| First Author | Maruyama S | Year | 2018 |
| Journal | J Am Heart Assoc | Volume | 7 |
| Issue | 12 | PubMed ID | 29887522 |
| Mgi Jnum | J:325297 | Mgi Id | MGI:6859958 |
| Doi | 10.1161/JAHA.117.008441 | Citation | Maruyama S, et al. (2018) Relaxin Family Member Insulin-Like Peptide 6 Ameliorates Cardiac Fibrosis and Prevents Cardiac Remodeling in Murine Heart Failure Models. J Am Heart Assoc 7(12) |
| abstractText | BACKGROUND: The insulin/insulin-like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin-2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin-like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss-of-function and protein delivery methods. METHODS AND RESULTS: Insl6-deficient and wild-type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks. In both models, Insl6-knockout mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation. Cardiac dysfunction in the Insl6-knockout mice was associated with more extensive cardiac fibrosis and greater expression of fibrosis-associated genes. The continuous infusion of chemically synthesized INSL6 significantly attenuated left ventricular systolic dysfunction and cardiac fibrosis induced by isoproterenol infusion. Gene expression profiling suggests liver X receptor/retinoid X receptor signaling is activated in the isoproterenol-challenged hearts treated with INSL6 protein. CONCLUSIONS: Endogenous Insl6 protein inhibits cardiac systolic dysfunction and cardiac fibrosis in angiotensin II- and isoproterenol-induced cardiac stress models. The administration of recombinant INSL6 protein could have utility for the treatment of heart failure and cardiac fibrosis. |
