A1 Refereed original research article in a scientific journal
α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor
Authors: Suominen Anni, Saldo Rubio Guillem, Ruohonen Saku, Szabó Zoltan, Pohjolainen Lotta, Ghimire Bishwa, Ruohonen Suvi T., Saukkonen Karla, Ijas Jani, Skarp Sini, Kaikkonen Leena, Cai Minying, Wardlaw Sharon L., Ruskoaho Heikki, Talman Virpi, Savontaus Eriika, Kerkelä Risto, Rinne Petteri
Publisher: Springer Nature
Publication year: 2024
Journal: EMBO Reports
Journal name in source: EMBO Reports
Volume: 25
Issue: 4
First page : 1987
Last page: 2014
eISSN: 1469-3178
DOI: https://doi.org/10.1038/s44319-024-00109-6
Web address : https://doi.org/10.1038/s44319-024-00109-6
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/387705040
α-Melanocyte-stimulating hormone (α-MSH) regulates diverse physiological functions by activating melanocortin receptors (MC-R). However, the role of α-MSH and its possible target receptors in the heart remain completely unknown. Here we investigate whether α-MSH could be involved in pathological cardiac remodeling. We found that α-MSH was highly expressed in the mouse heart with reduced ventricular levels after transverse aortic constriction (TAC). Administration of a stable α-MSH analog protected mice against TAC-induced cardiac hypertrophy and systolic dysfunction. In vitro experiments revealed that MC5-R in cardiomyocytes mediates the anti-hypertrophic signaling of α-MSH. Silencing of MC5-R in cardiomyocytes induced hypertrophy and fibrosis markers in vitro and aggravated TAC-induced cardiac hypertrophy and fibrosis in vivo. Conversely, pharmacological activation of MC5-R improved systolic function and reduced cardiac fibrosis in TAC-operated mice. In conclusion, α-MSH is expressed in the heart and protects against pathological cardiac remodeling by activating MC5-R in cardiomyocytes. These results suggest that analogs of naturally occurring α-MSH, that have been recently approved for clinical use and have agonistic activity at MC5-R, may be of benefit in treating heart failure.
Downloadable publication This is an electronic reprint of the original article. |  |
