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
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
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
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
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.
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