scholarly journals Identification of Immune Activation-Related Biomarkers in Acute Myocardial Infarction (AMI) by Bioinformatic Analysis and Clinical Validation

Author(s):  
Xiangwen Xi ◽  
Yu Chen ◽  
Li Yu ◽  
Meiling Sun ◽  
Zhipeng Qian ◽  
...  

Abstract Background: Although reperfusion therapy is widely performed in patients with acute myocardial infarction (AMI), the residual risk of poor outcomes remains substantial. The immune system plays an important role in AMI, and therapies targeting immune cells have proved effective in improving prognosis after AMI. However, the activation and regulation of immune signaling pathways during AMI have not been systematically studied.Objective: This study aimed to reveal the activation status of immune-related signals and the immune status after AMI.Methods and results: Three publicly available datasets (GSE48060, GSE66360, and GSE97320) from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs) using peripheral blood tissue samples from 22 AMI patients and 22 individuals without AMI. Subsequent weighted gene correlation network analysis (WGCNA) was performed for CD4+ T cells, macrophages, and regulatory T cells, and the 387 genes with the most significant correlations with the three immune cells were identified. Then, we intersected the 192 DEGs with 387 genes from WGCNA to reveal , a total of 151 overlapping genes. Protein-protein interaction (PPI) network analysis was performed to identify the hub genes. Furthermore, we recruited 44 patients and collected blood samples to validate the stability and reliability of the predicted hub tragets TLR2, TLR4, TLR8, MMP-9 and TYROBP using qRT-PCR assay.Conclusions: The immune-related genes TLR2, TLR4, TLR8, MMP9 and TYROBP may be potential biomarkers to identify immune signal activation after AMI, therefore providing information for the evaluation of both immune status and early intervention.

2020 ◽  
Author(s):  
Zhiwen Ding ◽  
Zhaohui Hu ◽  
Xiangjun Ding ◽  
Yuyao Ji ◽  
Guiyuan li ◽  
...  

Abstract Background: Acute myocardial infarction (AMI) is a common cause of death in many countries. Analyzing the potential biomarkers of AMI is crucial to understanding the molecular mechanism of disease. However, specific diagnostic biomarkers have not been fully elucidated, and candidate regulatory targets for AMI have not been determined.Methods: In this study, AMI gene chip data GSE48060, blood samples from normal cardiac function controls (n = 21) and AMI patients (n = 26) were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) of AMI and control group were identified with Online tool GEO2R. the genes co-expressed with were found. The co-expression network of DEGs was analyzed by calculating the Pearson correlation coefficient of all gene pairs, MR screening and cutoff threshold screening. Then, GO database was used to analyze the function and pathway enrichment of genes in the most important modules. KEGG DISEASE and BioCyc were used to analyze the hub gene in the module to determine important sub-pathways. In addition, the expression of hub genes were certified by RT-qPCR in AMI and control specimens.Results: This study identified 52 DEGs, including 26 up-regulated genes and 26 down-regulated genes. Co-expression network analysis of 52 DEGs revealed that there are mainly three up-regulated genes (AKR1C3, RPS24 and P2RY12) and three down-regulated genes (ACSL1, B3GNT5 and MGAM) as key hub genes in the co-expression network. Furthermore, GO enrichment analysis was performed on all AMI co-expression network genes and found to be functionally enriched mainly in RAGE receptor binding and negative regulation of T cell cytokine production. In addition, through KEGG DISEASE and BioCyc analysis, the functions of genes RPS24 and P2RY12 were enriched in cardiovascular diseases, AKR1C3 was enriched in cardenolide biosynthesis, MGAM was enriched in glycogenolysis, B3GNT5 was enriched in glycosphingolipids biosynthesis, and ACSL1 enriched in icosapentaenoate biosynthesis II. Conclusion: The hub genes AKR1C3, RPS24, P2RY12, ACSL1, B3GNT5 and MGAM are potential targets of AMI and have potential application value in the diagnosis of AMI.


