α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor
Suominen, Anni; Saldo Rubio, Guillem; Ruohonen, Saku; Szabó, Zoltán; 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 (2024-03-07)
John Wiley & Sons
07.03.2024
Suominen, A., Saldo Rubio, G., Ruohonen, S., Szabó, Z., Pohjolainen, L., Ghimire, B., Ruohonen, S. T., Saukkonen, K., Ijas, J., Skarp, S., Kaikkonen, L., Cai, M., Wardlaw, S. L., Ruskoaho, H., Talman, V., Savontaus, E., Kerkelä, R., & Rinne, P. (2024). α-Melanocyte-stimulating hormone alleviates pathological cardiac remodeling via melanocortin 5 receptor. EMBO Reports, 25(4), 1987–2014. https://doi.org/10.1038/s44319-024-00109-6
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© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence ,unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiverhttp://creativecommons.org/public-domain/zero/1.0/applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202404152715
https://urn.fi/URN:NBN:fi:oulu-202404152715
Tiivistelmä
Abstract
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.
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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- Avoin saatavuus [37744]
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