The First Affiliated Hospital of Chongqing Medical University, China.
Department of Cardiology, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, China.
FEBS Open Bio. 2024 Jul;14(7):1101-1115. doi: 10.1002/2211-5463.13813. Epub 2024 May 6.
Heart failure with preserved ejection fraction (HFpEF) is one of the major subtypes of heart failure (HF) and no effective treatments for this common disease exist to date. Cardiac fibrosis is central to the pathology of HF and a potential avenue for the treatment of HFpEF. To explore key fibrosis-related genes and pathways in the pathophysiological process of HFpEF, a mouse model of HFpEF was constructed. The relevant gene expression profiles were downloaded from the Gene Expression Omnibus database, and single-sample Gene Set Enrichment Analysis (ssGSEA) was performed targeting fibrosis-related pathways to explore differentially expressed genes (DEGs) in healthy control and HFpEF heart tissues with cross-tabulation analysis of fibrosis-related genes. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the identified fibrosis-related genes. The two most significant DEGs were selected, and further validation was conducted in HFpEF mice. The results indicated that myocardial fibrosis was significantly upregulated in HFpEF mice compared to healthy controls, while the ssGSEA results revealed significant differences in the enrichment of nine fibrosis-related pathways in HFpEF myocardial tissue, with 112 out of 798 DEGs being related to fibrosis. The in vivo results demonstrated that expression levels of resistin-like molecule gamma (Relmg) and adenylate cyclase 1 (Adcy1) in the heart tissues of HFpEF mice were significantly higher and lower, respectively, compared to healthy controls. Taken together, these results suggest that Relmg and Acdy1 as well as the fibrosis process may be potential targets for HFpEF treatment.
射血分数保留型心力衰竭（HFpEF）是心力衰竭（HF）的主要亚型之一，迄今为止，尚无针对这种常见疾病的有效治疗方法。心肌纤维化是 HF 病理生理学的核心，也是治疗 HFpEF 的潜在途径。为了探讨 HFpEF 病理生理过程中与纤维化相关的关键基因和途径，构建了 HFpEF 小鼠模型。从基因表达综合数据库下载相关基因表达谱，针对纤维化相关途径进行单样本基因集富集分析（ssGSEA），采用纤维化相关基因的交叉制表分析，探讨健康对照和 HFpEF 心脏组织中差异表达基因（DEGs）。对鉴定出的与纤维化相关的基因进行基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路富集分析。选择两个最重要的 DEG 进一步在 HFpEF 小鼠中进行验证。结果表明，与健康对照组相比，HFpEF 小鼠心肌纤维化明显上调，而 ssGSEA 结果显示 HFpEF 心肌组织中 9 个纤维化相关通路的富集存在显著差异，其中 798 个 DEG 中有 112 个与纤维化相关。体内结果表明，HFpEF 小鼠心脏组织中抵抗素样分子γ（Relmg）和腺苷酸环化酶 1（Adcy1）的表达水平明显升高和降低。综上所述，这些结果表明 Relmg 和 Acdy1 以及纤维化过程可能是 HFpEF 治疗的潜在靶点。