2012 ◽  
Vol 8 (1) ◽  
pp. 60 ◽  
Author(s):  
Zuzana Kaifoszova ◽  
Petr Widimsky ◽  
◽  

Primary percutaneous coronary intervention (PPCI) is recommended by the European Society of Cardiology (ESC) treatment guidelines as the preferred treatment for ST-elevation acute myocardial infarction (STEMI) whenever it is available within 90–120 minutes of the first medical contact. A survey conducted in 2008 in 51 ESC countries found that the annual incidence of hospital admissions for acute myocardial infarction is around 1,900 patients per million population, with an incidence of STEMI of about 800 per million. It showed that STEMI patients’ access to reperfusion therapy and the use of PPCI or thrombolysis (TL) vary considerably between countries. Northern, western and central Europe already have well-developed PPCI services, offering PPCI to 60–90 % of all STEMI patients. Southern Europe and the Balkans are still predominantly using TL. Where this is the case, a higher proportion of patients are left without any reperfusion treatment. The survey concluded that a nationwide PPCI strategy results in more patients being offered reperfusion therapy. To address the inequalities in STEMI patients’ access to life-saving PPCI, and to support the implementation of the ESC STEMI treatment guidelines in Europe, the Stent for Life (SFL) Initiative was launched jointly by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and EuroPCR in 2008. National cardiac societies from Bulgaria, France, Greece, Serbia, Spain and Turkey signed the SFL Declaration at the ESC Congress in Barcelona in 2009. The aim of the SFL Initiative is to improve the delivery of, and STEMI patients’ access to, life-saving PPCI and thereby reduce mortality and morbidity. Currently, 10 national cardiac societies support the SFL Initiative in their respective countries. SFL national action programmes have been developed and are being implemented in several countries. The formation of regional PPCI networks involving emergency medical services, non-percutaneous coronary intervention hospitals and PPCI centres is considered to be a critical success factor in implementing PPCI services effectively. This article describes examples of how SFL countries are progressing in implementing their national programmes, thus increasing PPCI penetration in Europe.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Fu ◽  
C.X Song ◽  
X.D Li ◽  
Y.J Yang

Abstract Background The benefit of statins in secondary prevention of patients stabilized after acute coronary syndrome (ACS) has been well established. However, the benefit of preloading statins, i.e. high-intensity statins prior to reperfusion therapy remains unclear. Most previous studies included all types of ACS patients, and subgroup analysis indicated the benefit of preloading statins was only seen in ST-elevation myocardial infarction (STEMI) patients who underwent percutaneous coronary intervention (PCI). However, the sample size of subgroup population was relatively small and such benefit requires further validation. Objective To investigate the effect of loading dose of statins before primary reperfusion on 30-mortality in patients with STEMI. Methods We enrolled patients in China Acute Myocardial Infarction (CAMI) registry from January 2013 to September 2014. CAMI registry was a prospective multicenter registry of patients with acute acute myocardial infarction in China. Patients were divided into two groups according to statins usage: preloading group and control group. Patients in preloading group received loading does of statins before primary reperfusion and during hospitalization. Patients in control group did not receive statins during hospitalization or at discharge. Primary outcome was in-hospital mortality. Baseline characteristics, angiographic characteristics and outcome were compared between groups. Propensity score (PS) matching was used to mitigate baseline differences between groups and examine the association between preloading statins on in-hospital mortality risk. The following variables were used to establish PS matching score: age, sex, classification of hospitals, clinical presentation (heart failure at presentation, cardiac shock, cardiac arrest, Killip classification), hypertension, diabetes, prior angina, prior myocardial infarction history, prior stroke, initial treatment. Results A total of 1169 patients were enrolled in control group and 6795 in preloading group. A total of 833 patients (334 in control group and 499 in preloading group) died during hospitalization. Compared with control group, preloading group were younger, more likely to be male and present with Killip I classification. The proportion of hypertension and diabetes were higher in preloading group. After PS matching, all the variables used to generate PS score were well balanced. In the PS-matched cohort, 30-day mortality risk was 26.3% (292/1112) in the control group and 11.9% (132/1112) in the preloading group (p<0.0001). Conclusions The current study found preloading statins treatment prior to reperfusion therapy reduced in-hospital mortality risk in a large-scale contemporary cohort of patients with STEMI. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Chinese Academy of Medical Sciences


Sign in / Sign up

Export Citation Format

Share Document