scholarly journals Association of Circulating, Inflammatory-Response Exosomal mRNAs With Acute Myocardial Infarction

2021 ◽  
Vol 8 ◽  
Author(s):  
Guo-dong He ◽  
Yu-qing Huang ◽  
Lin Liu ◽  
Jia-yi Huang ◽  
Kenneth Lo ◽  
...  

Background: Although many cardiovascular disease studies have focused on the microRNAs of circulating exosomes, the profile and the potential clinical diagnostic value of plasma exosomal long RNAs (exoLRs) are unknown for acute myocardial infarction (AMI).Methods: In this study, the exoLR profile of 10 AMI patients, eight stable coronary artery disease (CAD) patients, and 10 healthy individuals was assessed by RNA sequencing. Bioinformatic approaches were used to investigate the characteristics and potential clinical value of exoLRs.Results: Exosomal mRNAs comprised the majority of total exoLRs. Immune cell types analyzed by CIBERSORT showed that neutrophils and monocytes were significantly enriched in AMI patients, consistent with clinical baseline values. Biological process enrichment analysis and co-expression network analysis demonstrated neutrophil activation processes to be enriched in AMI patients. Furthermore, two exosomal mRNAs, ALPL and CXCR2, were identified as AMI biomarkers that may be useful for evaluation of the acute inflammatory response mediated by neutrophils.Conclusions: ExoLRs were assessed in AMI patients and found to be associated with the acute inflammatory response mediated by neutrophils. Exosomal mRNAs, ALPL and CXCR2, were identified as potentially useful biomarkers for the study of AMI.

2020 ◽  
Author(s):  
Guo-dong HE ◽  
Yu-qing HUANG ◽  
Lin LIU ◽  
Jia-yi HUANG ◽  
Kenneth Lo ◽  
...  

Abstract Background Although many cardiovascular disease studies have focused on the characteristics of microRNAs in circulating exosomes, the profile and the potential clinical diagnostic value of plasma exosomal long RNAs (exoLRs) in acute myocardial infarction (AMI) is still unknown.Methods In this study, exosomes isolation and RNA sequencing were applied to achieve the circulating exoLRs profile of 10 AMI patients, 8 stable coronary artery disease (CAD) patients, and 10 healthy individuals. Bioinformatics approaches were used to investigate the features and potential clinical value of exoLRs.Results Each sample from 2 mL of plasma could reliably achieve more than 8000 exosomal messenger RNAs (mRNAs) making up a majority of the total exoLRs. Immune cell types analyzed by CIBERSORT showed that neutrophils and monocytes were significantly enriched in the AMI group compared to healthy individuals and the CAD group which were consistent with the clinical baseline characteristics. Similarly, the biological processes enrichment analyses of different exosomal mRNAs and co-expression network analysis both indicated that neutrophils activation associated processes were also significantly enriched in the AMI group. We further identified two exosomal mRNA ALPL and CXCR2 which might be served as potential biomarkers with high diagnostic efficiency through co-expression network analysis and receiver operating characteristic curve (ROC).Conclusions In summary, our study explored the alteration of exoLRs in the AMI patients which might associate with the acute inflammatory response mediated by neutrophils. We found that exosomal mRNAs ALPL and CXCR2 might be potentially useful for AMI diagnosis.


Pteridines ◽  
2021 ◽  
Vol 32 (1) ◽  
pp. 79-92
Author(s):  
Dongmei Wei ◽  
Rui Li ◽  
Tao Si ◽  
Hankang He ◽  
Wei Wu

