{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:57:21Z","timestamp":1793087841682,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>Cardiomyopathies are ascribed to a variety of etiologies, present with diverse clinical phenotypes, and lack disease\u2010modifying treatments. Mounting evidence implicates dysregulated activin receptor signaling in heart disease and highlights inhibition of this pathway as a potential therapeutic target. Here, we explored the effects of activin ligand inhibition using ActRIIB:ALK4\u2010Fc, a heterodimeric receptor fusion protein, in two mechanistically distinct murine models of cardiomyopathy. Treatment with ActRIIB:ALK4\u2010Fc significantly improved systolic or diastolic function in cardiomyopathy induced by neuromuscular disease or diabetes mellitus. Moreover, ActRIIB:ALK4\u2010Fc corrected Ca<jats:sup>2+<\/jats:sup> handling protein expression in diseased heart tissues, suggesting that activin signaling inhibition could alleviate cardiomyopathies in part by rebalancing aberrant intracellular Ca<jats:sup>2+<\/jats:sup> homeostasis\u2013a common underlying pathomechanism in diverse heart diseases.<\/jats:p>","DOI":"10.1002\/1873-3468.14464","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T08:58:45Z","timestamp":1659517125000},"page":"3145-3158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The activin receptor ligand trap <scp>ActRIIB<\/scp>:<scp>ALK4\u2010Fc<\/scp> ameliorates cardiomyopathy induced by neuromuscular disease and diabetes"],"prefix":"10.1002","volume":"596","author":[{"given":"Jia","family":"Li","sequence":"first","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Fredericks","sequence":"additional","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxin","family":"Tang","sequence":"additional","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marishka","family":"Cannell","sequence":"additional","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachindra","family":"Joshi","sequence":"additional","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra","family":"Kumar","sequence":"additional","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Andre","sequence":"additional","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2754-1782","authenticated-orcid":false,"given":"Rajasekhar N. V. S.","family":"Suragani","sequence":"additional","affiliation":[{"name":"Discovery Group Acceleron Pharma Inc., a subsidiary of Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1461"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100084\u20101"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311812"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000526"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010019\u20100284\u20100"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000011381"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2019.02.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314665"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000120704.97934.41"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.14744\/AnatolJCardiol.2017.7935"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ\u201018\u20100837"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq039"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010017\u20100634\u20101"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.008842"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.01.013"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau8680"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00302.2019"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI138634"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201097203\u20109"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22979"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201042209\u20107"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102199\u201011\u201022"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028569"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/db16\u20101237"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.02.081"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10840\u2010007\u20109168\u2010z"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v7.i7.410"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND\u2010180340"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00414"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000078"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/415198a"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2017.03.005"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004242"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20058823"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00107"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.647010"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9020520"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011040"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs425"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741\u2010012\u20109313\u20103"},{"key":"e_1_2_10_42_1","first-page":"82","article-title":"Mechanisms underlying diabetic cardiomyopathy: from pathophysiology to novel therapeutic targets","volume":"3","author":"Cong S","year":"2020","journal-title":"Cond Med"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01514"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.12.3201"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs218"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000672"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7090291"},{"key":"e_1_2_10_48_1","first-page":"103","article-title":"Heart repolarization changes after anthracycline therapy in the children with cancer","volume":"4","author":"Amoozgar H","year":"2014","journal-title":"Iran J Ped Hematol Oncol"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00441.2013"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.01.011"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.882068"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz5660"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00286.2018"}],"container-title":["FEBS Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.14464","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1873-3468.14464","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1873-3468.14464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T19:45:29Z","timestamp":1692560729000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1873-3468.14464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,29]]},"references-count":52,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/1873-3468.14464"],"URL":"https:\/\/doi.org\/10.1002\/1873-3468.14464","archive":["Portico"],"relation":{},"ISSN":["0014-5793","1873-3468"],"issn-type":[{"value":"0014-5793","type":"print"},{"value":"1873-3468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,29]]},"assertion":[{"value":"2022-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}