scholarly journals A Novel Method of Immunomodulation of Endothelial cells Using Streptococcus Pyogenes and its Lysate

2020 ◽  
Author(s):  
Mark Christopher Arokiaraj ◽  
Jarad Wilson
Keyword(s):  
Cell Culture ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Streptococcus Pyogenes ◽  
Immune Modulation ◽  
Principal Component ◽  
Second Phase ◽  
Novel Method ◽  
Artery Disease ◽  
Pleiotropic Functions

AbstractBackgroundCoronary artery diseases and autoimmune disorders are common in clinical practice. In this study, a novel method of immune-modulation to modify the endothelial function was studied to modulate the features of the endothelial cells, and thereby to reduce coronary artery disease and other disorders modulated by endothelium.MethodsHUVEC cells were seeded in the cell culture, and streptococcus pyogenes were added to the cell culture, and the supernatant was studied for the secreted proteins. In the second phase, the bacterial lysate was synthesized, and the lysate was added to cell culture; and the proteins in the supernatant were studied at various time intervals.ResultsWhen streptococcus pyogenes alone was added to culture, E Cadherin, Angiostatin, EpCAM and PDGF-AB were some of the biomarkers elevated significantly. HCC1, IGFBP2 and TIMP were some of the biomarkers which showed a reduction. When the lysate was added, the cell-culture was maintained for a longer time, and it showed the synthesis of immune regulatory cytokines. Heatmap analysis showed a significant number of proteins/cytokines concerning the immune/pathways, and toll-like receptors superfamily were modified. BLC, IL 17, BMP 7, PARC, Contactin2, IL 10 Rb, NAP 2 (CXCL 7), Eotaxin 2 were maximally increased. By principal component analysis, the results observed were significant.ConclusionThere is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using streptococcus pyogenes and its lysates.

scholarly journals A novel method of immunomodulation of endothelial cells using Streptococcus pyogenes and its lysate

2021 ◽  
Vol 19 (2) ◽  
pp. 116-128
Author(s):  
Mark Christopher Arokiaraj ◽  
◽  
Jarad Wilson ◽  
Keyword(s):  
Cell Culture ◽  
Endothelial Cells ◽  
Streptococcus Pyogenes ◽  
Principal Component ◽  
Second Phase ◽  
Coronary Artery Diseases ◽  
Bacterial Lysate ◽  
Novel Method ◽  
Huvec Cells ◽  
Pleiotropic Functions

Introduction. Coronary artery diseases and autoimmune disorders are common in clinical practice. Aim. In this study, Streptococcus pyogenes and its lysate were studied to modify the endothelial function. Material and methods. HUVEC cells were seeded in the cell culture, and Streptococcus pyogenes were added to the cell culture, and the supernatant was studied for the secreted proteins. In the second phase, the bacterial lysate was synthesized, and the lysate was added to cell culture and studied. Results. When S. pyogenes alone was added to culture, E Cadherin, Angiostatin, EpCAM and PDGF-AB were some of the biomarkers elevated significantly. HCC1, IGFBP2 and TIMP were some of the biomarkers which showed a reduction. When the lysate was added, the cell-culture was maintained for a longer time, and it showed the synthesis of immune regulatory cytokines. Heatmap analysis showed a significant number of proteins/cytokines concerning the immune/pathways, and toll-like receptors superfamily were modified. BLC, IL 17, BMP 7, PARC, Contactin2, IL 10 Rb, NAP 2 (CXCL 7), Eotaxin 2 were maximally increased. By principal component analysis, the results observed were significant. Conclusion. There is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using S. pyogenes and its lysates.

Identification of Coronary Artery Disease using Artificial Neural Network and Case Based Reasoning

2020 ◽  
Vol 13 ◽  
Author(s):  
Varun Sapra ◽  
M.L Saini ◽  
Luxmi Verma
Keyword(s):  
Neural Network ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Early Stage ◽  
Second Phase ◽  
Case Based Reasoning ◽  
Data Set ◽  
Artery Disease ◽  
Severity Of The Disease ◽  
Case Based

Background: Cardiovascular diseases are increasing at an alarming rate with very high rate of mortality. Coronary artery disease is one of the type of cardiovascular disease, which is not easily diagnosed in its early stage. Prevention of Coronary Artery Disease is possible only if it is diagnosed, at early stage and proper medication is done. Objective: An effective diagnosis model is important not only for the early diagnosis but also to check the severity of the disease. Method: In this paper, a hybrid approach is followed, with the integration of deep learning (multi-layer perceptron) with Case based reasoning to design analytical framework. This paper suggests two phases of the study, one in which the patient is diagnosed for Coronary artery disease and in second phase, if the patient is suffering from the disease then employing Case based reasoning to diagnose the severity of the disease. In the first phase, multilayer perceptron is implemented on reduced dataset and with time-based learning for stochastic gradient descent respectively. Results: The classification accuracy is increase by 4.18 % with reduced data set using deep neural network with time based learning. In second phase, if the patient is diagnosed as positive for Coronary artery disease, then it triggers the Case based reasoning system to retrieve from the case base, the most similar case to predict the severity for that patient. The CBR model achieved 97.3% accuracy. Conclusion: The model can be very useful for medical practitioners as a supporting decision system and thus can save the patients from unnecessary medical expenses on costly tests and can improve the quality and effectiveness of medical treatment.

