{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:12:34Z","timestamp":1790172754252,"version":"4.1.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,12,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Heart failure is one of the leading causes of death in Western countries, and there is a need for new therapeutic approaches. Relaxin\u20102 is a peptide hormone that mediates pleiotropic cardiovascular effects, including antifibrotic, angiogenic, vasodilatory, antiapoptotic, and anti\u2010inflammatory effects in\u00a0vitro and in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We developed\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10, a fusion protein composed of human relaxin\u20102 hormone and the Fc of a human antibody, to test the hypothesis that extended exposure of the relaxin\u20102 peptide could reduce cardiac hypertrophy and fibrosis.\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10 demonstrated the same specificity and similar in\u00a0vitro activity as the relaxin\u20102 peptide. The terminal half\u2010life of\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10 was 7\u00a0days in mouse and 3.75\u00a0days in rat after subcutaneous administration. We evaluated whether treatment with\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10 could prevent and reverse isoproterenol\u2010induced cardiac hypertrophy and fibrosis in mice. Isoproterenol administration in mice resulted in increased cardiac hypertrophy and fibrosis compared with vehicle. Coadministration with\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10 significantly attenuated the cardiac hypertrophy and fibrosis compared with untreated animals. Isoproterenol administration significantly increased transforming growth factor \u03b21 (TGF\u2010\u03b21)\u2013induced fibrotic signaling, which was attenuated by\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10. We found that\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10 also significantly increased protein kinase B\/endothelial NO synthase signaling and protein S\u2010nitrosylation. In the reversal study,\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10\u2010treated animals showed significantly reduced cardiac hypertrophy and collagen levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      These findings support a potential role for\n                      <jats:styled-content style=\"fixed-case\">RELAX<\/jats:styled-content>\n                      10 in the treatment of heart failure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.119.013465","type":"journal-article","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T05:00:37Z","timestamp":1575954037000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Human Relaxin\u20102 Fusion Protein Treatment Prevents and Reverses Isoproterenol\u2010Induced Hypertrophy and Fibrosis in Mouse Heart"],"prefix":"10.1161","volume":"8","author":[{"given":"Junhui","family":"Sun","sequence":"first","affiliation":[{"name":"Cardiac Physiology Section\/Cardiovascular Branch National Heart, Lung, and Blood Institute\/National Institutes of Health Bethesda MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Hao","sequence":"additional","affiliation":[{"name":"AstraZeneca Gaithersburg MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Fillmore","sequence":"additional","affiliation":[{"name":"Cardiac 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