{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:35:02Z","timestamp":1782448502551,"version":"3.54.5"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL157100"],"award-info":[{"award-number":["1R01HL157100"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL135810"],"award-info":[{"award-number":["1R01HL135810"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01HL178085-01A1"],"award-info":[{"award-number":["1R01HL178085-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R03TR005085-01A1"],"award-info":[{"award-number":["1R03TR005085-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Br. J. Biomed. Sci."],"abstract":"<jats:p>Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need to understand the pathophysiology of RV failure and to identify the differences between adaptive and maladaptive RV remodeling. This study analyzes changes in polyadenylation site usage, a process known as alternative polyadenylation (APA), in RV failure. APA is a mechanism used to regulate mRNA maturation that can result in either shortening or elongation of the mRNA 3\u2019UTR. By analyzing APA patterns in RV tissue from donor controls and patients with compensated and decompensated RV failure, we demonstrate a pattern of 3\u2019UTR elongation that is present in decompensated RV failure and not in compensated or control RVs. Further, altered APA was also detected in 3 distinct rat models of PH, where 15 transcripts had shared APA alterations across both rat models and human disease. Our study provides an unbiased approach to identifying the molecular changes leading to RV dysfunction while pinpointing novel therapeutic targets that can be leveraged for intervention. These APA signatures may serve as biomarkers to distinguish adaptive from maladaptive RV remodeling. In addition, the RNA-processing machinery that regulates APA, such as NUDT21 and CPSF6, represents potential therapeutic targets for RNA-based interventions. Together, our findings link RNA processing to diagnostic and therapeutic opportunities in right heart failure.<\/jats:p>","DOI":"10.3389\/bjbs.2026.15687","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:10:27Z","timestamp":1771567827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling in Pulmonary Hypertension: Implications for RNA-Based Diagnostics and Therapeutics"],"prefix":"10.3389","volume":"83","author":[{"given":"Janani","family":"Subramaniam","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata","family":"Jonnakuti","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Collum","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Martineau","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec (IUCPQ), Universit\u00e9 de Laval","place":["Qu\u00e9bec, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Lieh","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of Rochester Medical Center","place":["Rochester, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Breuils-Bonnet","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec (IUCPQ), Universit\u00e9 de Laval","place":["Qu\u00e9bec, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Frump","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine","place":["Indianapolis, IN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu H.","family":"Akkanti","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayeshkumar A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish K.","family":"Patel","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Salas de Armas","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella N.","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajko","family":"Radovancevic","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvin","family":"Blanco","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine, Houston Methodist Research Institute","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of Rochester Medical Center","place":["Rochester, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Gregoric","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sriram","family":"Nathan","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswajit","family":"Kar","sequence":"additional","affiliation":[{"name":"Center for Advanced Cardiopulmonary Therapies and Transplantation, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steeve","family":"Provencher","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec (IUCPQ), Universit\u00e9 de Laval","place":["Qu\u00e9bec, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec (IUCPQ), Universit\u00e9 de Laval","place":["Qu\u00e9bec, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Potus","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec (IUCPQ), Universit\u00e9 de Laval","place":["Qu\u00e9bec, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari Krishna","family":"Yalamanchili","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital","place":["Houston, TX, United States"]},{"name":"USDA\/ARS Children\u2019s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Karmouty-Quintana","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1093\/eurheartj\/ehl477","article-title":"Prognostic Value of Right Ventricular Mass, Volume, and Function in Idiopathic Pulmonary Arterial Hypertension","volume":"28","author":"van Wolferen","year":"2007","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1161\/CIRCRESAHA.118.313650","article-title":"Medical Therapy for Heart Failure Associated with Pulmonary Hypertension","volume":"124","author":"Zelt","year":"2019","journal-title":"Circ Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1136\/hrt.2008.156265","article-title":"Latest