Human Relaxin‐2 Fusion Protein Treatment Prevents and Reverses Isoproterenol‐Induced Hypertrophy and Fibrosis in Mouse Heart

• DOI: 10.1161/jaha.119.013465
• Publication Date: 2019-12-10T10:00:37Z
• Authors: Junhui Sun; Weidong Hao; Natasha Fillmore; Hanley Ma; Danielle Springer; Zu‐Xi Yu; Agnieszka Sadowska; Andrew Garcia; Ruoyan Chen; Vanessa Muniz‐Medina; Kim Rosenthal; Jia Lin; Denison Kuruvilla; Jane Osbourn; Sotirios K. Karat...; Jill Walker; Elizabeth Murphy
• Keywords: Relaxin; Myocardial hypertrophy; Myocardial fibrosis

Background Heart failure is one of the leading causes death in Western countries, and there a need for new therapeutic approaches. Relaxin‐2 peptide hormone that mediates pleiotropic cardiovascular effects, including antifibrotic, angiogenic, vasodilatory, antiapoptotic, anti‐inflammatory effects vitro vivo. Methods Results We developed RELAX 10, fusion protein composed human relaxin‐2 Fc antibody, to test hypothesis extended exposure could reduce cardiac hypertrophy fibrosis. 10 demonstrated same specificity similar activity as peptide. The terminal half‐life was 7 days mouse 3.75 rat after subcutaneous administration. evaluated whether treatment with prevent reverse isoproterenol‐induced fibrosis mice. Isoproterenol administration mice resulted increased compared vehicle. Coadministration significantly attenuated untreated animals. transforming growth factor β1 (TGF‐β1)–induced fibrotic signaling, which by 10. found also kinase B/endothelial NO synthase signaling S‐nitrosylation. In reversal study, 10‐treated animals showed reduced collagen levels. Conclusions These findings support potential role heart failure.