Identification of monocyte-associated genes as predictive biomarkers of heart failure after acute myocardial infarction

Abstract

Background Acute myocardial infarction (AMI) is a major contributor of heart failure (HF). Peripheral blood mononuclear cells (PBMCs), mainly monocytes, are the essential initiators of AMI-induced HF. The powerful biomarkers for early identification of AMI patients at risk of HF remain elusive. We aimed to identify monocyte-related critical genes as predictive biomarkers for post-AMI HF. Methods We performed weighted gene co-expression network analysis (WGCNA) on transcriptomics of PBMCs from AMI patients who developed HF or did not. Functional enrichment analysis of genes in significant modules was performed via Metascape. Then we obtained the single-cell RNA-sequencing data of recruited monocytes/macrophages from AMI and control mice using the Scanpy and screened 381 differentially expressed genes (DEGs) between the two groups. We validated the expression changes of the 25 genes in cardiac macrophages from AMI mice based on bulk RNA-sequencing data and PBMCs data mentioned above. Results In our study, the results of WGCNA showed that two modules containing 827 hub genes were most significantly associated with post-AMI HF, which mainly participated in cell migration, inflammation, immunity, and apoptosis. There were 25 common genes between DEGs and hub genes, showing close relationship with inflammation and collagen metabolism. CUX1, CTSD and ADD3 exhibited consistent changes in three independent studies. Receiver operating characteristic curve analysis showed that each of the three genes had excellent performance in recognizing post-AMI HF patients. Conclusion Our findings provided a set of three monocyte-related biomarkers for the early prediction of HF development after AMI as well as potential therapeutic targets of post-AMI HF.

Biomarcadores Cardíacos como preditores do prognóstico na Insuficiência Cardíaca: uma Revisão Sistemática da Literatura / Cardiac Biomarkers as Predictors of Prognosis in Heart Failure: A Systematic Literature Review

“…A persistência de maus hábitos pode levar a principal alteração patológica relacionada a IC, o remodelamento miocárdico. Esse remodelamento é identificado como um processo crônico inflamatório associado a apoptose celular, hiper ativação de células do sistema imunológico, acumulo de células necróticas, fibrose intersticial do tecido miocárdico e também a hipertrofia dos miócitos (CHEN et al, 2021).…”

“…Foram identificados três biomarcadores importantes e que foram associados a progressão para IC após IAM sendo o CUX1, ADD3 e o CTSD os que demonstraram melhores desempenhos e identificação dos potenciais pacientes com risco de evoluir para insuficiência de câmara. Essa identificação precoce pode auxiliar no manejo clínico desses pacientes (CHEN et al, 2021).…”

Methylation-Driven Gene PLAU as a Potential Prognostic Marker for Differential Thyroid Carcinoma

“…We first submitted the list of methylation driver genes to Metascape and analyzed their GO and KEGG enrichment results ( Chen et al, 2021 ). After selecting the target genes, we also analyzed the KEGG enrichment results of the target genes with their associated differentially expressed genes.…”

The Identification and Validation of Hub Genes Associated with Acute Myocardial Infarction Using Weighted Gene Co-Expression Network Analysis

“…Weighted gene co-expression network analysis (WGCNA) is an effective technique for processing transcriptome data, as it clusters tightly connected genes into different modules and explores the correlation between modules and traits of interest; it does not only focus on the differentially expressed genes [6]. Scale-free co-expression network analysis using WGCNA has been conducted in most disease research [7][8][9].…”