{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T08:45:45Z","timestamp":1769849145497,"version":"3.49.0"},"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University","award":["JYHL2021MS10"],"award-info":[{"award-number":["JYHL2021MS10"]}]},{"name":"College Students' Innovation Training Program of Jining Medical University","award":["cx2024007z"],"award-info":[{"award-number":["cx2024007z"]}]},{"name":"College Students' Innovation Training Program of Jining Medical University","award":["cx2024135z"],"award-info":[{"award-number":["cx2024135z"]}]},{"name":"the Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University","award":["JYHL2021MS13"],"award-info":[{"award-number":["JYHL2021MS13"]}]},{"name":"the Incubation Fund for High-level Scientific Research Projects in Jining Medical University","award":["JYGC2023KJ003"],"award-info":[{"award-number":["JYGC2023KJ003"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The melanocortin-4 receptor (MC4R) is highly expressed in the hypothalamus, and mutations in this gene are closely associated with the development of hereditary obesity and early-onset severe obesity in humans.\n                    <jats:italic>Mc4r<\/jats:italic>\n                    has been shown to be involved in the development of dilated cardiomyopathy. However, the current system for the early diagnosis and treatment of heart disease is not well established. In this study, we analyzed the effects of\n                    <jats:italic>Mc4r<\/jats:italic>\n                    knockout on cardiac function, cardiomyocyte morphology, fibrosis, and apoptosis in mice. Moreover, we explored the possible early molecular mechanisms by which\n                    <jats:italic>Mc4r<\/jats:italic>\n                    affects cardiac dysfunction via transcriptome sequencing of cardiac cells combined with bioinformatics analysis. Although the overall heart does not show organic changes, our study suggested that cardiomyocytes already show early abnormal changes at the molecular level. The sequencing results revealed that the genes that were differentially expressed between the two groups of mice were enriched mainly in the p53 signaling pathway and the hypoxia-inducible factor 1 (HIF-1) signaling pathway. We screened 10 key target genes via a protein\u2013protein interaction (PPI) network and module analysis. Drugs targeting key genes were subsequently screened, and\n                    <jats:italic>angiotensinogen<\/jats:italic>\n                    (\n                    <jats:italic>Agt<\/jats:italic>\n                    ) and\n                    <jats:italic>Kit<\/jats:italic>\n                    were identified as potential drug targets. We analyze relevant data through bioinformatics to screen for signaling pathways and key hub genes that are enriched in differentially expressed genes (DEGs), as well as molecules targeting the hub genes, in order to provide ideas for early prevention of heart disease caused by\n                    <jats:italic>Mc4r<\/jats:italic>\n                    gene defects or related obesity.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0340465","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T18:27:57Z","timestamp":1769797677000},"page":"e0340465","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular remodeling of the myocardium in mice with melanocortin-4 receptor deletion before cardiac function impairment"],"prefix":"10.1371","volume":"21","author":[{"given":"Xiaomei","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanmin","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziming","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caiqin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhimin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haocheng","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linhui","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3939-273X","authenticated-orcid":true,"given":"Kai","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinxiang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"issue":"8","key":"pone.0340465.ref001","article-title":"Heart disease and stroke statistics\u20142022 update: a report from the American Heart Association","volume":"145","author":"CW Tsao","year":"2022","journal-title":"Circulation"},{"key":"pone.0340465.ref002","first-page":"1309","article-title":"Do we need diagnostic strategies enhanced with genetic information for ischemic heart disease?","author":"PY Marie","year":"2019"},{"issue":"1","key":"pone.0340465.ref003","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3390\/nu12010068","article-title":"Temporal Measures in Cardiac Structure and Function During the Development of Obesity Induced by Different Types of Western Diet in a Rat Model","volume":"12","author":"DF Vileigas","year":"2019","journal-title":"Nutrients"},{"issue":"4","key":"pone.0340465.ref004","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11886-022-01650-3","article-title":"Strategies for Imaging Metabolic Remodeling of the Heart in Obesity and Heart Failure","volume":"24","author":"A Haidar","year":"2022","journal-title":"Curr Cardiol Rep"},{"key":"pone.0340465.ref005","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fped.2017.00146","article-title":"Risk Factors, Prophylaxis, and Treatment of Venous Thromboembolism in Congenital Heart Disease Patients","volume":"5","author":"M Silvey","year":"2017","journal-title":"Front Pediatr"},{"issue":"9","key":"pone.0340465.ref006","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1080\/17434440.2019.1649133","article-title":"Magmaris resorbable magnesium scaffold for the treatment of coronary heart disease: overview of its safety and efficacy","volume":"16","author":"J Bennett","year":"2019","journal-title":"Expert Rev Med Devices"},{"key":"pone.0340465.ref007","doi-asserted-by":"crossref","unstructured":"Babu S, Vivek E, Famina K, Fida K, Aswathi P, Shanid M. Heart disease diagnosis using data mining technique. 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