Blood Of Coronary Artery Disease Patients Research Articles

Gene Expression Changes in CAD Patients Due to Smoking Using Matched Samples

Abstract Background Smoking is a well-known risk factor for coronary artery disease (CAD). However, the effects of smoking on gene expression in the blood of CAD patients in Hungary have not been extensively studied. Aim To identify differentially expressed genes associated with smoking in CAD patients. Methods Eleven matched samples, based on age and gender, were selected for analysis in this study. All patients were non-obese, non-alcoholic, non-diabetic, and non-hypertensive and had moderate to severe stenosis of one or more coronary arteries, confirmed by coronary angiography. Whole blood samples were collected using PAXgene tubes. Next-generation sequencing was employed using the NextSeq 500 system to generate high-throughput sequencing data for transcriptome profiling. The differentially expressed genes were analyzed using the R programming language. Results The median age of patients was 67 years (range: 54-75). RNA sequencing was performed on two groups: smokers and non-smokers. After quality control and filtering, gene expression data were obtained for all samples. Using DESeq2, we identified 279 differentially expressed genes with a p-value ≤ 0.05 and a log2 fold change ≥1. Of these genes, 160 were upregulated in the smokers, and 119 were downregulated compared to non-smokers. Gene ontology analysis revealed that the upregulated genes were enriched for pathways related to immune responses and activities (FDR< 0.03). Specifically, upregulated genes were involved in keratinocyte differentiation, cornification, and epidermis development. The downregulated genes were enriched for cell-cardiac muscle cell adhesion (FDR= 0.004) and epithelium development (FDR= 0.001) pathways. Conclusions This research illuminates smoking’s biological effects, aiding personalized medicine for predicting and treating smoking-related diseases. Key messages • Smoking alters gene expression in CAD patients’ blood, identifying 279 differentially expressed genes, revealing smoking’s biological effects. • The study underscores gene expression profiles’ role in personalized medicine, predicting smoking-related disease risks and tailoring CAD patient treatments.

Differentiation and subpopulation composition of VEGFR2+ cells in the blood and bone marrow in ischemic cardiomyopathy

Aim. To identify disturbances of differentiation and subpopulation composition of VEGFR2+ cells in the blood and bone marrow associated with the features of the cytokine profile in the blood and bone marrow in patients with coronary artery disease (CAD) with and without ischemic cardiomyopathy (ICM).Materials and methods. The study included 74 patients with СAD with and without ICM (30 and 44 people, respectively) and 18 healthy donors. In all patients with СAD, peripheral blood sampling was performed immediately before coronary artery bypass grafting, and bone marrow samples were taken during the surgery via a sternal incision. In the healthy donors, only peripheral blood sampling was performed. In the bone marrow and blood samples, the number of VEGFR2+ cells (CD14+VEGFR2+ cells) and their immunophenotypes CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+, CD14+CD16++VEGFR2+, and CD14+CD16-VEGFR2+ was determined by flow cytometry. Using enzyme-linked immunosorbent assay, the levels of VЕGF-А, TNFα, M-CSF, and IL-13, as well as the content of MCP-1 (only in the blood) and the M-CSF / IL-13 ratio (only in the bone marrow) were determined.Results. The content of CD14+VEGFR2+ cells in the blood of CAD patients with and without ICM was higher than normal values due to the greater number of CD14++CD16-VEGFR2+, CD14++CD16+VEGFR2+, and CD14+CD16++VEGFR2+. In the bone marrow of the patients with ICM, the content of CD14++CD16-VEGFR2+, CD14+CD16++VEGFR2+, and CD14+CD16-VEGFR2+ was lower than in patients with CAD without ICM, and the number of CD14++CD16+VEGFR2+ cells corresponded to that in the controls. Regardless of the presence of ICM in CAD, a high concentration of TNFα and normal levels of VEGF-A and IL-13 were observed in the blood. In CAD without ICM, an excess of MCP-1 and deficiency of M-CSF were revealed in the blood. In the bone marrow, the levels of VEGF-A, TNFα, M-CSF, and IL-13 were comparable between the groups of patients against the background of a decrease in the M-CSF / IL-13 ratio in the patients with ICM.Conclusion. Unlike CAD without cardiomyopathy, in ICM, no excess of VEGFR2+ cells and MCP-1 in the blood is observed, which hinders active migration of CD14+CD16++VEGFR2+ cells from the myeloid tissue, and a decrease in the M-CSF / IL-13 ratio in the bone marrow disrupts differentiation of other forms of VEGFR2+ cells, preventing vascular repair.

