A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor
Tekijät: 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
Kustantaja: Springer Nature
Julkaisuvuosi: 2024
Lehti: EMBO Reports
Tietokannassa oleva lehden nimi: EMBO Reports
Vuosikerta: 25
Numero: 4
Aloitussivu: 1987
Lopetussivu: 2014
eISSN: 1469-3178
DOI: https://doi.org/10.1038/s44319-024-00109-6
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1038/s44319-024-00109-6
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/387705040
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
