Abstract 20478: Circulating Inflammatory Potential Measured by an Endothelial Biosensor Assay in Coronary Artery Disease Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Heidi Cung ◽  
Joe Anderson ◽  
James Nawarskas ◽  
Matthew Campen
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Adhesion Molecule ◽  
Inflammatory Markers ◽  
Serum Samples ◽  
Control Subjects ◽  
Tnf Α ◽  
Healthy Control ◽  
Artery Disease

Introduction: Vascular disease is driven by systemic inflammation that can arise from sites distal to the affected coronary or cerebral vessels. The objective of this study is to characterize the inflammatory potential of serum from patients with coronary artery disease (CAD) using cultured endothelial cells as a biosensor of the circulating milieu. Methods: Serum samples from CAD patients (N=48) and healthy control subjects (N=50) were incubated with primary human coronary artery endothelial cells at a 1:10 dilution for 4h, following by isolation of the cellular RNA. Alteration of inflammation-responsive elements (adhesion molecules and cytokines) was assessed on a gene expression level. Specific indicators included intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM), and interleukin-8 (IL-8). Additionally, the serum samples from the CAD patients and healthy individuals were quantitatively analyzed for IL-1β, IL-6, IL-8, and TNF-α using an electrochemical luminescence platform. Results: For the CAD subjects’ serum, the mean values of ICAM, VCAM, and IL-8 expression were all elevated compared to healthy control subjects (p<0.001 for each by Students T-test). Correlational analysis revealed the three indicators (ICAM, VCAM, and IL-8) to be independent of each other and also other inflammatory markers such as C-reactive protein. IL-8 expression was negatively correlated with serum HDL levels but positively correlated with body fat composition. Interestingly, serum levels of IL-1β, IL-6, IL-8, and TNF-α in CAD patients were not statistically different from healthy control subjects. Conclusions: As yet uncharacterized circulating factors in the serum of CAD patients appear to activate endothelial cells. This assay paradigm performed well in terms of discriminating patients with CAD compared to healthy subjects, with greater range and specificity than specific inflammatory markers.

scholarly journals IL-32 Serum Levels in Coronary Artery Disease Patient and its Relationship with IL-6 and TNF-α Serum Levels

2021 ◽  
Author(s):  
Mina Mohammad-Rezaei ◽  
Reza Ahmadi ◽  
Ali Rafiei ◽  
Arsalan Khaledifar ◽  
Shohila Fatahi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Serum Levels ◽  
Arterial Stenosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Subjects ◽  
Tnf Α ◽  
Significant Difference ◽  
Major Vessel ◽  
Artery Disease

Abstract Coronary Artery Disease (CAD) is a chronic inflammatory disease caused by atherosclerosis and arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a new proinflammatory cytokine, which enhances inflammation through inducing different inflammatory cytokines. The purpose of current research was to assess IL-32 serum levels in coronary artery disease subjects and its relationship with serum levels of IL-6 and TNF-α. Forty-two subjects diagnosed with CAD and thirty-nine control subjects were enrolled in the research. Serum levels of IL-6, TNF-α, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). IL-32, TNF-α, and IL-6 serum levels were significantly higher by 2.7, 3.48, and 3.2-fold in the CAD subjects than in control subjects, respectively. Moreover, no significant difference was found in TNF-α, IL-6 and IL-32 serum levels with the clogged arteries number in the CAD group. TNF-α and IL-32 serum levels in the CAD subjects with cardiac arterial stenosis in one major vessel were significantly increased than CAD subjects with cardiac arterial stenosis in more than one major vessels. ROC curve analysis revealed that serum levels of IL-32, TNF-α, and IL-6 showed good abilities in predicting CAD. Also, Multiple logistic regression analyses suggested that TNF-α, IL-6, and IL-32, serum levels of LDL and ox-LDL were independently related to the presence of CAD, while HDL serum levels were not. TNF-α, IL-32, and IL-6 showed an increase in CAD group and serum levels of these cytokines showed good abilities in predicting CAD. Our data suggested the involvement of TNF-α and IL-32 in the early stage of CAD.

