线粒体基因NME6作为心力衰竭免疫调节因子的鉴定与分析

Abstract

Background: Heart failure (HF) is characterized by mitochondrial dysfunction and immune dysregulation. However, the underlying molecular mechanisms remain unclear. Functional enrichment analyses study aimed to identify key mitochondrial genes involved in HF pathogenesis and to explore their association with immune cell infiltration. Methods: Differentially expressed genes related to HF were identified and subjected to functional enrichment analyses. Summary data-based Mendelian randomization (SMR) was used to evaluate the diagnostic potential of candidate genes. Immune cell infiltration analysis was performed to assess associations between gene expression and immune profiles. Single-cell RNA sequencing data (GSE145154) were analyzed to determine cell-specific expression patterns. A transverse aortic constriction (TAC)-induced HF mouse model was established, and cardiac function was assessed by echocardiography. Histopathological analyses were conducted to evaluate myocardial injury, fibrosis, and apoptosis. Immune cell populations were further examined in vivo. Results: Functional enrichment analysis revealed that HF-related genes were significantly associated with mitochondrial organization and pathways such as mechanistic target of rapamycin (mTOR) signaling and cardiomyopathy. SMR analysis identified NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) and NME/NM23 nucleoside diphosphate kinase 6 (NME6) as having diagnostic relevance. Immune infiltration analysis showed correlations between these genes and immune cell populations. Single-cell RNA sequencing revealed that NME6 was predominantly expressed in T cells and neutrophils, indicating potentially important significance. Clinical data suggested that brain natriuretic peptide (BNP), C-reactive protein (CRP), neutrophils, monocytes, and inflammatory factor levels tended to increase with HF severity. Echocardiography determined that in HF mice, NME6 knockdown lessened the left