{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:27:38Z","timestamp":1791203258239,"version":"4.2.0"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General Program of the Chongqing Natural Science Foundation","award":["CSTB2025NSCQ-GPX0377"],"award-info":[{"award-number":["CSTB2025NSCQ-GPX0377"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["GZC20251459"],"award-info":[{"award-number":["GZC20251459"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300529"],"award-info":[{"award-number":["82300529"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elevated plasma lactate is a significant risk factor in pulmonary hypertension (PH), and endothelial-mesenchymal transition (EndoMT) is a major contributor to this pathological process, yet its specific role in driving endothelial-mesenchymal transition (EndoMT) remains unclear. Using in vivo and in vitro models, we demonstrate that modulating lactate levels critically influences PH progression. In a hypoxic PH mouse model, inhibition of lactate production ameliorated hemodynamic and vascular remodeling, whereas exogenous lactate exacerbated these pathologies. In human pulmonary arterial endothelial cells under hypoxia, lactate promoted a pro-remodeling phenotype, enhancing migration, proliferation, and EndoMT. Mechanistically, lactate induced Twist1 lactylation via enhanced association with p300\/CBP, promoting its nuclear translocation. This upregulated TGFB1 transcription and activated the Smad2 pathway, thereby driving EndoMT\u2014an effect abolished by Twist1 knockdown. Our findings reveal a previously unrecognized lactate-Twist1 lactylation-TGFB1 axis that promotes vascular remodeling in PH, identifying novel therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms27052255","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:52:38Z","timestamp":1772207558000},"page":"2255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lactate Promotes Endothelial-Mesenchymal Transition via Mediating Twist1 Lactylation in Hypoxic Pulmonary Hypertension"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0620-9175","authenticated-orcid":false,"given":"Xingbing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Military Medical University, Chongqing 400042, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8460-2569","authenticated-orcid":false,"given":"Ningxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biological Engineering, Chongqing University of Technology, Chongqing 400054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Yu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4787-8135","authenticated-orcid":false,"given":"Ming","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-023-00486-7","article-title":"Pulmonary hypertension","volume":"10","author":"Mocumbi","year":"2024","journal-title":"Nat. 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