TY - JOUR
T1 - Differential proteome profile, biological pathways, and network relationships of osteogenic proteins in calcified human aortic valves
AU - Han, Richard I.
AU - Hu, Chenyue W.
AU - Loose, David S.
AU - Yang, Li
AU - Li, Li
AU - Connell, Jennifer P.
AU - Reardon, Michael J.
AU - Lawrie, Gerald M.
AU - Qutub, Amina A.
AU - Morrisett, Joel D.
AU - Grande-Allen, K. Jane
N1 - Publisher Copyright:
© 2021, Springer Japan KK, part of Springer Nature.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Aortic valve
KW - Calcification
KW - Pathways
KW - Proteomics
KW - Aortic Valve/metabolism
KW - Osteogenesis/physiology
KW - Humans
KW - Aortic Valve Stenosis/metabolism
KW - Calcinosis/metabolism
KW - Proteome/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85118369284&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118369284&partnerID=8YFLogxK
U2 - 10.1007/s00380-021-01975-z
DO - 10.1007/s00380-021-01975-z
M3 - Article
C2 - 34727208
AN - SCOPUS:85118369284
SN - 0910-8327
VL - 37
SP - 347
EP - 358
JO - Heart and Vessels
JF - Heart and Vessels
IS - 2
ER -