{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:55:09Z","timestamp":1787018109414,"version":"build-2736575974"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,2,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The melanocortin 1 receptor (MC1R) is abundantly expressed in the skin and leukocytes, where it regulates skin pigmentation and inflammatory responses. Recently, MC1R was also found in the heart, but its functional role has remained unknown. We aimed to investigate whether MC1R is involved in the regulation of pathological or physiological cardiac remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Recessive yellow mice, as a model of global MC1R deficiency, and cardiomyocyte\u2010specific MC1R knockout mice were subjected to transverse aortic constriction or voluntary wheel running to induce pathological or physiological cardiac hypertrophy, respectively. Mice were phenotyped for cardiac structure and function by echocardiography, histology, and quantitative PCR analysis. H9c2 cells and neonatal mouse ventricular cardiac myocytes were used as in\u00a0vitro models to investigate the effects of pharmacological MC1R activation on hypertrophy\u2010related responses. We found that the expression of MC1R progressively declines in the failing mouse heart. MC1R recessive yellow mice showed blunted hypertrophic response to transverse aortic constriction\u2013induced pressure overload and exercise training. This phenotype was recapitulated in MC1R knockout mice, demonstrating that MC1R deficiency specifically in cardiomyocytes is responsible for the antihypertrophic effect. However, MC1R knockout mice subjected to pressure overload showed left ventricular dilatation that was associated with reduced ejection fraction and changes in left ventricular diastolic function. At the molecular level, the mRNA expression of myosin heavy chain \u03b2 was upregulated in the hearts of MC1R knockout mice. In contrast, selective activation of MC1R promoted hypertrophic responses in cultured cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiomyocyte\u2010specific MC1R deficiency attenuates physiological and pathological cardiac hypertrophy in mice, while pharmacological activation of MC1R promotes cardiomyocyte hypertrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.037961","type":"journal-article","created":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T05:32:41Z","timestamp":1738992761000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Melanocortin 1 Receptor Regulates Pathological and Physiological Cardiac Remodeling"],"prefix":"10.1161","volume":"14","author":[{"given":"Anni","family":"Suominen","sequence":"first","affiliation":[{"name":"Research Centre for Integrative Physiology &amp; Pharmacology, Institute of Biomedicine University of Turku Finland"},{"name":"Drug Research Doctoral Programme (DRDP) University of Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aino","family":"Suni","sequence":"additional","affiliation":[{"name":"Research Centre for Integrative Physiology &amp; Pharmacology, Institute of Biomedicine University of Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saku","family":"Ruohonen","sequence":"additional","affiliation":[{"name":"Research Centre for Integrative Physiology &amp; Pharmacology, Institute of Biomedicine University of Turku 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