scholarly journals Epithelial-Mesenchymal Transition-Related lncRNAs And SNAI2 Are Potential Biomarkers in Coronary Artery Disease

Author(s):  
Xiang Xu ◽  
Renchao Zou ◽  
Xiaoyong Liu ◽  
Qianqian Su

Abstract BackgroundIncreasing evidence suggests that epithelial-mesenchymal transformation (EMT) is critical in the development of inflammatory response, atherosclerosis, and coronary artery disease (CAD). However, landscapes of EMT-related lncRNAs and their target genes have not been fully established in CAD.MethodsLncRNA and mRNA expression profiles obtained from Gene Expression Omnibus (GEO) database were used to identify the differentially expressed mRNAs (DEGs) and lncRNAs (DElncRNAs) between CAD and normal samples. Based on Pearson correlation analysis to identify the EMT-related lncRNAs, the optimal features were identified by receiver operating characteristic (ROC), the least absolute shrinkage and selection operator (LASSO) regression, Support Vector Machine Reverse Feature Elimination (SVM-RFE) algorithms, and logistic regression models were constructed aiming to distinguish CAD from normal samples. The cis and trans-regulatory networks were constructed based on EMT-related lncRNAs. We further estimated the infiltration of the immune cells in CAD patients with the CIBERSORT algorithm, and the correlation between key genes and infiltrating immune cells was analyzed.ResultsIn this study, a logistic regression model with powerful diagnostic capability was constructed based on a total of eight EMT-related lncRNAs identified by two machine learning methods. Then, results of the immune analysis revealed three significant immune cell subsets (CD8 T cells, monocytes, and NK cells) in CAD patients and found EMT-related lncRNAs were closely correlated with these immune cell subsets. By Pearson correlation analysis we got 34 “cis” and “trans” genes. Among them, SNAI2, an EMT-TF gene, was found in the trans-regulatory network of EMT-related lncRNAs. Further, through logistic regression and analysis of immune cell infiltration, we found SNAI2 was a potential biomarker for the diagnosis of CAD but also a close correlation between highly expressed SNAI2 and these three immune cell subsets in CAD patients.ConclusionIn conclusion, these biomarkers have important significance in the diagnosis of CAD patients. Eight EMT-related lncRNAs and SNAI2 can improve our understanding of the molecular mechanism between EMT and CAD.

2021 ◽  
Author(s):  
Xiang Xu ◽  
Renchao Zou ◽  
Xiaoyong Liu ◽  
Qianqian Su

Abstract BackgroundIncreasing evidence suggests that epithelial-mesenchymal transformation (EMT) is critical in the development of inflammatory response, atherosclerosis, and coronary artery disease (CAD). However, landscapes of EMT-related lncRNAs and their target genes have not been fully established in CAD.MethodsLncRNA and mRNA expression profiles obtained from Gene Expression Omnibus (GEO) database were used to identify the differentially expressed mRNAs (DEGs) and lncRNAs (DElncRNAs) between CAD and normal samples. Based on Pearson correlation analysis to identify the EMT-related lncRNAs, the optimal features were identified by receiver operating characteristic (ROC), the least absolute shrinkage and selection operator (LASSO) regression, Support Vector Machine Reverse Feature Elimination (SVM-RFE) algorithms, and logistic regression models were constructed aiming to distinguish CAD from normal samples. The cis and trans-regulatory networks were constructed based on EMT-related lncRNAs. We further estimated the infiltration of the immune cells in CAD patients with the CIBERSORT algorithm, and the correlation between key genes and infiltrating immune cells was analyzed.ResultsIn this study, a logistic regression model with powerful diagnostic capability was constructed based on a total of eight EMT-related lncRNAs identified by two machine learning methods. Then, results of the immune analysis revealed three significant immune cell subsets (CD8 T cells, monocytes, and NK cells) in CAD patients and found EMT-related lncRNAs were closely correlated with these immune cell subsets. By Pearson correlation analysis we got 34 “cis” and “trans” genes. Among them, SNAI2, an EMT-TF gene, was found in the trans-regulatory network of EMT-related lncRNAs. Further, through logistic regression and analysis of immune cell infiltration, we found SNAI2 was a potential biomarker for the diagnosis of CAD but also a close correlation between highly expressed SNAI2 and these three immune cell subsets in CAD patients.ConclusionIn conclusion, these biomarkers have important significance in the diagnosis of CAD patients. Eight EMT-related lncRNAs and SNAI2 can improve our understanding of the molecular mechanism between EMT and CAD.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Marlies P Noz ◽  
Siroon Bekkering ◽  
Laszlo Groh ◽  
Tim MJ Nielen ◽  
Evert JP Lamfers ◽  
...  

Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after ex vivo stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.