Insights in Therapeutic Options for Systemic Right Ventricular Failure: A Comparison With Left Ventricular Failure","volume":"95","author":"Winter","year":"2009","journal-title":"Heart"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1164\/rccm.201311-2025LE","article-title":"Treatment of Group I Pulmonary Arterial Hypertension With Carvedilol Is Safe","volume":"189","author":"Grinnan","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.jcmg.2021.07.027","article-title":"The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension","volume":"15","author":"Vonk Noordegraaf","year":"2022","journal-title":"JACC Cardiovasc Imaging"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e011227","DOI":"10.1161\/CIRCHEARTFAILURE.123.011227","article-title":"SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension","volume":"17","author":"Waxman","year":"2024","journal-title":"Circ Heart Fail"},{"key":"B7","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.jacc.2016.10.047","article-title":"The Relationship Between the Right Ventricle and Its Load in Pulmonary Hypertension","volume":"69","author":"Vonk Noordegraaf","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1067\/mtc.2002.124234","article-title":"Reversible Pulmonary Trunk Banding. II. An Experimental Model for Rapid Pulmonary Ventricular Hypertrophy","volume":"124","author":"Dias","year":"2002","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B9","doi-asserted-by":"publisher","first-page":"D22","DOI":"10.1016\/j.jacc.2013.10.027","article-title":"Right Heart Adaptation to Pulmonary Arterial Hypertension: Physiology and Pathobiology","volume":"62","author":"Vonk-Noordegraaf","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1378\/chest.08-0492","article-title":"The Right Ventricle Under Pressure: Cellular and Molecular Mechanisms of Right-Heart Failure in Pulmonary Hypertension","volume":"135","author":"Bogaard","year":"2009","journal-title":"Chest"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1161\/CIRCULATIONAHA.109.883843","article-title":"Chronic Pulmonary Artery Pressure Elevation Is Insufficient to Explain Right Heart Failure","volume":"120","author":"Bogaard","year":"2009","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1161\/CIRCRESAHA.113.301129","article-title":"The Right Ventricle in Pulmonary Arterial Hypertension: Disorders of Metabolism, Angiogenesis and Adrenergic Signaling in Right Ventricular Failure","volume":"115","author":"Ryan","year":"2014","journal-title":"Circ Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1038\/cr.2017.87","article-title":"Cardiotrophin 1 Stimulates Beneficial Myogenic and Vascular Remodeling of the Heart","volume":"27","author":"Abdul-Ghani","year":"2017","journal-title":"Cell Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1093\/cvr\/cvy258","article-title":"Fischer Rats Exhibit Maladaptive Structural and Molecular Right Ventricular Remodelling in Severe Pulmonary Hypertension: A Genetically Prone Model for Right Heart Failure","volume":"115","author":"Suen","year":"2019","journal-title":"Cardiovasc Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"L873","DOI":"10.1152\/ajplung.00006.2015","article-title":"Estradiol Improves Right Ventricular Function in Rats With Severe Angioproliferative Pulmonary Hypertension: Effects of Endogenous and Exogenous Sex Hormones","volume":"308","author":"Frump","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1164\/rccm.201003-0335OC","article-title":"Adrenergic Receptor Blockade Reverses Right Heart Remodeling and Dysfunction in Pulmonary Hypertensive Rats","volume":"182","author":"Bogaard","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1093\/cvr\/cvx148","article-title":"Treatment Strategies for the Right Heart in Pulmonary Hypertension","volume":"113","author":"Westerhof","year":"2017","journal-title":"Cardiovasc Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"17136","DOI":"10.1038\/s41598-021-96618-8","article-title":"Right Versus Left Ventricular Remodeling in Heart Failure due to Chronic Volume Overload","volume":"11","author":"Havlenova","year":"2021","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"14351","DOI":"10.1038\/s41598-020-71264-8","article-title":"Myocardial Proteomic Profile in Pulmonary Arterial Hypertension","volume":"10","author":"Ho\u0142da","year":"2020","journal-title":"Sci Rep"},{"key":"B20","doi-asserted-by":"publisher","first-page":"7104","DOI":"10.1038\/s41467-021-27326-0","article-title":"Biological Heterogeneity in Idiopathic Pulmonary Arterial Hypertension Identified Through Unsupervised Transcriptomic Profiling of Whole Blood","volume":"12","author":"Kariotis","year":"2021","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/s44161-023-00338-3","article-title":"Transcriptional Profiling Unveils Molecular Subgroups of Adaptive and Maladaptive Right Ventricular Remodeling in Pulmonary Hypertension","volume":"2","author":"Khassafi","year":"2023","journal-title":"Nat Cardiovasc Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e007058","DOI":"10.1161\/CIRCHEARTFAILURE.120.007058","article-title":"Transcriptomic Analysis of Right Ventricular Remodeling in Two Rat Models of Pulmonary Hypertension: Identification and Validation of Epithelial-To-Mesenchymal Transition in Human Right Ventricular Failure","volume":"14","author":"Park","year":"2021","journal-title":"Circ Heart Fail"},{"key":"B23","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S2213-2600(17)30161-3","article-title":"Plasma