{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T20:24:48Z","timestamp":1763670288180,"version":"3.45.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, characterized by atrial fibrosis, a crucial substrate facilitating its initiation and persistence. CKAP4 (cytoskeleton-associated protein 4) has been associated with fibroblast activation; however, its involvement in atrial remodeling and AF susceptibility remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We measured serum CKAP4 by ELISA in 189 patients with drug-refractory AF and 79 controls and then correlated these levels with left atrial scar burden assessed by 3-dimensional electroanatomic mapping. CKAP4 cell-type specificity and AF-associated regulation were evaluated in human single-cell\/single-nucleus RNA-seq data sets (GSE238242 and GSE224959). CKAP4 regulation and function were examined in mice subjected to transverse aortic constriction or Ang II (angiotensin II) infusion and in neonatal rat atrial fibroblasts stimulated with Ang II using CKAP4 knockdown\/overexpression. AF inducibility was tested by transesophageal burst pacing. Mechanistic studies assessed CKAP4 interactions with wingless\/INT signaling pathway (WNT) 3A\/WNT5A (co-immunoprecipitation and proximity ligation) and perturbed \u03b2-catenin signaling with an agonist (Wnt\/\u03b2-catenin pathway agonist) or inhibitor (\u03b2-catenin\/TCF pathway inhibitor) in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Serum CKAP4 was higher in AF than controls (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and correlated with regional and total scar burden (r=0.16\u20130.29; all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05). CKAP4 was enriched in fibroblasts and upregulated in AF in both human data sets. Transverse aortic constriction and Ang II increased atrial CKAP4 in vivo. In atrial fibroblasts, CKAP4 knockdown reduced \u03b1-Smooth Muscle Actin (\u03b1-SMA), collagen I\/III, vimentin, and migration, whereas overexpression produced opposite effects. In mice, CKAP4 knockdown attenuated left atrial fibrosis and reduced AF inducibility. CKAP4 interacted with WNT3A and WNT5A and activated \u03b2-catenin signaling; SKL2001 rescued the antifibrotic\/antiarrhythmic effects of CKAP4 knockdown, while \u03b2-catenin\/TCF pathway inhibitor blunted CKAP4-overexpression\u2013induced collagen synthesis and migration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>CKAP4 promotes atrial fibrosis and increases AF vulnerability through the WNT\/\u03b2-catenin signaling pathway, highlighting the CKAP4\u2013WNT\/\u03b2-catenin axis as a promising therapeutic target to attenuate atrial structural remodeling in AF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circep.125.014217","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:17:31Z","timestamp":1761729451000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["CKAP4 Promotes Atrial Fibrosis and Enhances Atrial Fibrillation Vulnerability via WNT\/\u03b2-Catenin Activation"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8224-7063","authenticated-orcid":true,"given":"Yuntao","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Cardiology, Tongji Hospital (Y.F., Z.C., Y.G., X.L., H.T.), Tongji University School of Medicine, Shanhgai, China."},{"name":"Department of Thoracic Surgery, Shanghai Pulmonary Hospital (Y.F.), Tongji University School of Medicine, Shanhgai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhisong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tongji Hospital (Y.F., Z.C., Y.G., X.L., H.T.), Tongji University School of Medicine, Shanhgai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tongji Hospital (Y.F., Z.C., Y.G., X.L., H.T.), Tongji University School of Medicine, Shanhgai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tongji Hospital (Y.F., Z.C., Y.G., X.L., H.T.), Tongji University School of Medicine, Shanhgai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6542-7927","authenticated-orcid":true,"given":"Hongwei","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tongji Hospital (Y.F., Z.C., Y.G., X.L., H.T.), Tongji University School of Medicine, Shanhgai, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316340"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2020-317915"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz786"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad396"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2890-8"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.11909\/j.issn.1671-5411.2017.04.008"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab170"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.552056"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-22-571"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030742"},{"key":"e_1_3_3_12_2","first-page":"2270","article-title":"CKAP4 participates in tryptase-induced phenotypic conversion in atrial fibroblasts through PAR2\/p38\/JNK pathway.","volume":"13","author":"Tan H","year":"2021","unstructured":"Tan H, Chen Z, Chen F, Xu W, Liu X. 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