Xianwen Tang

Background: Epidemiological evidence indicates that up to 50% of systemic lupus erythematosus (SLE) patients exhibit cardiac involvement, suggesting a potential strong association between SLE and dilated cardiomyopathy (DCM). This study aims to identify SLE-related genes that may contribute to DCM development and to discover potential biomarkers for early DCM diagnosis in SLE patients.Methods: We obtained expression profile datasets for dilated cardiomyopathy DCM and SLE from the Gene Expression Omnibus (GEO) database. Through differential expression analysis and weighted gene co-expression network analysis (WGCNA), we screened for candidate biomarkers shared between DCM and SLE and constructed a diagnostic nomogram. The diagnostic performance and effectiveness of the nomogram were evaluated using external datasets and qPCR. Additionally, we performed single-gene set enrichment analysis (GSEA) on key genes to elucidate their potential roles in SLE-related DCM. Finally, we applied the CIBERSORT algorithm to assess immune cell infiltration in both DCM and SLE patients.Results: Through DEG and WGCNA in the DCM and SLE datasets, we identified a total of 141 key module genes and 24 commonly expressed differentially expressed genes. Enrichment analysis revealed that these 24 genes were primarily involved in inflammation, cell apoptosis, and immune regulation. Through machine learning algorithms and dataset validation, we further identified the HERC6 and IFI44L genes as important diagnostic markers for SLE-related DCM. Experimental validation supports the key role of HERC6, IFI44L, and RSAD2 in SLE-related cardiac dysfunction. Additionally, we developed a nomogram for DCM based on these two genes, and the results showed that both genes exhibited AUC values greater than 0.84. Simultaneously, single-GSEA and immune infiltration analysis indicated immune dysfunction in both DCM and SLE, with both HERC6 and IFI44L significantly associated with immune cell infiltration. Furthermore, connectivity map (cMAP) analysis identified α-linolenic acid as a potential therapeutic agent for treating DCM.Conclusion: Our study identifies HERC6 and IFI44L as diagnostic markers for DCM in SLE and suggests α-linolenic acid as a potential therapeutic agent.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by hypertension, metabolic disorders, and impaired diastolic function, with limited therapeutic options. Recent studies have highlighted the role of ferroptosis in the pathogenesis of HFpEF, and the inhibition of ferroptosis occurrence can significantly improve cardiac function. Limonin, a bioactive ingredient derived from citrus fruits, has been confirmed to exert potential anti-inflammatory and antioxidant effects in some cardiovascular diseases. This study aims to investigate the therapeutic effects of limonin on HFpEF and the underlying mechanisms of inhibiting ferroptosis. HFpEF mice were established by a combination of Nω-nitro-L-arginine methyl ester and a high-fat diet for 6 weeks. Subsequently, the HFpEF mice were treated with empagliflozin or limonin via oral gavage for an additional 6 weeks. Limonin curbed body weight gain and improved metabolic disorders and hypertension. Limonin also ameliorated concentric cardiac hypertrophy and diastolic dysfunction. Transcriptomics and metabolomics analyses revealed that limonin regulated ferroptosis-related pathways and lipid peroxidation. In vivo, limonin improved mitochondrial morphology, reduced cardiac Fe²⁺ levels and ferroptosis markers such as ROS, 4-HNE and MDA, and increased GSH levels, thereby enhancing antioxidant capacity. Mechanistically, limonin regulated the P53/SLC7A11/GPX4 signaling pathway, promoted the nuclear translocation of Nrf2 (its upstream signaling molecule), and subsequently activated its downstream antioxidant elements, ultimately inhibiting ferroptosis. Furthermore, limonin decreased the expressions of ACSL4, COX2, and ALOXs, which reduced the accumulation of lipid peroxides. These results demonstrate that limonin ameliorates HFpEF by targeting ferroptosis via modulation of the Nrf2/SLC7A11/GPX4 axis, providing a novel strategy for HFpEF treatment.

Background: As the complexity and diversity of the percutaneous coronary intervention (PCI) are being explored and reported, burgeoning research has progressed in this field. However, there is no comprehensive analysis available on PCI-related studies published in the literature. This study aimed to analyze and visualize the changes of scientific output regarding prognosis of coronary heart disease (CHD) after PCI over the past 20 years and to reveal the knowledge domain and development trends in this field by using CiteSpace software. Methods: Relevant articles published over the period 2004–2022 were retrieved from the Web of Science Core Collection database. After manual selection, qualified documents were included and recorded with the information of their title, abstract, keyword, author, descriptor, citation, identifier, publishing year and publishing organization. We transferred the data to CiteSpace V5.8.R2 (Version 5.8.R2) to draw knowledge maps and to conduct co-occurrence analysis, cluster analysis, timeline analysis, burst term detection and citation analysis. Results: A total of 14,699 literature records were found relating prognosis of CHD after PCI in the past 20 years (2004–2022), including 14,212 original articles and reviews, and they were published in 153 different journals. Publication production has increased annually and a total of 1182 authors, 796 institutes and 147 countries have contributed to these publications. Moreover, the most representative author was Gregg W Stone from the CardioVascular Research Foundation (CVRF) with 368 publications, whose team mainly focused on exploring the efficacy and safety of revascularization and the characteristics of susceptible population. The global productivity ranking was led by the USA with 3326 published papers, followed by Italy (n = 1355), Japan (n = 1080), China (n = 1075) and Germany (n = 937). And the keywords of these publications were “percutaneous coronary intervention” (n = 2271), “outcome” (n = 1756), “mortality” (n = 1730) and “impact” (n = 1334). Other commonly-used words were “predictor” (n = 1324), “intervention” (n = 1310), “angioplasty” (n = 1299), “risk” (n = 1144), “acute myocardial infarction” (n = 1136) and “artery disease” (n = 1098). Cluster analysis showed that 15 high connected clusters were generated with a modularity Q of 0.831 and a weighted mean silhouette of 0.9388 by applying the log-likelihood ratio algorithm, and the top 5 clusters were #0 optical coherence tomography, #1 dual antiplatelet therapy, #2 bleeding, #3 clopidogrel and #4 thrombus aspiration. Furthermore, the frontiers in the field of prognosis of CHD after PCI mainly involved “decision making”, “reperfusion”, “angioplasty”, “balloon”, “unstable angina”, “dual antiplatelet therapy”, “cardiac surgical score”, “restenosis”, “reperfusion”, “thrombolytic therapy”, etc. Conclusions: To sum up, efficacy and safety of different types of stents, the risk factors of restenosis and thrombotic events after PCI, early risk assessment, and secondary prevention and complications of patients with CHD after PCI were research hotspots and frontier topics in the area by bibliometric analysis. The results could provide a comprehensive overview of the research hotspots and frontier topics relating prognosis of CHD after PCI, promoting a better understanding of the knowledge domain and development trends in this field during the past 20 years.