{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:13:09Z","timestamp":1772165589941,"version":"3.50.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cardiovasc Disord"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that\n                      <jats:italic>catalase<\/jats:italic>\n                      (\n                      <jats:italic>CAT<\/jats:italic>\n                      ) is one of the potential targets of bFGF-induced APA regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the\n                      <jats:italic>CAT<\/jats:italic>\n                      gene may contribute to bFGF-induced calcium deposition inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12872-024-03775-5","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T09:02:09Z","timestamp":1709110929000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene"],"prefix":"10.1186","volume":"24","author":[{"given":"Jiajun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingli","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangfeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"issue":"7","key":"3775_CR1","doi-asserted-by":"publisher","first-page":"e39980","DOI":"10.1371\/journal.pone.0039980","volume":"7","author":"CM McCoy","year":"2012","unstructured":"McCoy CM, Nicholas DQ, Masters KS. Sex-related differences in gene expression by porcine aortic valvular interstitial cells. PLoS One. 2012;7(7):e39980.","journal-title":"PLoS One"},{"issue":"2","key":"3775_CR2","doi-asserted-by":"publisher","first-page":"108","DOI":"10.15420\/ecr.2015.10.2.108","volume":"10","author":"DA Lerman","year":"2015","unstructured":"Lerman DA, Prasad S, Alotti N. Calcific aortic valve disease: molecular mechanisms and therapeutic approaches. Eur Cardiol. 2015;10(2):108\u201312.","journal-title":"Eur Cardiol"},{"issue":"3","key":"3775_CR3","doi-asserted-by":"publisher","first-page":"e005041","DOI":"10.1161\/JAHA.116.005041","volume":"6","author":"AM Porras","year":"2017","unstructured":"Porras AM, van Engeland NC, Marchbanks E, McCormack A, Bouten CV, Yacoub MH, Latif N, Masters KS. Robust generation of quiescent porcine Valvular interstitial cell cultures. J Am Heart Assoc. 2017;6(3):e005041.","journal-title":"J Am Heart Assoc"},{"issue":"4","key":"3775_CR4","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1161\/CIRCULATIONAHA.117.032291","volume":"138","author":"F Schlotter","year":"2018","unstructured":"Schlotter F, Halu A, Goto S, Blaser MC, Body SC, Lee LH, Higashi H, DeLaughter DM, Hutcheson JD, Vyas P, et al. Spatiotemporal multi-omics mapping generates a molecular atlas of the aortic valve and reveals networks driving disease. Circulation. 2018;138(4):377\u201393.","journal-title":"Circulation"},{"issue":"12","key":"3775_CR5","doi-asserted-by":"publisher","first-page":"2910","DOI":"10.1161\/ATVBAHA.120.314789","volume":"40","author":"K Xu","year":"2020","unstructured":"Xu K, Xie S, Huang Y, Zhou T, Liu M, Zhu P, Wang C, Shi J, Li F, Sellke FW, et al. Cell-type transcriptome atlas of human aortic valves reveal cell heterogeneity and endothelial to mesenchymal transition involved in calcific aortic valve disease. Arterioscler Thromb Vasc Biol. 2020;40(12):2910\u201321.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"3775_CR6","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s40364-020-00249-6","volume":"8","author":"F Ren","year":"2020","unstructured":"Ren F, Zhang N, Zhang L, Miller E, Pu JJ. Alternative polyadenylation: a new frontier in post transcriptional regulation. Biomark Res. 2020;8(1):67.","journal-title":"Biomark Res"},{"issue":"1","key":"3775_CR7","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nrm.2016.116","volume":"18","author":"B Tian","year":"2017","unstructured":"Tian B, Manley JL. Alternative polyadenylation of mRNA precursors. Nat Rev Mol Cell Biol. 2017;18(1):18\u201330.