{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T21:21:33Z","timestamp":1768080093940,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL115036"],"award-info":[{"award-number":["HL115036"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS089707"],"award-info":[{"award-number":["NS089707"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Humans with dilated cardiomyopathy (DCM) and heart failure (HF) develop low levels of corin, a multi-domain, cardiac-selective serine protease involved in natriuretic peptide cleavage and sodium and water regulation. However, experimental restoration of corin levels markedly attenuates HF progression. To determine whether the beneficial effects of corin in HF require catalytic activity, we engineered cardiac overexpression of an enzymatically inactive corin transgene (corin-Tg(i)). On a wild-type (WT) background, corin-Tg(i) had no evident phenotypic effects. However, in a well-established genetic model of DCM, corin-Tg(i)\/DCM mice had increased survival (p &lt; 0.01 to 0.001) vs. littermate corin-WT\/DCM controls. Pleural effusion (p &lt; 0.01), lung edema (p &lt; 0.05), systemic extracellular free water (p &lt; 0.01), and heart weight were decreased (p &lt; 0.01) in corin-Tg(i)\/DCM vs. corin-WT\/DCM mice. Cardiac ejection fraction and fractional shortening improved (p &lt; 0.01), while ventricular dilation decreased (p &lt; 0.0001) in corin-Tg(i)\/DCM mice. Plasma atrial natriuretic peptide, cyclic guanosine monophosphate, and neprilysin were significantly decreased. Cardiac phosphorylated glycogen synthase kinase-3\u03b2 (pSer9-GSK3\u03b2) levels were increased in corin(i)-Tg\/DCM mice (p &lt; 0.01). In summary, catalytically inactive corin-Tg(i) decreased fluid retention, improved contractile function, decreased HF biomarkers, and diminished cardiac GSK3\u03b2 activity. Thus, the protective effects of cardiac corin on HF progression and survival in experimental DCM do not require the serine protease activity of the molecule.<\/jats:p>","DOI":"10.3390\/ijms21010203","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T11:42:47Z","timestamp":1577446967000},"page":"203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cardiac-Specific Overexpression of Catalytically Inactive Corin Reduces Edema, Contractile Dysfunction, and Death in Mice with Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"21","author":[{"given":"Ranjana","family":"Tripathi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2014Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-2210","authenticated-orcid":false,"given":"Ryan D.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2014Phoenix, Phoenix, AZ 85004, USA"},{"name":"Departments of Comparative Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tai-Hwang M.","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiilyan K.","family":"Houng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radhika M.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2014Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy L.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2014Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-9029","authenticated-orcid":false,"given":"Inna P.","family":"Gladysheva","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Arizona College of Medicine\u2014Phoenix, Phoenix, AZ 85004, USA"},{"name":"Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart Disease and Stroke Statistics-2019 Update: A Report from the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2174\/1573403X09666131117164352","article-title":"Stage B: What is the evidence for treatment of asymptomatic left ventricular dysfunction?","volume":"11","author":"Reed","year":"2015","journal-title":"Curr. 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