Expression analysis of inflammatory response-associated genes in coronary artery disease

Background Coronary artery disease (CAD) is among prominent causes of death throughout the world. Inflammatory processes participate in the pathogenesis of this disorder. Methods In the current case–control study, we compared expression levels of three inflammation-associated genes namely Antisense noncoding RNA in the INK4 locus (ANRIL), NKILA and IL-1B between CAD patients and matched healthy subjects. Results ANRIL, IL-1B and NKILA were significantly down-regulated in CAD patients compared with controls (p values of <.0001, .023 and <.0001, respectively). When evaluating study participants based on their gender, the differences in expression levels of ANRIL and NKILA were significant in both male and female patients compared with the matched controls. However, IL-1B was only down-regulated in female patients compared with female controls. Conclusion Taken together, our study revealed dysregulation of inflammation-associated genes in the peripheral blood of CAD patients and supported the previously suggested role of inflammation in the pathogenesis of CAD.

Association of Increased Levels of lncRNA H19 in PBMCs with Risk of Coronary Artery Disease.

Objective Considerable research shows that long non-coding RNAs, those longer than 200 nucleotides, are involved in several human diseases such as various cancers and cardiovascular diseases. Their significant role in regulating the function of endothelial cells, smooth muscle cells, macrophages, vascular inflammation, and metabolism indicates the possible effects of lncRNAs on the progression of atherosclerosis which is the most common underlying pathological process responsible for coronary artery disease (CAD). The aim of present study was to assess whether the expression of the lnc RNA H19 was associated with a susceptibility to CAD by evaluating the expression level of H19 in the peripheral blood. Materials and Methods A case-control study of 50 CAD patients and 50 age and sex-matched healthy controls was undertaken to investigate whether the H19 lncRNA expression level is associated with a CAD using Taqman Real-Time polymerase chain reaction (PCR). Results The subsequent result indicated that the H19 lncRNA was over-expressed in CAD patients in comparison with the controls. However, it was not statistically significant. This overexpression may be involved in coronary artery disease progression. ConclusionWe report here, the up-regulation of H19 lncRNA in the whole blood of CAD patients and suggest a possible role for H19 in the atherosclerosis process and its consideration as novel biomarker for CAD.

MicroRNA-93 elevation after myocardial infarction is cardiac protective

Coronary Artery Disease (CAD) is one of the most serious diseases that endangers human health worldwide, myocardial infarction (MI) is an acute form of CAD. Recent developments in MI therapies have resulted in significant reductions in mortality. However, subsequent chronic congestive heart failure and ventricle remodeling plagues an increasing number of MI patients. MicroRNAs (miR) have been reported to be involved in the process of cardiac remodeling, a recent study shows that miR-93 is elevated in the blood of CAD patients. Similar to human CAD, we found miR-93 is elevated both in ventricle tissue and blood in mice MI model, and miR-93 is secreted from cardiomyocytes cultured under hypoxia. Interestingly, miR-93 inhibits apoptosis and protects cardiomyocytes from ischemia/reperfusion injury. In other type of ischemic disease like stoke and peripheral arterial disease, miR-93 shows long term protective effects via enhancing angiogenesis, inducing macrophage M2 polarization and antioxidant effects. These effects are favorable for ventricle remodeling inhibition after MI. In a pilot experiment, we indicated that miR-93 knockdown deteriorate cardiac remodeling in 30days after MI in mice models. Therefore, we hypothesize that miR-93 upregulation and secretion from cardiomyocytes after MI is adaptive, which could inhibit cardiac remodeling and heart failure.

