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In vivo, two models of aortic valve stenosis were constructed by ascending aortic constriction (AAC) and direct wire injury (DWI). Inhibition of Piezo1 and GLS1 in these models respectively mitigated aortic valve lesion. In vitro, Piezo1 activation induced by Yoda1 and oscillatory stress triggered osteogenic responses in VICs, which were prevented by Piezo1 inhibition or knockdown. Mechanistically, Piezo1 activation promoted calcium-dependent Yes-associated protein (YAP) activation. YAP modulated GLS1-mediated glutaminolysis, which enhanced osteogenic differentiation through histone acetylation of runt-related transcription factor 2 (RUNX2) promoters. Together, our work provided a cross-talk between mechanotransduction and metabolism in the context of CAVD.<\/jats:p>","DOI":"10.1126\/sciadv.adg0478","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T13:58:43Z","timestamp":1685714323000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":129,"title":["Activation of Piezo1 promotes osteogenic differentiation of aortic valve interstitial cell through YAP-dependent glutaminolysis"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-8372","authenticated-orcid":true,"given":"Guoheng","family":"Zhong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China."},{"name":"Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou 510515, 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