{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:00:12Z","timestamp":1791644412465,"version":"4.3.4"},"reference-count":68,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,11,12]]},"abstract":"<jats:p>On pathological stress, the heart reactivates several signaling pathways that traditionally were thought to be operational only in the developing heart. One of these pathways is the WNT signaling pathway. WNT controls heart development but is also modulated during adult heart remodeling. This review summarizes the currently available data regarding WNT signaling during left ventricular (LV) remodeling. Upstream, soluble frizzled-related proteins (sFRPs) block WNT-dependent activation of the canonical WNT pathway. By inhibition of WNT activation, these factors also reduce \u03b2-catenin\u2013dependent transcription by altering the ratio of cytoplasmic\/nuclear \u03b2-catenin. In experimental settings, sFRPs injected into the heart attenuated LV remodeling. sFRPs are secreted from autologous bone marrow\u2013derived mononuclear cells. Disheveled is a signaling intermediate of both the canonical and noncanonical WNT pathway. Similarly to the effect of sFRP, depletion of a disheveled isoform attenuated LV remodeling. In contrast, disheveled activation led to progressive dilated cardiomyopathy. Inhibition of nuclear \u03b2-catenin signaling downstream of the canonical WNT pathway significantly reduced postinfarct mortality and functional decline of LV function following chronic left anterior descending coronary artery ligation. WNT signaling also affects mobilization and homing of bone marrow\u2013derived vasculogenic progenitor cells. Finally, heart-specific WNT\/\u03b2-catenin interaction partners have been identified that will possibly allow targeting this pathway in a tissue-specific manner. In summary, the WNT pathway plays a pivotal role in adult cardiac remodeling and may be suitable for therapeutic interventions. Currently, several molecular and cellular mechanisms whereby WNT inhibition attenuates LV remodeling are proposed. Reactivation of the developmental program to restore functional LV myocardium from resident precursor cells may significantly contribute to this process.<\/jats:p>","DOI":"10.1161\/circresaha.110.223768","type":"journal-article","created":{"date-parts":[[2010,11,11]],"date-time":"2010-11-11T16:18:23Z","timestamp":1289492303000},"page":"1198-1208","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":193,"title":["WNT Signaling in Adult Cardiac Hypertrophy and Remodeling"],"prefix":"10.1161","volume":"107","author":[{"given":"Martin W.","family":"Bergmann","sequence":"first","affiliation":[{"name":"From the Experimental and Clinical Research Center, Charit\u00e9 Campus Buch &amp; Max Delbr\u00fcck Center for Molecular Medicine, Berlin, Germany. Present address: Department of Cardiology, ASKLEPIOS Klinik St Georg, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2006.11.012"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164680"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177350"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702859104"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605768103"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.109.141127"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000093186.22847.4C"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803437105"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.04.004"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.06.009"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1696"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40120"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07027"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000266605.63681.5a"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.148791"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.221531"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060063"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703113104"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.07.037"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700923104"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1906"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.05.018"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.642298"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1710"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.042"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23769"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.5.1730-1736.2001"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)54589-0"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.6.2427"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118992"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808393105"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1686208"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00376-4"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000039342.85015.5c"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610024104"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.11.016"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1811"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000171895.06914.2c"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.192138"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.05.006"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh0302.104466"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.02.093"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.02.013"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.6.17.4632"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2001.5174"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.219840"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27438"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.109.143297"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq067"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000255946.55091.24"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8551"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603808103"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3972007pe41"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000150366.08972.7f"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00576.2006"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02157-05"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.20.010403.113126"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.180463"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.172718"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.06.033"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000253139.82251.31"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2006.08.077"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1387"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-2-206"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.04.005"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701981104"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.05.005"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08191"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.110.223768","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:08:09Z","timestamp":1715558889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.110.223768"}},"subtitle":["Lessons Learned From Cardiac Development"],"editor":[{"given":"Michael","family":"K\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,11,12]]},"references-count":68,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2010,11,12]]}},"alternative-id":["10.1161\/CIRCRESAHA.110.223768"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.110.223768","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,12]]},"assertion":[{"value":"2010-11-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}