@article{oai:hirosaki.repo.nii.ac.jp:00007176,
 author = {Yu, Zaiqiang and Daitoku, Kazuyuki and Fukuda, Ikuo and Imaizumi, Tadaatsu and Minakawa, Masahito and Furukawa, Ken-Ichi and Seya, Kazuhiko},
 issue = {1-4},
 journal = {弘前医学, Hirosaki Medical Journal},
 month = {Mar},
 note = {Objective: Wingless/integrase 5a（Wnt5a） pathway is known to regulate the osteogenesis. In this study, we aimed to clarify the role of Wnt5a pathway in aortic valve ectopic calcification.
Methods: Human aortic valve interstitial cells（HAVICs） were obtained from calcified aortic valves of patients with calcific aortic valve stenosis（CAVS）. HAVICs were separated to CD34-negative and -positive cells by flow cytometry. We measured real-time PCR, alkaline phosphatase（ALP） activity, Alizarin Red S staining as an index of calcification. Immunohistochemical staining was performed to confirm the distribution of Wnt5a on calcified and normal aortic valves.
Results: HAVICs, especially, CD34-negative cells are highly sensitive to tumor necrosis factor-α（ TNF-α, 30 ng/mL）, and which accelerated the Wnt5a gene expression. Wnt5a antagonist, box5, did not down-regulate HAVIC calcification induced by TNF-α. Further, Wnt5a agonist, foxy5, did not accelerated HAVIC calcification induced by TNF-α. There was no significant difference in the TNF-α-induced acceleration of ALP activity between the cells treated with foxy5 and box5. Furthermore, the proportion of Wnt5a positive cells was no difference between calcified and normal valves.
Conclusions: We confirmed that Wnt5a pathway does not regulate the TNF-α-induced aortic valve calcification in HAVICs obtained from CAVS patients.},
 pages = {20--29},
 title = {Wnt5a pathway was not involved in the progression of valve calcification in calcific aortic valve stenosis},
 volume = {73},
 year = {2023}
}