)

Details

Language :
English
ISSN :
1615-2573
Volume :
37
Issue :
2
Database :
MEDLINE
Journal :
Heart and vessels
Publication Type :
Academic Journal
Accession number :
34727208
Full Text :
https://doi.org/10.1007/s00380-021-01975-z