Neopterin derivatives – a novel therapeutic target rather than biomarker for atherosclerosis and related diseases

VASA ◽  
2020 ◽  
pp. 1-9
Author(s):  
Takuya Watanabe
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Adhesion Molecule ◽  
Therapeutic Target ◽  
No Synthase ◽  
Foam Cell Formation ◽  
Atheromatous Plaques ◽  
Artery Disease ◽  
Novel Therapeutic

Summary: This review provides an updated overview of the emerging roles of neopterin derivatives in atherosclerosis. Neopterin, a metabolite of guanosine triphosphate, is produced by interferon-γ-activated macrophages and is expressed at high levels in atheromatous plaques within the human carotid and coronary arteries as well as in the aorta. Plasma concentrations of neopterin are higher in patients with carotid, cerebral, and coronary artery diseases as well as aortic aneurysm. The concentration of neopterin is positively correlated with the severity of coronary artery disease. However, a prospective cohort study showed that neopterin contributes to protection against plaque formation in carotid arteries in patients with atherosclerosis. Moreover, using both in vitro and in vivo experiments, a recent study has shown the atheroprotective effects of neopterin. Neopterin suppresses the expression of monocyte chemotactic protein-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in endothelial cells, and thereby suppresses the adhesion of monocytes to endothelial cells. It also suppresses the inflammatory phenotype of monocyte-derived macrophages. In addition, neopterin suppresses oxidized low-density lipoprotein-induced foam cell formation in macrophages and the migration and proliferation of vascular smooth muscle cells. Neopterin injection into apolipoprotein E-deficient ( Apoe-/-) mice suppresses the development of atherosclerotic lesions. A neopterin derivative tetrahydroneopterin (BH4), also known as a cofactor for nitric oxide (NO) synthases, suppresses atherosclerosis and vascular injury-induced neointimal hyperplasia in Apoe-/- mice. BH4 administration improves endothelial dysfunction in patients with coronary artery disease. These findings suggest that neopterin production may increase to counteract the progression of atherosclerosis, as neopterin contributes to atheroprotection. Otherwise, the increased neopterin levels in atherosclerosis may reflect a compensatory mechanism associated with inducible NO synthase upregulation in macrophages to supply BH4 for high output NO production caused by decreased endothelial NO synthase in atherosclerosis. Therefore, neopterin derivatives are a novel therapeutic target for atherosclerosis and related diseases.

scholarly journals Dietary flavanol intervention lowers the levels of endothelial microparticles in coronary artery disease patients

2013 ◽  
Vol 111 (7) ◽  
pp. 1245-1252 ◽  
Author(s):  
Patrick Horn ◽  
Nicolas Amabile ◽  
Franca S. Angeli ◽  
Roberto Sansone ◽  
Berthold Stegemann ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Current Evidence ◽  
Repair Capacity ◽  
Endothelial Microparticles ◽  
Control Subjects ◽  
Healthy Control ◽  
Artery Disease ◽  
Endothelial Integrity

Current evidence suggests that regenerative v. degenerative endothelial responses can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity. We have previously shown that a cocoa flavanol (CF) intervention can improve endothelial function and increase the regenerative capacity of the endothelium by mobilising circulating angiogenic cells in patients with coronary artery disease (CAD). The aim of the present study was to investigate whether CF can lower the levels of circulating endothelial microparticles (EMP), markers of endothelial integrity, along with improvements in endothelial function. The levels of EMP in the frozen plasma samples of CAD patients were measured along with endothelial function (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and these data were compared with those of young (n 12) and age-matched (n 12) healthy control subjects. The CAD patients exhibited significantly increased levels of EMP along with impaired FMD when compared with the healthy control subjects. The levels of CD144+ and CD31+/41− EMP were inversely correlated with FMD (r − 0·67, P= 0·01 and r − 0·59, P= 0·01, respectively). In these CAD patients, the levels of EMP were measured after they had consumed a drink containing 375 mg of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient-matched low-CF control, LoFl) twice daily over a 30-d period in a randomised, double-blind, cross-over study. After 1 month of HiFI, the levels of CD31+/41− and CD144+ EMP decreased ( − 25 and − 23 %, respectively), but not after LoFl. Our data show that flavanols lower the levels of EMP along with higher endothelial function, lending evidence to the novel concept that flavanols may improve endothelial integrity.