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"3775_CR8","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1089\/cell.2012.0077","volume":"15","author":"F Hu","year":"2013","unstructured":"Hu F, Wang X, Liang G, Lv L, Zhu Y, Sun B, Xiao Z. Effects of epidermal growth factor and basic fibroblast growth factor on the proliferation and osteogenic and neural differentiation of adipose-derived stem cells. Cell Reprogram. 2013;15(3):224\u201332.","journal-title":"Cell Reprogram"},{"issue":"7","key":"3775_CR9","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1634\/stemcells.2005-0191","volume":"24","author":"A Schmidt","year":"2006","unstructured":"Schmidt A, Ladage D, Schink\u00f6the T, Klausmann U, Ulrichs C, Klinz FJ, Brixius K, Arnhold S, Desai B, Mehlhorn U, et al. Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells. 2006;24(7):1750\u20138.","journal-title":"Stem Cells"},{"issue":"24","key":"3775_CR10","first-page":"6910","volume":"24","author":"HB Akman","year":"2015","unstructured":"Akman HB, Oyken M, Tuncer T, Can T, Erson-Bensan AE. 3'UTR shortening and EGF signaling: implications for breast cancer. Hum Mol Genet. 2015;24(24):6910\u201320.","journal-title":"Hum Mol Genet"},{"issue":"10","key":"3775_CR11","doi-asserted-by":"publisher","first-page":"5903","DOI":"10.1016\/S0021-9258(19)39448-7","volume":"265","author":"Y Kato","year":"1990","unstructured":"Kato Y, Iwamoto M. Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation. J Biol Chem. 1990;265(10):5903\u20139.","journal-title":"J Biol Chem"},{"key":"3775_CR12","doi-asserted-by":"publisher","first-page":"7671638","DOI":"10.1155\/2019\/7671638","volume":"2019","author":"Y Huang","year":"2019","unstructured":"Huang Y, Xu K, Zhou T, Zhu P, Dong N, Shi J. Comparison of rapidly proliferating, multipotent aortic valve-derived stromal cells and valve interstitial cells in the human aortic valve. Stem Cells Int. 2019;2019:7671638.","journal-title":"Stem Cells Int"},{"key":"3775_CR13","doi-asserted-by":"publisher","first-page":"109985","DOI":"10.1016\/j.biopha.2020.109985","volume":"125","author":"Y Huang","year":"2020","unstructured":"Huang Y, Zhou X, Liu M, Zhou T, Shi J, Dong N, Xu K. The natural compound andrographolide inhibits human aortic valve interstitial cell calcification via the NF-kappa B\/Akt\/ERK pathway. Biomed Pharmacother. 2020;125:109985.","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"3775_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms6274","volume":"5","author":"Z Xia","year":"2014","unstructured":"Xia Z, Donehower LA, Cooper TA, Neilson JR, Wheeler DA, Wagner EJ, Li W. Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3\u2032-UTR landscape across seven tumour types. Nat Commun. 2014;5(1):1\u201313.","journal-title":"Nat Commun"},{"issue":"1","key":"3775_CR15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-016-0001-8","volume":"6","author":"X Lin","year":"2016","unstructured":"Lin X, Zhao L, Tang S, Zhou Q, Lin Q, Li X, Zheng H, Gao H. Metabolic effects of basic fibroblast growth factor in streptozotocin-induced diabetic rats: a 1 H NMR-based metabolomics investigation. Sci Rep. 2016;6(1):1\u20139.","journal-title":"Sci Rep"},{"issue":"2","key":"3775_CR16","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1006\/dbio.1995.1229","volume":"170","author":"H Shiba","year":"1995","unstructured":"Shiba H, Nakamura S, Shirakawa M, Nakanishi K, Okamoto H, Satakeda H, Noshiro M, Kamihagi K, Katayama M, Kato Y. Effects of basic fibroblast growth factor on proliferation, the expression of osteonectin (SPARC) and alkaline phosphatase, and calcification in cultures of human pulp cells. Dev Biol. 1995;170(2):457\u201366.","journal-title":"Dev Biol"},{"issue":"1","key":"3775_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13058-015-0590-3","volume":"17","author":"S Li","year":"2015","unstructured":"Li S, Payne S, Wang F, Claus P, Su Z, Groth J, Geradts J, de Ridder G, Alvarez R, Marcom PK. Nuclear basic fibroblast growth factor regulates triple-negative breast cancer chemo-resistance. Breast Cancer Res. 2015;17(1):1\u201316.","journal-title":"Breast Cancer Res"},{"issue":"4","key":"3775_CR18","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1023\/A:1016080321956","volume":"4","author":"Y-J Jih","year":"2001","unstructured":"Jih Y-J, Lien W-H, Tsai W-C, Yang G-W, Li C, Wu L-W. Distinct regulation of genes by bFGF and VEGF-A in endothelial cells. Angiogenesis. 