Proteome Analysis in Patients with Pulmonary Arterial Hypertension: An Observational Cohort Study","volume":"5","author":"Rhodes","year":"2017","journal-title":"Lancet Respir Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1128\/MMBR.63.2.446-456.1999","article-title":"Cytoplasmic Polyadenylation in Development and Beyond","volume":"63","author":"Richter","year":"1999","journal-title":"Microbiol Mol Biol Rev"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1093\/cvr\/cvad014","article-title":"Alternative Polyadenylation Regulation in Cardiac Development and Cardiovascular Disease","volume":"119","author":"Cao","year":"2023","journal-title":"Cardiovasc Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.molcel.2011.08.017","article-title":"Mechanisms and Consequences of Alternative Polyadenylation","volume":"43","author":"Di Giammartino","year":"2011","journal-title":"Mol Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/263211a0","article-title":"3' Non-coding Region Sequences in Eukaryotic Messenger RNA","volume":"263","author":"Proudfoot","year":"1976","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.molcel.2014.02.013","article-title":"Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting","volume":"53","author":"Nam","year":"2014","journal-title":"Mol Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nrm.2016.116","article-title":"Alternative Polyadenylation of Mrna Precursors","volume":"18","author":"Tian","year":"2017","journal-title":"Nat Reviews Mol Cell Biology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/978-3-031-44087-8_17","article-title":"Posttranscriptional Regulation by Proteins and Noncoding Rnas","volume":"1441","author":"Aranega","year":"2024","journal-title":"Adv Exp Med Biol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1161\/CIRCRESAHA.115.307082","article-title":"Genome-Wide Polyadenylation Maps Reveal Dynamic Mrna 3'-End Formation in the Failing Human Heart","volume":"118","author":"Creemers","year":"2016","journal-title":"Circ Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nature13261","article-title":"CFIm25 Links Alternative Polyadenylation to Glioblastoma Tumour Suppression","volume":"510","author":"Masamha","year":"2014","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1038\/s41580-022-00507-5","article-title":"Context-Specific Regulation and Function of Mrna Alternative Polyadenylation","volume":"23","author":"Mitschka","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.bbrc.2022.01.093","article-title":"Cleavage Stimulating Factor 64 Depletion Mitigates Cardiac Fibrosis Through Alternative Polyadenylation","volume":"597","author":"Neupane","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1261\/rna.035899.112","article-title":"Alternative Polyadenylation: New Insights From Global Analyses","volume":"18","author":"Shi","year":"2012","journal-title":"Rna"},{"key":"B36","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.matbio.2022.06.001","article-title":"3'UTR Shortening of HAS2 Promotes Hyaluronan Hyper-Synthesis and Bioenergetic Dysfunction in Pulmonary Hypertension","volume":"111","author":"Tseng","year":"2022","journal-title":"Matrix Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/humu.20891","article-title":"Mechanistic Insights Into the Link Between a Polymorphism of the 3'UTR of the SLC7A1 Gene and Hypertension","volume":"30","author":"Yang","year":"2009","journal-title":"Hum Mutat"},{"key":"B38","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.gendis.2019.10.011","article-title":"Alternative Polyadenylation of Mrna and Its Role in Cancer","volume":"8","author":"Yuan","year":"2021","journal-title":"Genes Dis"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1172\/JCI122106","article-title":"Cleavage Factor 25 Deregulation Contributes to Pulmonary Fibrosis Through Alternative Polyadenylation","volume":"129","author":"Weng","year":"2019","journal-title":"J Clin Invest"},{"key":"B40","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1101\/gr.224451.117","article-title":"3' UTR Lengthening as a Novel Mechanism in Regulating Cellular Senescence","volume":"28","author":"Chen","year":"2018","journal-title":"Genome Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"14605","DOI":"10.1038\/ncomms14605","article-title":"The Role of Alternative Polyadenylation in the Antiviral Innate Immune Response","volume":"8","author":"Jia","year":"2017","journal-title":"Nat Commun"},{"key":"B42","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nature07509","article-title":"Alternative Isoform Regulation in Human Tissue Transcriptomes","volume":"456","author":"Wang","year":"2008","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1161\/CIRCULATIONAHA.119.039596","article-title":"Widespread Translational Control of Fibrosis in the Human Heart by RNA-binding Proteins","volume":"140","author":"Chothani","year":"2019","journal-title":"Circulation"},{"key":"B44","doi-asserted-by":"publisher","first-page":"110933","DOI":"10.1016\/j.jbc.2025.110933","article-title":"Noncoding Rnas Orchestrating the Central Dogma","volume":"302","author":"Lozano-Villada","year":"2026","journal-title":"J Biol Chem"},{"key":"B45","doi-asserted-by":"publisher","first-page":"869","DOI":"10.3390\/jcm13030869","article-title":"Approach to Decompensated Right Heart Failure in the Acute Setting","volume":"13","author":"Levitt","year":"2024","journal-title":"J Clinical Medicine"},{"key":"B46","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"100707","DOI":"10.1016\/j.crmeth.2024.100707","article-title":"PolyAMiner-Bulk