Author(s):  
Eka Prasetya Budi Mulia ◽  
Kevin Yuwono ◽  
Raden Mohammad Budiarto

Abstract Objectives We aimed to investigate the association between hypertension and asymptomatic lower extremity artery disease (LEAD) in outpatients with known history of coronary artery disease (CAD). Methods Patients with known history of CAD who have been undergone coronary angiography and have significant coronary artery stenosis (more than 60%) were included. LEAD was defined as ankle-brachial index (ABI) < 0.9 in either leg. The risk of LEAD in hypertensive group was analyzed using chi-square test, and correlation between blood pressure (BP) and ABI was analyzed using Pearson correlation test in SPSS v.25. Results One hundred and four patients were included. 82.7% of patients were male. Mean age was 57.05 ± 7.97. The prevalence of hypertension was 35.6%, and the prevalence of LEAD was 16.3%. A higher proportion of LEAD was found in hypertensive (18.9%) compared to non-hypertensive (14.9%), although not statistically significant (OR: 1.33; 95% CI: 0.46 to 3.85; p=0.598). There was an association between ABI and systolic BP (p=0.016), but not with diastolic BP (p=0.102). Conclusions Our study showed that the prevalence of LEAD in hypertension, especially in the CAD population, is relatively high. There was no association between hypertension and LEAD, but a higher prevalence of LEAD was found in hypertensive patients. Nevertheless, LEAD screening is still recommended in hypertensive patients, especially in the CAD population, given the fact that outcomes of health and mortality are worse for those with concomitants of these diseases.


2019 ◽  
Vol 95 (1120) ◽  
pp. 67-71 ◽  
Author(s):  
Lishan Chen ◽  
Hang Qian ◽  
Zhihuan Luo ◽  
Dongfeng Li ◽  
Hao Xu ◽  
...  

BackgroundCoronary artery disease (CAD) is the most frequent multifactorial disease worldwide and is characterised by endothelial injury, lipid deposition and coronary artery calcification. The purpose of this study was to determine the allelic and genotypic frequencies of two loci (rs2026458 and rs9349379) of phosphatase and actin regulator 1 (PHACTR1) to the risk of developing CAD in the Chinese Han population.MethodsA case–control study was conducted including 332 patients with CAD and 119 controls. Genotype analysis was performed by PCR and Sanger sequencing. Genetic model analysis was performed to evaluate the association between single nucleotide polymorphisms and CAD susceptibility using Pearson’s χ2 test and logistic regression analysis.ResultsThe GG genotype of rs9349379 represented 50% and 29% of patients with CAD and controls, respectively (p<0.001). The CC genotype of rs2026458 was more prevalent in the controls than in patients with CAD compared with TT genotype (OR=0.548, 95% CI 0.351 to 0.856, p=0.008). Logistic regression analyses revealed that PHACTR1 rs9349379 GG genotype was significantly associated with increased risk of CAD in the recessive model (OR=2.359, 95% CI 1.442 to 3.862, p=0.001), even after adjusting for age gender, hypertension, type 2 diabetes, hyperlipidaemia and smoking habit. Heterogeneity test proved that rs9349379’s risk effects on CAD were more significant among women.ConclusionsOur study indicate that the PHACTR1 rs9349379 polymorphism is associated with the increased risk for CAD in the female Chinese Han population.


2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Katharine A. Kott ◽  
Stephen T. Vernon ◽  
Thomas Hansen ◽  
Macha de Dreu ◽  
Souvik K. Das ◽  
...  

Abstract Coronary artery disease remains the leading cause of death globally and is a major burden to every health system in the world. There have been significant improvements in risk modification, treatments, and mortality; however, our ability to detect asymptomatic disease for early intervention remains limited. Recent discoveries regarding the inflammatory nature of atherosclerosis have prompted investigation into new methods of diagnosis and treatment of coronary artery disease. This article reviews some of the highlights of the important developments in cardioimmunology and summarizes the clinical evidence linking the immune system and atherosclerosis. It provides an overview of the major serological biomarkers that have been associated with atherosclerosis, noting the limitations of these markers attributable to low specificity, and then contrasts these serological markers with the circulating immune cell subtypes that have been found to be altered in coronary artery disease. This review then outlines the technique of mass cytometry and its ability to provide high‐dimensional single‐cell data and explores how this high‐resolution quantification of specific immune cell subpopulations may assist in the diagnosis of early atherosclerosis in combination with other complimentary techniques such as single‐cell RNA sequencing. We propose that this improved specificity has the potential to transform the detection of coronary artery disease in its early phases, facilitating targeted preventative approaches in the precision medicine era.


Angiology ◽  
2020 ◽  
pp. 000331972095998
Author(s):  
Bülent Deveci ◽  
Emine Gazi

The albumin to globulin ratio (AGR) is used as a prognostic marker in acute ischemic cardiovascular events. We investigated whether serum AGR, fibrinogen, and fibrinogen to albumin ratio (FAR) are related to the presence and severity of coronary artery disease (CAD). Patients who underwent coronary angiography procedures were analyzed retrospectively. The severity of CAD was assessed by the Gensini score. The study population (3031 patients; 1071 females and 1960 males) was divided into 3 tertiles based on AGR values. Gensini score, lipid levels, diabetes mellitus (DM), hypertension (HT), age, and fibrinogen level were higher in the low AGR group. Pearson correlation analysis showed that AGR ( r = −0.068, P < .001) was negatively and fibrinogen ( r = 0.187, P < .001) was positively correlated with the Gensini score. Male gender, HT, smoking, DM, age, high triglyceride (TG) level, low-density lipoprotein cholesterol (LDL-C) >160 mg/dL, estimated glomerular filtration rate (eGFR) <60 mL/min, and fibrinogen level >3.5 g/L were independent predictors of CAD. Male gender, age, eGFR, DM, LDL-C, TG, and FAR had an independent positive relation to the Gensini score. In conclusion, similar to traditional risk factors, plasma fibrinogen and albumin levels showed a close relation with the presence and severity of CAD.