2001;4(4):313\u201321.","journal-title":"Angiogenesis"},{"key":"3775_CR19","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1471-2350-11-6","volume":"11","author":"AZ Fan","year":"2010","unstructured":"Fan AZ, Yesupriya A, Chang MH, House M, Fang J, Ned R, Hayes D, Dowling NF, Mokdad AH. Gene polymorphisms in association with emerging cardiovascular risk markers in adult women. BMC Med Genet. 2010;11:6.","journal-title":"BMC Med Genet"},{"issue":"4","key":"3775_CR20","doi-asserted-by":"publisher","first-page":"e1005166","DOI":"10.1371\/journal.pgen.1005166","volume":"11","author":"W Li","year":"2015","unstructured":"Li W, You B, Hoque M, Zheng D, Luo W, Ji Z, Park JY, Gunderson SI, Kalsotra A, Manley JL, et al. Systematic profiling of poly(a)+ transcripts modulated by core 3\u2032 end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation. PLoS Genet. 2015;11(4):e1005166.","journal-title":"PLoS Genet"},{"issue":"3","key":"3775_CR21","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.tcb.2015.10.012","volume":"26","author":"C Mayr","year":"2016","unstructured":"Mayr C. Evolution and biological roles of alternative 3'UTRs. Trends Cell Biol. 2016;26(3):227\u201337.","journal-title":"Trends Cell Biol"},{"issue":"2","key":"3775_CR22","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s00018-003-3206-5","volume":"61","author":"P Chelikani","year":"2004","unstructured":"Chelikani P, Fita I, Loewen PC. Diversity of structures and properties among catalases. Cell Mol Life Sci. 2004;61(2):192\u2013208.","journal-title":"Cell Mol Life Sci"},{"issue":"1","key":"3775_CR23","doi-asserted-by":"publisher","first-page":"13","DOI":"10.4321\/S1889-836X2017000100003","volume":"9","author":"L Mart\u00ednez Arias","year":"2017","unstructured":"Mart\u00ednez Arias L, Panizo Garc\u00eda S, Carrillo L\u00f3pez N, Barrio V\u00e1zquez S, Quir\u00f3s Gonz\u00e1lez I, Rom\u00e1n Garc\u00eda P, Mora Valenciano I, Miguel Fern\u00e1ndez D, A\u00f1\u00f3n \u00c1lvarez E, Fern\u00e1ndez Mart\u00edn JL, et al. Efecto de la enzima antioxidante catalasa en la calcificaci\u00f3n vascular y desmineralizaci\u00f3n \u00f3sea. Rev Osteoporos Metab Miner. 2017;9(1):13\u20139.","journal-title":"Rev Osteoporos Metab Miner"},{"issue":"2","key":"3775_CR24","doi-asserted-by":"publisher","first-page":"e66","DOI":"10.1161\/ATVBAHA.112.300177","volume":"33","author":"E Branchetti","year":"2013","unstructured":"Branchetti E, Sainger R, Poggio P, Grau JB, Patterson-Fortin J, Bavaria JE, Chorny M, Lai E, Gorman RC, Levy RJ, et al. Antioxidant enzymes reduce DNA damage and early activation of valvular interstitial cells in aortic valve sclerosis. Arterioscler Thromb Vasc Biol. 2013;33(2):e66\u201374.","journal-title":"Arterioscler Thromb Vasc Biol"}],"container-title":["BMC Cardiovascular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-024-03775-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12872-024-03775-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12872-024-03775-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T09:03:44Z","timestamp":1709111024000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccardiovascdisord.biomedcentral.com\/articles\/10.1186\/s12872-024-03775-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,28]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3775"],"URL":"https:\/\/doi.org\/10.1186\/s12872-024-03775-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2674975\/v1","asserted-by":"object"}]},"ISSN":["1471-2261"],"issn-type":[{"value":"1471-2261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,28]]},"assertion":[{"value":"9 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the local ethics committee of Changhai Hospital, Second Military Medical University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"128"}}