Abstract Acute myocardial infarction (AMI) is the most severe manifestation of coronary artery disease. Considerable efforts have been made to elucidate its etiology and pathology, but the genetic factors that play a decisive role in the occurrence of AMI are still unclear. To determine the molecular mechanism of the occurrence and development of AMI, four microarray datasets, namely, GSE29111, GSE48060, GSE66360, and GSE97320, were downloaded from the Gene Expression Omnibus (GEO) database. We analyzed the four GEO datasets to obtain the differential expression genes (DEGs) of patients with AMI and patients with non-AMI and then performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-protein interaction (PPI) network analysis. A total of 41 DEGs were identified, including 39 upregulated genes and 2 downregulated genes. The enriched functions and pathways of the DEGs included the inflammatory response, neutrophil chemotaxis, immune response, extracellular space, positive regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor activity, response to lipopolysaccharide, receptor for advanced glycation end products (RAGE) receptor binding, innate immune response, defense response to bacterium, and receptor activity. The cytoHubba plug-in in Cytoscape was used to select the most significant hub gene from the PPI network. Ten hub genes were identified, and GO enrichment analysis revealed that these genes were mainly enriched in inflammatory response, neutrophil chemotaxis, immune response, RAGE receptor binding, and extracellular region. In conclusion, this study integrated four datasets and used bioinformatics methods to analyze the gene chips of AMI samples and control samples and identified DEGs that may be involved in the occurrence and development of AMI. The study provides reliable molecular biomarkers for AMI screening, diagnosis, and prognosis.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Liu-An Zhuo ◽  
Yi-Tao Wen ◽  
Yong Wang ◽  
Zhi-Fang Liang ◽  
Gang Wu ◽  
...  

Abstract Background Long noncoding RNAs (lncRNAs) are involved in numerous physiological functions. However, their mechanisms in acute myocardial infarction (AMI) are not well understood. Methods We performed an RNA-seq analysis to explore the molecular mechanism of AMI by constructing a lncRNA-miRNA-mRNA axis based on the ceRNA hypothesis. The target microRNA data were used to design a global AMI triple network. Thereafter, a functional enrichment analysis and clustering topological analyses were conducted by using the triple network. The expression of lncRNA SNHG8, SOCS3 and ICAM1 was measured by qRT-PCR. The prognostic values of lncRNA SNHG8, SOCS3 and ICAM1 were evaluated using a receiver operating characteristic (ROC) curve. Results An AMI lncRNA-miRNA-mRNA network was constructed that included two mRNAs, one miRNA and one lncRNA. After RT-PCR validation of lncRNA SNHG8, SOCS3 and ICAM1 between the AMI and normal samples, only lncRNA SNHG8 had significant diagnostic value for further analysis. The ROC curve showed that SNHG8 presented an AUC of 0.850, while the AUC of SOCS3 was 0.633 and that of ICAM1 was 0.594. After a pairwise comparison, we found that SNHG8 was statistically significant (PSNHG8-ICAM1 = 0.002; PSNHG8-SOCS3 = 0.031). The results of a functional enrichment analysis of the interacting genes and microRNAs showed that the shared lncRNA SNHG8 may be a new factor in AMI. Conclusions Our investigation of the lncRNA-miRNA-mRNA regulatory networks in AMI revealed a novel lncRNA, lncRNA SNHG8, as a risk factor for AMI and expanded our understanding of the mechanisms involved in the pathogenesis of AMI.


2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110196
Author(s):  
Heyu Meng ◽  
Jianjun Ruan ◽  
Xiaomin Tian ◽  
Lihong Li ◽  
Weiwei Chen ◽  
...  

Objective This study aimed to investigate whether differential expression of the retinoic acid receptor-related orphan receptor A ( RORA) gene is related to occurrence of acute myocardial infarction (AMI). Methods This was a retrospective study. White blood cells of 93 patients with acute myocardial infarction and 74 patients with stable coronary artery disease were collected. Reverse transcription quantitative polymerase chain reaction and western blotting were used to measure RORA mRNA and protein expression, respectively. Results RORA mRNA expression levels in peripheral blood leukocytes in patients with AMI were 1.57 times higher than those in patients with stable coronary artery disease. Protein RORA levels in peripheral blood of patients with AMI were increased. Binary logistic regression analysis showed that high expression of RORA was an independent risk factor for AMI, and it increased the risk of AMI by 2.990 times. Conclusion RORA expression levels in patients with AMI is significantly higher than that in patients with stable coronary artery disease. High expression of RORA is related to AMI and it may be an independent risk factor for AMI.


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