2003 ◽  
Vol 90 (08) ◽  
pp. 344-350 ◽  
Author(s):  
Alexander Niessner ◽  
Senta Graf ◽  
Mariam Nikfardjam ◽  
Walter Speidl ◽  
Renate Huber-Beckmann ◽  
...  

SummaryThrombus formation after rupture of an atherosclerotic plaque plays a crucial role in coronary artery disease (CAD). A decreased endogenous fibrinolytic system and prothrombotic factors are supposed to influence coronary thrombosis. It was our aim to investigate the predictive value of tissue plasmino-gen activator (t-PA) antigen, von Willebrand Factor, Lipoprotein (a) and anti-cardiolipin antibodies for major adverse coronary events in patients with stable CAD in a prospective cohort study of more than 10 years.We observed 141 patients with angiographically proven CAD for a median follow-up period of 13 years. t-PA antigen was the only marker predicting coronary events (logistic regression, p = 0.044) with a poor prognosis for patients in the 5th quintile with an odds ratio of 7.3 (compared to the 1st quintile). The odds ratio even increased to 10.0 for coronary events associated with the “natural course” of CAD excluding events due to restenosis. t-PA antigen had a slightly higher prognostic power (ROC curve; AUC = 0.69) than fasting glucose (AUC = 0.68) and cholesterol (AUC = 0.67). Triglycerides influenced plasma levels of t-PA antigen (regression, p < 0.001). The predictive value of t-PA antigen remained significant after adjustment for inflammation (logistic regression, p = 0.013) and extent of CAD (p = 0.045) but disappeared adjusting for insulin resistance (p = 0.12).In conclusion t-PA antigen predicted coronary events during a very long-term follow-up with a comparable prognostic power to established cardiovascular risk factors. Markers of insulin resistance influenced t-PA antigen and its predictive value.Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September 2002.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Nan-Han Lu ◽  
Lee-Ren Yeh ◽  
Tai-Been Chen ◽  
Yung-Hui Huang ◽  
Chung-Ming Kuo ◽  
...  

Purpose. Coronary artery calcification (CAC) scores are widely used to determine risk for Coronary Artery Disease (CAD). A CAC score does not have the diagnostic accuracy needed for CAD. This work uses a novel efficient approach to predict CAD in patients with low CAC scores.Materials and Methods. The study group comprised 86 subjects who underwent a screening health examination, including laboratory testing, CAC scanning, and cardiac angiography by 64-slice multidetector computed tomographic angiography. Eleven physiological variables and three personal parameters were investigated in proposed model. Logistic regression was applied to assess the sensitivity, specificity, and accuracy of when using individual variables and CAC score. Meta-analysis combined physiological and personal parameters by logistic regression.Results. The diagnostic sensitivity of the CAC score was 14.3% when the CAC score was ≤30. Sensitivity increased to 57.13% using the proposed model. The statistically significant variables, based on beta values andPvalues, were family history, LDL-c, blood pressure, HDL-c, age, triglyceride, and cholesterol.Conclusions. The CAC score has low negative predictive value for CAD. This work applied a novel prediction method that uses patient information, including physiological and society parameters. The proposed method increases the accuracy of CAC score for predicting CAD.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ho Gi Jung ◽  
Ya Ki Yang

Abstract Background The purpose of this study was to investigate the relationships among cardiac rehabilitation knowledge, educational need and health behavior practice in patients with coronary artery disease and explain factors influencing health behavior practice. Method The research participants were 189 patients with coronary artery disease from general hospital located in Korea. Self-evaluation questionnaires were used to collect the data. Data was collected from January to May, 2020. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficients and multiple regression with the SPSS 24.0 program. Results There were significant positive relationships between cardiac rehabilitation knowledge and health behavior practice (r = .37, p < .001), and significant positive relationships between educational need and health behavior practice (r = .17, p = .022). Factors influencing health behavior practice were identified, the most critical predictive factor was age (≥80) (β = .52), followed by cardiac rehabilitation knowledge (β = .42), regular exercise (No) (β = −.25), family history (No) (β = .24), age (60-69) (β = .22), cohabitation (No) (β = −.20) and educational needs (β = .17). The explanation power of this model was 50% and it was statistically significant (F = 13.42, p < .001). Conclusion This study suggests that cardiac rehabilitation knowledge and educational need should be considered in enhancing cardiac rehabilitation programs designed for patients with coronary artery disease.


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