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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.
Afiliação
  • Suominen A; Research Centre for Integrative Physiology & Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
  • Saldo Rubio G; Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.
  • Ruohonen S; Research Centre for Integrative Physiology & Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
  • Szabó Z; Research Centre for Integrative Physiology & Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
  • Pohjolainen L; Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland.
  • Ghimire B; Drug Research Program and Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
  • Ruohonen ST; Institute for Molecular Medicine Finland (FIMM), HiLIFE Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
  • Saukkonen K; Faculty of Medicine, University of Turku, Turku, Finland.
  • Ijas J; Research Centre for Integrative Physiology & Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
  • Skarp S; Research Centre for Integrative Physiology & Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
  • Kaikkonen L; Research Centre for Integrative Physiology & Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
  • Cai M; Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland.
  • Wardlaw SL; Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland.
  • Ruskoaho H; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
  • Talman V; Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Savontaus E; Drug Research Program and Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
  • Kerkelä R; Drug Research Program and Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
  • Rinne P; Research Centre for Integrative Physiology & Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland.
EMBO Rep ; 25(4): 1987-2014, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38454158
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Alfa-MSH / Remodelação Ventricular Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Alfa-MSH / Remodelação Ventricular Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article