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| Status |
Public on May 31, 2018 |
| Title |
Protective effects of INSL6 on heart failure |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Background: The insulin/IGF/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 (Insl6-KO) 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-KO mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation hypertrophy. Cardiac dysfunction in the Insl6-KO 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 Lxr/ Rxr 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.
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| Overall design |
3 groups with 2 comparisons. Normal heart vs. heart treated with Iso, and heart treated with Iso vs. heart treated with Iso and INSL6 protein.
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| Contributor(s) |
Maruyama S, Wu C, Walsh K |
| Citation(s) |
29887522 |
| |
| Submission date |
Aug 14, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Chia-Ling Wu |
| E-mail(s) |
clwu@bu.edu
|
| Organization name |
Boston University
|
| Department |
Whitaker Cardiovascular Institute
|
| Lab |
Walsh
|
| Street address |
700Albany St
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17791 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [mogene20st_Mm_ENTREZG_17.1.0] |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA398211 |