Higher incidence of persistent chronic infection of Chlamydia pneumoniae among coronary artery disease patients in India is a cause of concern

BackgroundThere is growing evidence that Chlamydia pneumoniae may be involved in the pathogenesis of atherosclerosis, as several studies have demonstrated the presence of the organism in atherosclerotic lesions. C. pneumoniae infections, which are especially persistent infections, have been difficult to diagnose either by serological methods or isolation of the organism from the tissue. Nucleic Acid Amplification tests (NAATs) has emerged as an important method for detecting C. pneumoniae. Inspite of high prevalence of C. pneumoniae specific antibodies in coronary heart disease patients, direct detection of C. pneumoniae in circulating blood of coronary artery disease (CAD) patients by sensitive nucleic acid amplification tests nested PCR (nPCR), multiplex PCR (mPCR) has not been carried out is required. Further correlation of the presence of C. pneumoniae in blood of CAD patients with C. pneumoniae specific IgA and IgG antibodies, which may indicative of the status of infection with the progression of atherosclerosis. This will help in order to prepare strategies for the antibiotic intervention to avoid the progression towards CAD.MethodsVenous blood was obtained from 91 CAD patients and 46 healthy controls. Nucleic acid amplification tests viz. nested -, semi-nested – and multiplex PCR were used for detection of C. pneumoniae. ELISA carried out prevalence of C. pneumoniae specific IgG and IgA antibodies.Results29.67% (27/91) patients were positive for C. pneumoniae using nested PCR. The sensitivity and specificity of semi-nested and multiplex PCR were 37.03%, 96.96% and 22.22%, 100% with respect to nested PCR. Positive nPCR patients were compared with presence of C. pneumoniae specific IgA, IgA+IgG and IgG antibodies. Among 27 (29.67%) nPCR C. pneumoniae positive CAD patients, 11(12%) were IgA positive, 13(14.2%) were IgA+IgG positive and only1 (1.1%) was IgG positive. A significant presence of C. pneumoniae was detected in heavy smokers, non-alcoholics and with family histories of diabetes and blood pressure group of CAD patients by nPCR.ConclusionThe results indicate synergistic association of C. pneumoniae infection and development of CAD with other risk factors. We also detected increased positivity for C. pneumoniae IgA than IgG in nPCR positive CAD patients. Positive nPCR findings in conjunction with persisting high C. pneumoniae specific antibody strongly suggest an ongoing infection.

Therapeutic effect of diagnostic ultrasound on enzymatic thrombolysis. An in vitro study on blood of normal subjects and patients with coronary artery disease.

If delivered at elevated intensity, ultrasound potentiates enzymatic clot dissolution; however, an elevated acoustic intensity damages vascular wall and favors reocclusion. This study's aim was to investigate whether exposure to high-frequency, low-intensity ultrasound - generated by a diagnostic scanner -enhances enzymatic thrombolysis, and if this effect differs in clots from blood of normal subjects and of patients with coronary artery disease (CAD). Venous blood samples were drawn from 10 healthy volunteers and from 10 CAD patients on chronic medical treatment, which also included aspirin. Each sample generated 2 radiolabelled clots, which were positioned in 2 in vitro models filled with human plasma recirculating at 37 degrees. One clot was exposed to acetyl salicylic acid (60 microg/ml), tissue plasminogen activator (3 microg/ml) and heparin (1 IU/ml), while the other was exposed to the same medications plus ultra-sound (2.5 MHz, mechanical index = 1.0) for 3 hours. Enzymatic thrombolysis was measured as solubilization of radiolabel. Normal subjects and patients did not significantly differ as to coagulation parameters, weight, volume and density of the clots, and fibrinolytic activity (p = 0.794). Ultrasound exposure did not influence thrombolysis in clots of normal subjects (p = 0.367), while it enhanced the dissolution of clots of CAD patients (p = 0.013). The enhancement was equal to 51% at 5 minutes, 32% at 15 minutes, 27% at 30 minutes, 20% at 1 hour and 19% at 3 hours (p < 0.05). Diagnostic ultrasound enhances enzymatic dissolution of clots generated from the blood of CAD patients, likely due to chronic treatment and in particular to aspirin.