TY - JOUR
T1 - Identification of TNFα-mediated inflammation as potential pathological marker and therapeutic target for calcification progress of congenital bicuspid aortic valve
AU - Xiao, Feng
AU - Pan, Haotian
AU - Yang, Di
AU - Wang, Ruxing
AU - Wu, Bingruo
AU - Shao, Yongfeng
AU - Zhou, Bin
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/7/15
Y1 - 2023/7/15
N2 - Backgroud: Congenital bicuspid aortic valve (cBAV) develops calcification and stenotic obstruction early compared with degenerative tricuspid aortic valve (dTAV), which requires surgical intervention. Here we report a comparative study of patients with cBAV or dTAV to identify risk factors associated with the rapid development of calcified bicuspid valves. Methods: A total of 69 aortic valves (24 dTAV and 45 cBAV) were collected at the time of surgical aortic valve replacement for comparative clinical characteristics. Ten samples were randomly selected from each group for histology, pathology, and inflammatory factors expression and comparison analyses. OM-induced calcification in porcine aortic valve interstitial cell cultures were prepared for illustrating the underlying molecular mechanisms about calcification progress of cBAV and dTAV. Results: We found that cBAV patients have increased cases of aortic valve stenosis compared with dTAV patients. Histopathological examinations revealed increased collagens deposition, neovascularization and infiltrations by inflammatory cells, especially T-lymphocytes and macrophages. We identified that tumor necrosis factor α (TNFα) and its regulated inflammatory cytokines are upregulated in cBAV. Further in vitro study indicated that TNFα-NFκB and TNFα-GSK3β pathway accelerate aortic valve interstitial cells calcification, while inhibition of TNFα significantly delays this process. Conclusion: The finding of intensified TNFα-mediated inflammation in the pathological cBAV advocates the inhibition of TNFα as a potential treatment for patients with cBAV by alleviating the progress of inflammation-induced valve damage and calcification.
AB - Backgroud: Congenital bicuspid aortic valve (cBAV) develops calcification and stenotic obstruction early compared with degenerative tricuspid aortic valve (dTAV), which requires surgical intervention. Here we report a comparative study of patients with cBAV or dTAV to identify risk factors associated with the rapid development of calcified bicuspid valves. Methods: A total of 69 aortic valves (24 dTAV and 45 cBAV) were collected at the time of surgical aortic valve replacement for comparative clinical characteristics. Ten samples were randomly selected from each group for histology, pathology, and inflammatory factors expression and comparison analyses. OM-induced calcification in porcine aortic valve interstitial cell cultures were prepared for illustrating the underlying molecular mechanisms about calcification progress of cBAV and dTAV. Results: We found that cBAV patients have increased cases of aortic valve stenosis compared with dTAV patients. Histopathological examinations revealed increased collagens deposition, neovascularization and infiltrations by inflammatory cells, especially T-lymphocytes and macrophages. We identified that tumor necrosis factor α (TNFα) and its regulated inflammatory cytokines are upregulated in cBAV. Further in vitro study indicated that TNFα-NFκB and TNFα-GSK3β pathway accelerate aortic valve interstitial cells calcification, while inhibition of TNFα significantly delays this process. Conclusion: The finding of intensified TNFα-mediated inflammation in the pathological cBAV advocates the inhibition of TNFα as a potential treatment for patients with cBAV by alleviating the progress of inflammation-induced valve damage and calcification.
KW - Calcification
KW - Congenital bicuspid aortic valve
KW - Degenerative tricuspid aortic valve
KW - Inflammation
KW - Tumor necrosis factor α
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U2 - 10.1016/j.ejphar.2023.175783
DO - 10.1016/j.ejphar.2023.175783
M3 - Article
C2 - 37172927
AN - SCOPUS:85159095816
SN - 0014-2999
VL - 951
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 175783
ER -