Wenqiang Chen

Background: Angiogenesis and coronary collateral circulation (CCC) formation promote cardiac repair following severe coronary stenosis (SCS) or myocardial infarction (MI). Angiopoietin-like protein 7 (ANGPTL7) is a secreted protein associated with angiogenesis, but its role in CCC formation remains unclear.Objective: The aim of this study was to investigate the role of ANGPTL7 in angiogenesis and evaluate the predictive value of serum ANGPTL7 in CCC formation and the prognosis of patients with SCS.Materials and methods: The RNA sequencing was performed on myocardial tissues of mice to analyze the alterations of angiogenesis-related genes after MI. 100 patients with angiographically proven SCS and 36 controls were enrolled and retrospectively followed up. Serum ANGPTL7 was measured by enzyme-linked immunosorbent assays (ELISA). Human umbilical vein endothelial cells (HUVECs) and exogenous human recombinant ANGPTL7 protein were applied in assays including CCK-8, scratch, tube formation, cell immunofluorescence and western blot to demonstrate the proangiogenic effect of ANGPTL7. Gene Set Enrichment Analysis (GSEA) was used to perform KEGG pathway enrichment analysis on downstream mechanisms by which ANGPTL7 promoted angiogenesis.Results: The transcriptional level of Angptl7 was upregulated in ischemic myocardial tissues of MI mice, and its serum levels increased in both mice post-MI and patients with SCS. Spearman correlation analysis indicated that serum ANGPTL7 levels were positively correlated to CCC grades (r = 0.518, P < 0.001). Kaplan–Meier curves showed a higher serum ANGPTL7 was associated with a lower incidence of major adverse cardiovascular events (MACE) in patients with SCS (Log-rank test, P = 0.002). Cox proportional hazards regression analyses showed that serum ANGPTL7 level was remained a protective factor after adjusting for different covariates. Time-dependent receiver-operating characteristics (ROC) curves further explored the prognostic value of ANGPTL7, with the area under the curve (AUC) of 0.77 at 1 year, 0.70 at 2 years and 0.85 at 3 years. Additionally, ANGPTL7 enhanced endothelial cell proliferation, migration and capillary-like structure formation, indicating a proangiogenic effect in vitro.Conclusion: ANGPTL7 serves as a predictive biomarker for CCC levels and the prognosis of patients with SCS, which probably attributed to its proangiogenic properties.

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Background: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. Methods: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan–Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. Results: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120–134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 − 1.10, p = 0.690). Conclusions: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.

Background: At present, there is a paucity of research on the link between Crohn’s disease (CD) and atrial fibrillation (AF). Nevertheless, both ailments are thought to entail inflammatory and autoimmune processes, and emerging evidence indicates that individuals with CD may face an elevated risk of AF. To shed light on this issue, our study seeks to explore the possibility of shared genes, pathways, and immune cells between these two conditions. Methods: We retrieved the gene expression profiles of both CD and AF from the Gene Expression Omnibus (GEO) database and subjected them to analysis. Afterward, we utilized the weighted gene co-expression network analysis (WGCNA) to identify shared genes, which were then subjected to further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, we employed a rigorous analytical approach by screening hub genes through both least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM), and subsequently constructing a receiver operating characteristic (ROC) curve based on the screening outcomes. Finally, we utilized single-sample gene set enrichment analysis (ssGSEA) to comprehensively evaluate the levels of infiltration of 28 immune cells within the expression profile and their potential association with the shared hub genes. Results: Using the WGCNA method, we identified 30 genes that appear to be involved in the pathological progression of both AF and CD. Through GO enrichment analysis on the key gene modules derived from WGCNA, we observed a significant enrichment of pathways related to major histocompatibility complex (MHC) and antigen processing. By leveraging the intersection of LASSO and SVM algorithms, we were able to pinpoint two overlapping genes, namely CXCL16 and HLA-DPB1. Additionally, we evaluated the infiltration of immune cells and observed the upregulation of CD4⁺ and CD8⁺ T cells, as well as dendritic cells in patients with AF and CD. Conclusions: By employing bioinformatics tools, we conducted an investigation with the objective of elucidating the genetic foundations that connect AF and CD. This study culminated in the identification of CXCL16 and HLA-DPB1 as the most substantial genes implicated in the development of both disorders. Our findings suggest that the immune responses mediated by CD4⁺ and CD8⁺ T cells, along with dendritic cells, may hold a crucial role in the intricate interplay between AF and CD.