{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:58:53Z","timestamp":1792673933653,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Obstructive sleep apnea (OSA) is strongly associated with an increased risk of hypertension; however, the molecular mechanisms linking these two conditions remain incompletely understood. In this study, we identified phosphodiesterase 4B (PDE4B) as a key mediator in the development of OSA\u2010related hypertension. Using integrated bioinformatics analysis and experimental validation, we found that PDE4B expression was significantly elevated in both cell and animal models of OSA combined with pulmonary hypertension. Functional studies demonstrated that PDE4B promotes pulmonary artery smooth muscle cell (PASMC) proliferation and migration, contributing to vascular remodelling. Mechanistically, we uncovered that lactate accumulation under hypoxic conditions induces histone lactylation at the PDE4B promoter, enhancing its transcriptional activity. Furthermore, PDE4B was shown to regulate the phosphorylation and nuclear translocation of FUS, which binds to the angiotensinogen (AGT) promoter and enhances AGT expression, thereby promoting pulmonary hypertension. These findings reveal a novel PDE4B\u2010FUS\u2010AGT signalling axis driven by epigenetic modifications in OSA\u2010induced hypertension, offering potential therapeutic targets for patients with this comorbidity.<\/jats:p>","DOI":"10.1111\/cpr.70145","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T09:58:09Z","timestamp":1763373489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>OSA<\/scp>\n                    Initiates Histone Lactylation That Drives\n                    <scp>PDE4B<\/scp>\n                    \/\n                    <scp>FUS<\/scp>\n                    \/\n                    <scp>AGT<\/scp>\n                    Axis to Pulmonary Hypertension"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6901-6703","authenticated-orcid":false,"given":"Li","family":"Yang","sequence":"first","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6698-9127","authenticated-orcid":false,"given":"Qing","family":"Ni","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6142-8856","authenticated-orcid":false,"given":"Yan","family":"He","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-6571","authenticated-orcid":false,"given":"Shijie","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7655-9703","authenticated-orcid":false,"given":"Lulu","family":"Gan","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5262-1410","authenticated-orcid":false,"given":"Anni","family":"Dai","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9289-5514","authenticated-orcid":false,"given":"Yang","family":"Hu","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7816-3744","authenticated-orcid":false,"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0522-9553","authenticated-orcid":false,"given":"Xueling","family":"Yang","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3188-6851","authenticated-orcid":false,"given":"Jiqian","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5054-1506","authenticated-orcid":false,"given":"Yi","family":"Tao","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0059-6526","authenticated-orcid":false,"given":"Yunyu","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2255-3273","authenticated-orcid":false,"given":"Mingyue","family":"Xu","sequence":"additional","affiliation":[{"name":"The Affiliated Yan\u2019an Hospital of Kunming Medical University Kunming Hypertension Center  Kunming City China"},{"name":"Kunming Technical Diagnosis and Treatment Center for Refractory Hypertension  Kunming City China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.3514"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02258\u20102020"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010023\u201000846\u20106"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41440\u2010023\u201001320\u2010z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137560"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/234631"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00234\u20102016"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010019\u20100132\u20106"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1614"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116331"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjac073"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1268646"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.12.008"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.114095"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.01.012"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.06.023"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.09.023"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100227\u2010y"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.013"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101678\u20101"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16332"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40104\u2010024\u201001045\u20100"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae136"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12050817"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2023.01.008"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0206\u20102022"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2201737"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02308\u20102018"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202009\u20103419OC"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14091894"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.12.020"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.12.011"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101765"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201002008\u20109"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae407"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.276725"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311817"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.220"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.12.005"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf8660"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.70145","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.70145","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.70145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T13:47:01Z","timestamp":1777729621000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.70145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/cpr.70145"],"URL":"https:\/\/doi.org\/10.1111\/cpr.70145","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]},"assertion":[{"value":"2025-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70145"}}