{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:52:34Z","timestamp":1792702354412,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ftirma Kurumu","doi-asserted-by":"publisher","award":["SBAG-4130"],"award-info":[{"award-number":["SBAG-4130"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ftirma Kurumu","doi-asserted-by":"publisher","award":["108S375"],"award-info":[{"award-number":["108S375"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2021,10,15]]},"abstract":"<jats:p>Objectives. Transcriptomics of atrial fibrillation (AFib) in the setting of chronic primary mitral regurgitation (MR) remains to be characterized. We aimed to compare the gene expression profiles of patients with degenerative MR in AFib and sinus rhythm (SR) for a clearer picture of AFib pathophysiology. Methods. After transcriptomic analysis and bioinformatics (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>n<\/a:mi>\n                        <a:mo>=<\/a:mo>\n                        <a:mn>59<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>), differentially expressed genes were defined using 1.5-fold change as the threshold. Additionally, independent datasets from GEO were included as meta-analyses. Results. QRT-PCR analysis confirmed that AFib persistence was associated with increased expression molecular changes underlying a transition to heart failure (NPPB, <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>P<\/c:mi>\n                        <c:mo>=<\/c:mo>\n                        <c:mn>0.002<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>; ANGPTL2, <jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>P<\/e:mi>\n                        <e:mo>=<\/e:mo>\n                        <e:mn>0.002<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>; IGFBP2, <jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>P<\/g:mi>\n                        <g:mo>=<\/g:mo>\n                        <g:mn>0.010<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>), structural remodeling including changes in the extracellular matrix and cellular stress response (COLQ, <jats:inline-formula>\n                     <i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                        <i:mi>P<\/i:mi>\n                        <i:mo>=<\/i:mo>\n                        <i:mn>0.003<\/i:mn>\n                     <\/i:math>\n                  <\/jats:inline-formula>; COMP, <jats:inline-formula>\n                     <k:math xmlns:k=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                        <k:mi>P<\/k:mi>\n                        <k:mo>=<\/k:mo>\n                        <k:mn>0.028<\/k:mn>\n                     <\/k:math>\n                  <\/jats:inline-formula>; DHRS9, <jats:inline-formula>\n                     <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                        <m:mi>P<\/m:mi>\n                        <m:mo>=<\/m:mo>\n                        <m:mn>0.038<\/m:mn>\n                     <\/m:math>\n                  <\/jats:inline-formula>; CHGB, <jats:inline-formula>\n                     <o:math xmlns:o=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\">\n                        <o:mi>P<\/o:mi>\n                        <o:mo>=<\/o:mo>\n                        <o:mn>0.038<\/o:mn>\n                     <\/o:math>\n                  <\/jats:inline-formula>), and cellular stress response (DNAJA4, <jats:inline-formula>\n                     <q:math xmlns:q=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M9\">\n                        <q:mi>P<\/q:mi>\n                        <q:mo>=<\/q:mo>\n                        <q:mn>0.038<\/q:mn>\n                     <\/q:math>\n                  <\/jats:inline-formula>). Furthermore, AFib persistence was associated with decreased expression of the targets of structural remodeling (BMP7, <jats:inline-formula>\n                     <s:math xmlns:s=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M10\">\n                        <s:mi>P<\/s:mi>\n                        <s:mo>=<\/s:mo>\n                        <s:mn>0.021<\/s:mn>\n                     <\/s:math>\n                  <\/jats:inline-formula>) and electrical remodeling (CACNB2, <jats:inline-formula>\n                     <u:math xmlns:u=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M11\">\n                        <u:mi>P<\/u:mi>\n                        <u:mo>=<\/u:mo>\n                        <u:mn>0.035<\/u:mn>\n                     <\/u:math>\n                  <\/jats:inline-formula>; MCOLN3, <jats:inline-formula>\n                     <w:math xmlns:w=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M12\">\n                        <w:mi>P<\/w:mi>\n                        <w:mo>=<\/w:mo>\n                        <w:mn>0.035<\/w:mn>\n                     <\/w:math>\n                  <\/jats:inline-formula>) in both left and right atrial samples. The transmission electron microscopic analysis confirmed ultrastructural atrial remodeling and autophagy in human AFib atrial samples. Conclusions. Atrial cardiomyocyte remodeling in persistent AFib is closely linked to alterations in gene expression profiles compared to SR in patients with primary MR. Study findings may lead to novel therapeutic targets. This trial is registered with ClinicalTrials.gov identifier: NCT00970034.<\/jats:p>","DOI":"10.1155\/2021\/5516185","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T18:06:58Z","timestamp":1634321218000},"page":"1-12","source":"Crossref","is-referenced-by-count":29,"title":["Molecular Signatures of Human Chronic Atrial Fibrillation in Primary Mitral Regurgitation"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2407-2450","authenticated-orcid":true,"given":"G\u00fcnseli","family":"\u00c7ubuk\u00e7uo\u011flu Deniz","sequence":"first","affiliation":[{"name":"Stem Cell Institute, Ankara University, Ankara, Turkey"},{"name":"Biotechnology Institute, Ankara University, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0578-1657","authenticated-orcid":true,"given":"Serkan","family":"Durdu","sequence":"additional","affiliation":[{"name":"Biotechnology Institute, Ankara University, Ankara, Turkey"},{"name":"Department of Cardiovascular Surgery, Heart Center, Ankara University School of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-6133","authenticated-orcid":true,"given":"Ye\u015fim","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Biotechnology Institute, Ankara University, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-269X","authenticated-orcid":true,"given":"Esra","family":"Erdemli","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Ankara University School of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7940-2499","authenticated-orcid":true,"given":"Hilal","family":"\u00d6zda\u011f","sequence":"additional","affiliation":[{"name":"Biotechnology Institute, Ankara University, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5191-5505","authenticated-orcid":true,"given":"Ahmet Ruchan","family":"Akar","sequence":"additional","affiliation":[{"name":"Stem Cell Institute, Ankara University, Ankara, Turkey"},{"name":"Biotechnology Institute, Ankara University, Ankara, Turkey"},{"name":"Department of Cardiovascular Surgery, Heart Center, Ankara University School of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61774-8"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.005119"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.107.754564"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0133-9"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.02.555"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140047"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3682"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.114.001632"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2005.09.004"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2017.03.002"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026389"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.07.103"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000165480.82737.33"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2012.11.013"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxw030"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt439"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-011-1281-5"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5776"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2010.01718.x"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.15171\/jcvtr.2014.007"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1111\/pace.12788"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.008108"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.08.012"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbacli.2017.02.002"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079792"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp251"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.169185"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2011.07.056"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.006458"},{"key":"31","volume-title":"Netter\u2019s Essential Histology","author":"O. 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