{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:45:51Z","timestamp":1787017551360,"version":"build-2736575974"},"reference-count":37,"publisher":"American Physiological Society","issue":"2","funder":[{"name":"Irving Institute\/Clinical Trials Office","award":["2017 pilot award"],"award-info":[{"award-number":["2017 pilot award"]}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 122805"],"award-info":[{"award-number":["R01 122805"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 131872"],"award-info":[{"award-number":["R01 131872"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005348","name":"American Association for Thoracic Surgery","doi-asserted-by":"publisher","award":["2016-2018"],"award-info":[{"award-number":["2016-2018"]}],"id":[{"id":"10.13039\/100005348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:p>\n                    Myostatin (MSTN) is a transforming growth factor (TGF)-\u03b2 superfamily member that acts as a negative regulator of muscle growth and may play a role in cardiac remodeling. We hypothesized that inhibition of activin type II receptors (ACTRII) to reduce MSTN signaling would reduce pathological cardiac remodeling in experimental heart failure (HF). C57BL\/6J mice underwent left anterior descending coronary artery ligation under anesthesia to induce myocardial infarction (MI) or no ligation (sham). MI and sham animals were each randomly divided into groups ( n \u2265 10 mice\/group) receiving an ACTRII or ACTRII\/TGF\u03b2 receptor-signaling inhibiting strategy: 1) myo-Fc group (weekly 10 mg\/kg Myo-Fc) or 2) Fol + TGFi group (daily 12 \u00b5g\/kg follistatin plus 2 mg\/kg TGF\u03b2 receptor inhibitor), versus controls. ACTRII\/TGFBR signaling inhibition preserved cardiac function by echocardiography and prevented an increase in brain natriuretic peptide (BNP). ACTRII\/TGFBR inhibition resulted in increased phosphorylation (P) of Akt and decreased P-p38 mitogen-activated protein kinase (MAPK) in MI mice. In vitro, Akt contributed to P-SMAD2,3, P-p38, and BNP regulation in cardiomyocytes. ACTRII\/TGFBR inhibition increased sarco\/endoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -ATPase (SERCA2a) levels and decreased unfolded protein response (UPR) markers in MI mice. ACTRII\/TGFBR inhibition was associated with a decrease in cardiac fibrosis and fibrosis markers, connective tissue growth factor (CTGF), type I collagen, fibronectin, \u03b1-smooth muscle actin, and matrix metalloproteinase (MMP)-12 in MI mice. MSTN exerted a direct regulation on the UPR marker eukaryotic translation initiation factor-2\u03b1 (eIf2\u03b1) in cardiomyocytes. Our study suggests that ACTRII ligand inhibition has beneficial effects on cardiac signaling and fibrosis after ischemic HF.\n                  <\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY Activin type II receptor ligand inhibition resulted in preserved cardiac function, a decrease in cardiac fibrosis, improved SERCA2a levels, and a prevention of the unfolded protein response in mice with myocardial infarction.<\/jats:p>","DOI":"10.1152\/ajpheart.00302.2019","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T10:28:27Z","timestamp":1577701707000},"page":"H378-H390","source":"Crossref","is-referenced-by-count":35,"title":["Activin type II receptor ligand signaling inhibition after experimental ischemic heart failure attenuates cardiac remodeling and prevents fibrosis"],"prefix":"10.1152","volume":"318","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2213-5809","authenticated-orcid":false,"given":"Estibaliz","family":"Castillero","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Akashi","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Najjar","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiping","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea Maria","family":"Brandstetter","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghai","family":"Liao","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Sperry","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Gailes","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Guaman","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Recht","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Schlosberg","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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