scholarly journals Effective microRNAs in Ischemia/Reperfusion Before and After Bypass Graft Surgery in Coronary Artery Patients

2020 ◽  
Author(s):  
Erman Kandilli ◽  
Şenay Görücü Yılmaz ◽  
Murat Yardımcı ◽  
Necla Benlier ◽  
Muradiye Nacak
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Bypass Graft ◽  
Characteristic Analysis ◽  
Serum Samples ◽  
Control Subjects ◽  
Before And After ◽  
Artery Disease

Abstract BackgroundCardiovascular diseases (CVD) are among the causes of morbidity and mortality in the world. Significant advances have been made in the diagnosis, treatment and prognosis of CVD. New biomarkers and therapeutic targets are needed to reduce the incidence of this disease. Recently, there is growing evidence that circulating microRNAs can be used as diagnostic biomarkers in this disease. Methods We compared five microRNA (hsa-miR-21-5p, hsa-mi181a-5p, hsa-miR-199a-5p, hsa-miR-199b-5p and hsa-miR-320a) expression levels associated with ischemia/reperfusion before and after bypass graft surgery in serum samples of patients (N=46) with coronary artery disease and healthy control subjects (N=48). Expression measurements were made for each miRNA preoperatively and postoperatively at 1. and 24. hours, and then compared with the control subjects. Troponin I, creatine phosphate kinase and creatine kinase myocardial band cardiac markers were measured before and 1 and 24 hours postoperatively and compared to miRNA expressions and controls. Quantitative real-time PCR was used for expression analysis. The data were analyzed by Mann-Whitney test, chi-squared test, Logistic Regression analysis, and Kruskal-Wallis test with the statistical package SPSS. Results The five miRNAs were down-regulated compared to controls. The expression level for miR-199a at 24 h postoperatively was significantly lower than at 1 h (p=0.001). Receiver operating characteristic analysis showed that the area under the curve of miR-199a-5p was 0.810 (sensitivity 87% and specificity 68.5%) in preoperative patients. Conclusions: miR-199a and miR-199b in serum are a novel non-invasive biomarker candidate for coronary artery disease.

Exercise training improves conduit vessel function in patients with coronary artery disease

2003 ◽  
Vol 95 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Jennifer H. Walsh ◽  
William Bilsborough ◽  
Andrew Maiorana ◽  
Matthew Best ◽  
Gerard J. O'Driscoll ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Exercise Training ◽  
Brachial Artery ◽  
Control Subjects ◽  
Vascular Ultrasonography ◽  
Healthy Control ◽  
Artery Disease ◽  
Routine Therapy ◽  
Conduit Vessel

It is well established that endothelial dysfunction is present in coronary artery disease (CAD), although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD. A randomized, crossover design determined the effect of 8 wk of predominantly lower limb, combined aerobic and resistance training, in 10 patients with treated CAD. Endothelium-dependent dilation of the brachial artery was determined, by using high-resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after ischemia. Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate (GTN). Baseline function was compared with that of 10 control subjects. Compared with matched healthy control subjects, FMD and GTN responses were significantly impaired in the untrained CAD patients [3.0 ± 0.8 (SE) vs. 5.8 ± 0.8% and 14.5 ± 1.9 vs. 20.4 ± 1.5%, respectively; both P < 0.05]. Training significantly improved FMD in the CAD patients (from 3.0 ± 0.8 to 5.7 ± 1.1%; P < 0.05) but not responsiveness to GTN (14.5 ± 1.9 vs. 12.1 ± 1.4%; P = not significant). Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD, and the effect, evident in the brachial artery, appears to be generalized rather than limited to vessels of exercising muscle beds. These results provide evidence for the benefit of exercise training, as an adjunct to routine therapy, in patients with a history of CAD.

