{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:07:07Z","timestamp":1785434827125,"version":"3.56.0"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>The aim was to determine the renoprotective effects of serelaxin in the setting of chronic heart failure.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What are the main findings and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Our data indicate that serelaxin can reduce renal fibrosis and inflammation in experimental heart failure. Currently, there are no effective treatments to rescue renal function in heart failure patients, and our data suggest that serelaxin might have the potential to reduce renal fibrosis and inflammation in heart failure.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Serelaxin has been demonstrated to attenuate renal fibrosis and inflammation in cardiorenal disease. In the present study, we tested the hypothesis that serelaxin can prevent the decline in renal function in dilated cardiomyopathy (DCM) by targeting renal fibrosis and inflammation. Male transgenic mice with DCM (<jats:italic>n\u00a0<\/jats:italic>=\u00a016) and their wild\u2010type littermates (WT; <jats:italic>n\u00a0<\/jats:italic>=\u00a020) were administered either vehicle or serelaxin (500\u00a0\u03bcg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0day<jats:sup>\u22121<\/jats:sup>; subcutaneous minipumps; 8\u00a0weeks). Cardiac function was assessed via echocardiography before and during the eighth week of serelaxin treatment. Renal function and inflammation as well as cardiac and renal fibrosis were assessed at the end of the study. Serelaxin had minimal effect on cardiac function (<jats:italic>P<\/jats:italic>\u00a0\u2265\u00a00.99). Tubulointerstitial and glomerular fibrosis were \u223c3\u2010fold greater in vehicle\u2010treated DCM mice compared with vehicle\u2010treated WT mice (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.001). Renal mRNA expression of <jats:italic>Tnf\u03b1<\/jats:italic> and <jats:italic>Il1\u03b1<\/jats:italic> were \u223c4\u2010 and \u223c3\u2010fold greater, respectively, in vehicle\u2010treated DCM mice compared with vehicle\u2010treated WT mice (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05). Tubulointerstitial and glomerular fibrosis were 46 and 45% less, respectively, in serelaxin\u2010treated DCM mice than in vehicle\u2010treated DCM mice (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.01). Renal cortical mRNA expression of <jats:italic>Tnf\u03b1<\/jats:italic> and <jats:italic>Il1\u03b1<\/jats:italic> were 56 and 58% less, respectively, in the former group compared with the latter (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.05). The urinary albumin:creatinine ratio was \u223c3\u2010fold greater in vehicle\u2010treated DCM mice compared with vehicle\u2010treated WT mice (<jats:italic>P\u00a0<\/jats:italic>=\u00a00.02). The urinary albumin:creatinine ratio was not significantly different between vehicle\u2010treated DCM mice and serelaxin\u2010treated DCM mice (<jats:italic>P\u00a0<\/jats:italic>=\u00a00.38). These data suggest that serelaxin can attenuate renal fibrosis and inflammation and has the potential to exert renoprotective effects in DCM.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep087189","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T09:16:17Z","timestamp":1539335777000},"page":"1593-1602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Serelaxin attenuates renal inflammation and fibrosis in a mouse model of dilated cardiomyopathy"],"prefix":"10.1113","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-3103","authenticated-orcid":false,"given":"Beverly","family":"Giam","sequence":"first","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"},{"name":"Central Clinical School Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Yin","family":"Chu","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjaya","family":"Kuruppu","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute Department of Biochemistry &amp; Molecular Biology Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Ian","family":"Smith","sequence":"additional","affiliation":[{"name":"Biomedicine Discovery Institute Department of Biochemistry &amp; Molecular Biology Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Horlock","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Murali","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Kiriazis","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Jun","family":"Du","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"},{"name":"Department of Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niwanthi W.","family":"Rajapakse","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"},{"name":"School of Biomedical Sciences University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.10103"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.110.960831"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-011-9261-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000349968"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs149"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.1.71"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.059003876.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12757"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17927-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047160"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270818"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12130"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000051660.82593.19"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000171930.00697.2f"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2013-0307"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-016-0979-8"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2005.03.030"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00083.2015"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00145.2010"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39604"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.05.011"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00407.2014"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-346007"},{"key":"e_1_2_7_25_1","first-page":"920195","article-title":"The cardiorenal syndrome: A review","volume":"2011","author":"Shah B. 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