Regulation of cardiac fibrosis in mice with TAC/DOCA-induced HFpEF by resistin-like molecule gamma and adenylate...

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a major subtype of heart failure with no current effective treatments.
• Cardiac fibrosis plays a critical role in HFpEF pathology, presenting a potential therapeutic target.

Purpose of the Study:

• To identify key fibrosis-related genes and pathways involved in the pathophysiology of HFpEF.
• To explore potential therapeutic targets for HFpEF by analyzing gene expression profiles.

Main Methods:

• Constructed a mouse model of HFpEF and analyzed gene expression profiles from the Gene Expression Omnibus database.
• Utilized single-sample Gene Set Enrichment Analysis (ssGSEA) for fibrosis-related pathways and cross-tabulation for differentially expressed genes (DEGs).
• Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, followed by in vivo validation of key genes.

Main Results:

• Myocardial fibrosis was significantly upregulated in HFpEF mice compared to controls.
• ssGSEA identified significant differences in nine fibrosis-related pathways in HFpEF myocardial tissue, with 112 of 798 DEGs linked to fibrosis.
• Resistin-like molecule gamma (Relmg) expression was significantly higher, and adenylate cyclase 1 (Adcy1) expression was significantly lower in HFpEF mouse hearts.

Conclusions:

• The study identified Relmg and Adcy1 as significantly dysregulated genes in HFpEF.
• Cardiac fibrosis, Relmg, and Adcy1 are suggested as potential therapeutic targets for treating HFpEF.