Molecular remodeling of the myocardium in mice with melanocortin-4 receptor deletion before cardiac function...

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Genetics

Background:

• Melanocortin-4 receptor (MC4R) mutations are linked to obesity.
• MC4R plays a role in dilated cardiomyopathy, but early diagnosis and treatment remain challenging.
• Understanding MC4R's role in cardiac dysfunction is crucial for developing early interventions.

Purpose of the Study:

• To investigate the effects of Mc4r knockout on cardiac function and cardiomyocyte characteristics in mice.
• To explore the early molecular mechanisms underlying Mc4r-associated cardiac dysfunction using transcriptome sequencing and bioinformatics.
• To identify potential therapeutic targets for preventing heart disease related to MC4R defects.

Main Methods:

• Analysis of cardiac function, cardiomyocyte morphology, fibrosis, and apoptosis in Mc4r knockout mice.
• Transcriptome sequencing of cardiac cells to identify differentially expressed genes (DEGs).
• Bioinformatics analysis, including protein-protein interaction (PPI) network and module analysis, to identify key genes and pathways.

Main Results:

• Mc4r knockout mice exhibited early molecular abnormalities in cardiomyocytes, despite no gross organic heart changes.
• DEGs were significantly enriched in the p53 and hypoxia-inducible factor 1 (HIF-1) signaling pathways.
• Angiotensinogen (Agt) and Kit were identified as potential drug targets through PPI network and drug screening.

Conclusions:

• Mc4r deficiency induces subtle, early molecular changes in cardiomyocytes that precede overt cardiac pathology.
• The p53 and HIF-1 signaling pathways are implicated in Mc4r-associated cardiac dysfunction.
• Agt and Kit represent promising targets for the early prevention of heart disease in individuals with MC4R gene defects or obesity.