Abstract 414: In Hyperalphalipoproteinemic Subjects, the Presence of Coronary Artery Disease is Associated With Marked Changes in the High-Density Lipoprotein Phosphosphingolipidome

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
William Hancock-Cerutti ◽  
Marie Lhomme ◽  
Carolane Dauteuille ◽  
Sora Lecocq ◽  
John Chapman ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chemical Composition ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Edta Plasma ◽  
Novel Method ◽  
Artery Disease ◽  
Causal Nature ◽  
A Minor

Plasma concentrations of HDL-C have long been shown to correlate inversely with risk of coronary artery disease (CAD), however the causal nature of this association has not been established. Here we examine the chemical composition and phosphoshingolipidome of HDL in a cohort of subjects with premature CAD, despite having HDL levels ≥90th percentile. We hypothesized that HDL from hyperalphalipoproteinemic subjects with CAD would have distinct compositional changes compared to healthy hyperalphalipoproteinemic subjects, which may relate a reduction in HDL functionality and a pro-atherogenic state. Subjects with HDL ≥90th percentile and CAD (HHDL+CAD, n=25) were compared to healthy subjects with HDL ≥90th percentile (HHDL, n=23). A group of healthy controls with HDL between the 25th and 75th percentile (n=11) was used as reference. HDL subfractions were isolated from EDTA plasma using isopycnic density gradient ultracentrifugation and their chemical composition was assayed using commercial enzymatic assay kits. Quantification of >160 molecular species of total HDL phospho- and sphingolipids was accomplished via a novel method using LC-ESI/MS/MS analysis. The most striking differences were observed in total HDL phospho- and sphingolipid subclasses between groups. When expressed as a percentage of total phosphosphingolipid, phosphatidylcholine (PC) and phosphatidylinositol (PI) were depleted in HHDL+CAD group compared to HHDL, while sphingomyelin (SM) was increased, resulting in a lower PC/SM ratio. The HDL PC/SM ratio has previously been shown to correlate with HDL surface fluidity and antioxidative activity. Additionally, enrichment of PI, a minor, negatively charged phospholipid, has been shown to stimulate cholesterol efflux to reconstituted HDL. Reduction in these two metrics, observed in the HHDL+CAD group, may indicate functionally deficient HDL and may represent pro-atherogenic, HDL-associated biomarkers of CAD in hyperalphalipoproteinemia.

Abstract 426: Overexpression of Tissue-nonspecific Alkaline Phosphatase (TNAP) Accelerates Coronary Artery Disease in the Setting of Hypercholesterolemia in Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Filippo Romanelli ◽  
AnthonyMarco Corbo ◽  
Maryam Salehi ◽  
Manisha C Yadav ◽  
Soha Salman ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Alkaline Phosphatase ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Vascular Calcification ◽  
Coronary Atherosclerosis ◽  
Atherogenic Diet ◽  
Arterial Calcification ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
Artery Disease

Objective: Vascular calcification in asymptomatic individuals is an independent predictor of coronary heart disease (CHD). It is therefore plausible that vascular calcification plays a direct pathophysiological role in atherosclerosis, an underlying cause of CHD. The purpose of this study was to examine the contribution that vascular calcification has on the development of coronary atherosclerosis in a mouse model of familial hypercholesterolemia. Approach and Results: Calcification was induced by overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells of mice harboring a point mutation in the low density lipoprotein receptor ( ldlr, wicked high cholesterol, WHC). Mice were fed an atherogenic diet; echocardiographic and biochemical data were collected longitudinally. Atherosclerosis and vascular calcification were analyzed histologically in the aorta, aortic sinus and coronary arteries. TNAP mice were also treated with a combination of an atherogenic diet and a specific inhibitor of TNAP (SBI-425). Combined with the ldlr mutation and an atherogenic diet, TNAP-driven arterial calcification led to severe atherosclerosis with 100% morbidity characterized by occlusive coronary artery disease, pathological cardiac hypertrophy with dilated LV and reduced ejection fraction (EF). We detected an interaction between vascular calcification and atherosclerosis in mice with endothelial TNAP overexpression. This interaction was particularly prominent in coronary circulation. Targeting TNAP activity therapeutically helped improve survival and heart function of endothelial TNAP overexpressor mice, however the incomplete inhibition of TNAP by SBI-425 was a limitation of this study. Conclusions: Vascular calcification via TNAP overexpression in endothelial cells promotes coronary atherosclerosis and is pathogenic under conditions of hypercholesterolemia.

scholarly journals JCAD , a Gene at the 10p11 Coronary Artery Disease Locus, Regulates Hippo Signaling in Endothelial Cells

2018 ◽  
Vol 38 (8) ◽  
pp. 1711-1722 ◽  
Author(s):  
Peter D. Jones ◽  
Michael A. Kaiser ◽  
Maryam Ghaderi Najafabadi ◽  
Simon Koplev ◽  
Yuqi Zhao ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Disease Locus ◽  
Hippo Signaling ◽  
Artery Disease

scholarly journals CXCL12 Derived From Endothelial Cells Promotes Atherosclerosis to Drive Coronary Artery Disease

Circulation ◽  
2019 ◽  
Vol 139 (10) ◽  
pp. 1338-1340 ◽  
Author(s):  
Yvonne Döring ◽  
Emiel P.C. van der Vorst ◽  
Johan Duchene ◽  
Yvonne Jansen ◽  
Selin Gencer ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Artery Disease

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.

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