scholarly journals Comparison of Arterial Stiffness Parameters in Patients With Coronary Artery Disease and Diabetes Mellitus Using Arteriograph

2014 ◽  
pp. 429-437
Author(s):  
Z. LENKEY ◽  
M. ILLYÉS ◽  
R. BÖCSKEI ◽  
R. HUSZNAI ◽  
Z. SÁRSZEGI ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Arterial Stiffness ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Pulse Wave ◽  
Control Subjects ◽  
Healthy Control ◽  
Artery Disease

Recently an expert consensus document advised to standardize user procedures and a new cut-off value for carotid-femoral pulse wave velocity in daily practice. Our aim was to observe aortic pulse wave velocity (PWVao) and augmentation index (AIXao) in two high cardiovascular risk groups: patients with verified coronary artery disease (CAD) or with type 2 diabetes mellitus (T2DM). We also aimed to determine the cut-off values for PWVao, AIXao in CAD and T2DM patients using oscillometric device (Arteriograph). We investigated 186 CAD and 152 T2DM patients. PWVao and AIXao increased significantly in the CAD group compared to the age-, gender-, blood pressure-, and heart rate-matched control group (10.2±2.3 vs. 9.3±1.5 m/s; p<0.001 and 34.9±14.6 vs. 31.9±12.8 %; p<0.05, respectively). When compared to the apparently healthy control subjects, T2DM patients had significantly elevated PWVao (9.7±1.7 vs. 9.3±1.5 m/s; p<0.05, respectively), however the AIXao did not differ significantly. The ROC-curves of CAD and healthy control subjects explored cut-off values of 10.2 m/s for PWVao and 33.23 % for AIXao. Our data provide supporting evidence about impaired arterial stiffness parameters in CAD and T2DM. Our findings encourage the implementation of arterial stiffness measurements by oscillometric method in daily clinical routine.

scholarly journals Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function

2003 ◽  
Vol 89 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Nicole Gottstein ◽  
Benjamin A. Ewins ◽  
Clair Eccleston ◽  
Gary P. Hubbard ◽  
Ian C. Kavanagh ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Platelet Aggregation ◽  
No Production ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tnf Α ◽  
Artery Disease

There has been much recent interest in the cardiovascular benefits of dietary isoflavones. The aim of the presentin vitrostudies was to investigate potential anti-thrombogenic and anti-atherogenic effects of the isoflavones genistein and daidzein in platelets, macrophages and endothelial cells. Pre-treatment with either isoflavone inhibited collagen-induced platelet aggregation in a dose-dependent manner. In a macrophage cell line (RAW 264·7) activated with interferon γ plus lipopolysaccharide, both isoflavones were found to inhibit NO production and tumour necrosis factor α (TNF-α) secretion dose-dependently, but they did not affect mRNA levels for inducible nitric oxide synthase and cyclo-oxygenase-2. Both isoflavones also dose-dependently decreased monocyte chemoattractant protein-1 secretion induced by TNF-α in human umbilical vein endothelial cells. Compared with daidzein, genistein exerted greater inhibitory effects for all parameters studied. The present data contributes to our knowledge on the molecular mechanisms by which isoflavones may protect against coronary artery disease. Further studies are required to determine whether the effects of isoflavones observed in the currentin vitrostudies are relevant to the aetiology of coronary artery diseasein vivo.

scholarly journals Detection of CirculatingChlamydophila pneumoniaein Patients with Coronary Artery Disease and Healthy Control Subjects

2009 ◽  
Vol 48 (5) ◽  
pp. 560-567 ◽  
Author(s):  
Sarah Klizas West ◽  
Sue J. Kohlhepp ◽  
Ruyun Jin ◽  
Curt A. Gleaves ◽  
Walter Stamm ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Control Subjects ◽  
Healthy Control ◽  
Artery Disease
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