{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:48:19Z","timestamp":1789984099584,"version":"4.0.1"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The phenotypic transition of pulmonary artery smooth muscle cells (PASMCs) is a central pathological alteration in pulmonary artery remodeling, contributing to pulmonary hypertension. Super-enhancers (SEs), characterized by histone modifications and the binding of coactivators, drive the expression of prominent genes that define cellular identity. However, the specific role of SEs, particularly SE-driven lncRNAs (long noncoding RNAs), in hypoxia-induced phenotypic plasticity of PASMCs remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>In this study, the lncRNA UNC5B antisense RNA 1 (UNC5B-AS1) regulated by SEs was screened in hypoxic PASMCs using RNA sequencing and H3K27ac (histone 3 lysine 27 acetylation) ChIP (chromatin immunoprecipitation) sequencing. Overexpression or knockdown of UNC5B-AS1 in vitro was performed to elucidate its role in pulmonary hypertension pathogenesis. A serotype 5 adenovirus-associated virus carrying a conserved functional fragment of UNC5B-AS1 was used to treat pulmonary hypertension in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We identified UNC5B-AS1 as an SE-driven lncRNA transcriptionally activated by the transcription factor FOXP3 (forkhead box protein P3), which regulates phenotypic transition in PASMCs. Notably, we demonstrated that UNC5B-AS1 interacts with key glycolytic enzymes in the cytoplasm and likely serves as a molecular scaffold for LRPPRC (leucine-rich PPR motif-containing protein) and oxidative respiratory chain complex IV in mitochondria. Consequently, the deficiency of UNC5B-AS1 in PASMCs promotes the lactylation of promoter regions within inflammatory genes, including those of IL (interleukin)-1\u03b2, IL-6, and TNF-\u03b1 (tumor necrosis factor-\u03b1), under hypoxic conditions, ultimately leading to inflammatory phenotypic transition of PASMCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our findings identify SE-driven UNC5B-AS1 as a novel regulatory factor in the hypoxia-induced phenotypic transition of PASMCs and suggest that overexpression of UNC5B-AS1 may represent a promising therapeutic strategy for pulmonary hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.124.322174","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T05:00:21Z","timestamp":1746680421000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Super-Enhancer\u2013Driven LncRNA UNC5B-AS1 Inhibits Inflammatory Phenotypic Transition in Pulmonary Artery Smooth Muscle Cells via Lactylation"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8123-6480","authenticated-orcid":true,"given":"Xiangrui","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangming","family":"Pang","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy (X.W.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Guan","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Harbin Medical University, PR China (X.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaosi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-4152","authenticated-orcid":true,"given":"Lixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6103-9836","authenticated-orcid":true,"given":"Xiaodong","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Basic Medicine (F.L.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8718-6378","authenticated-orcid":true,"given":"Jian","family":"Mei","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. 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Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0937-3375","authenticated-orcid":true,"given":"Yingli","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. Zheng, J.M., L.O., Y.L., Z.M., Y.C., C.M.), Harbin Medical University (Daqing), PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8413-5284","authenticated-orcid":true,"given":"Cui","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Medical Laboratory Science and Technology (X. Zhu, X.P., Y.T., Z.W., L.Z., X. 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