Is a Deep Learning-Based Algorithm That Decodes Alternative Polyadenylation Dynamics From Bulk RNA-Seq Data","volume":"4","author":"Jonnakuti","year":"2024","journal-title":"Cell Rep Methods"},{"key":"B48","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1093\/nar\/gkaa398","article-title":"PolyA-miner: Accurate Assessment of Differential Alternative poly-adenylation from 3'Seq Data Using Vector Projections and Non-Negative Matrix Factorization","volume":"48","author":"Yalamanchili","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.phrs.2017.08.003","article-title":"Animal Models of Pulmonary Arterial Hypertension: A Systematic Review and meta-analysis of Data from 6126 Animals","volume":"125","author":"Sztuka","year":"2017","journal-title":"Pharmacol Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181384","article-title":"Downregulation of CFIm25 Amplifies Dermal Fibrosis Through Alternative Polyadenylation","volume":"217","author":"Weng","year":"2020","journal-title":"J Exp Med"},{"key":"B51","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1038\/msb.2011.69","article-title":"Transcriptional Activity Regulates Alternative Cleavage and Polyadenylation","volume":"7","author":"Ji","year":"2011","journal-title":"Mol Syst Biol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1111\/bph.15444","article-title":"Animal Models of Pulmonary Hypertension: Getting to the Heart of the Problem","volume":"179","author":"Dignam","year":"2022","journal-title":"Br J Pharmacol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"E1195","DOI":"10.1152\/ajpendo.90958.2008","article-title":"Biochemistry, Physiology, and Genetics of GPAT, AGPAT, and Lipin Enzymes in Triglyceride Synthesis","volume":"296","author":"Takeuchi","year":"2009","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1038\/s42003-023-05477-8","article-title":"Cholesterol Mediated Ferroptosis Suppression Reveals Essential Roles of Coenzyme Q and Squalene","volume":"6","author":"Sun","year":"2023","journal-title":"Commun Biol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"114983","DOI":"10.1016\/j.ecoenv.2023.114983","article-title":"Chlorpyrifos Induced Autophagy and Mitophagy in Common Carp Livers Through AMPK Pathway Activated by Energy Metabolism Disorder","volume":"258","author":"Cui","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1464815","DOI":"10.3389\/fcell.2024.1464815","article-title":"Mechanisms of the NAD(+) Salvage Pathway in Enhancing Skeletal Muscle Function","volume":"12","author":"Su","year":"2024","journal-title":"Front Cell Dev Biol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"3","DOI":"10.18632\/aging.100423","article-title":"Mitochondrial Oxidative Stress Caused by Sod2 Deficiency Promotes Cellular Senescence and Aging Phenotypes in the Skin","volume":"4","author":"Velarde","year":"2012","journal-title":"Aging (Albany NY)"},{"key":"B58","doi-asserted-by":"publisher","first-page":"101313","DOI":"10.1016\/j.arr.2021.101313","article-title":"Role of the DNAJ\/HSP40 Family in the Pathogenesis of Insulin Resistance and Type 2 Diabetes","volume":"67","author":"Diane","year":"2021","journal-title":"Ageing Res Rev"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e20230003","DOI":"10.14293\/genint.14.1.004","article-title":"Role of Mitogen-Activated Protein (MAP) Kinase Pathways in Metabolic Diseases","volume":"15","author":"Ng","year":"2024","journal-title":"Genome Integr"},{"key":"B60","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/jcb.25283","article-title":"Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of Stressed Cells","volume":"117","author":"Chen","year":"2016","journal-title":"J Cell Biochem"},{"key":"B61","doi-asserted-by":"publisher","first-page":"9765","DOI":"10.3390\/ijms22189765","article-title":"AMPK-mTOR Signaling and Cellular Adaptations in Hypoxia","volume":"22","author":"Chun","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026146","article-title":"Regulation of Cellular Metabolism and Hypoxia by p53","volume":"6","author":"Humpton","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B63","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1086\/678508","article-title":"The Sugen 5416\/hypoxia Mouse Model of Pulmonary Hypertension Revisited: Long-Term Follow-Up","volume":"4","author":"Vitali","year":"2014","journal-title":"Pulm Circ"},{"key":"B64","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.chembiol.2018.01.011","article-title":"N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H(2)S and Sulfane Sulfur Production","volume":"25","author":"Ezeri\u0146a","year":"2018","journal-title":"Cell Chem Biol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1161\/CIRCULATIONAHA.111.028571","article-title":"Squalene Synthase Inhibitor Lapaquistat Acetate: Could Anything Be Better than Statins?","volume":"123","author":"Liao","year":"2011","journal-title":"Circulation"}],"container-title":["British Journal of Biomedical Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontierspartnerships.org\/articles\/10.3389\/bjbs.2026.15687\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T06:10:28Z","timestamp":1771567828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontierspartnerships.org\/articles\/10.3389\/bjbs.2026.15687\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":65,"alternative-id":["10.3389\/bjbs.2026.15687"],"URL":"https:\/\/doi.org\/10.3389\/bjbs.2026.15687","relation":{},"ISSN":["2474-0896"],"issn-type":[{"value":"2474-0896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"article-number":"15687"}}