scholarly journals LipoGlo: A sensitive and specific reporter of atherogenic lipoproteins

2019 ◽  
Author(s):  
James H. Thierer ◽  
Stephen C. Ekker ◽  
Steven A. Farber
Keyword(s):  
Apolipoprotein B ◽  
Fusion Proteins ◽  
Vascular Wall ◽  
Atherosclerotic Cardiovascular Disease ◽  
Specific Approach ◽  
Larval Zebrafish ◽  
Intact Organism ◽  
Luciferase Enzyme ◽  
Lipoprotein Size ◽  
New Strategies

ABSTRACTApolipoprotein-B (APOB) is the structural component of atherogenic lipoproteins, lipid-rich particles that drive atherosclerosis by accumulating in the vascular wall. As atherosclerotic cardiovascular disease is the leading cause of death worldwide, there is an urgent need to develop new strategies to prevent lipoproteins from causing vascular damage. Here we report the LipoGlo system, which uses a luciferase enzyme (NanoLuc) fused to ApoB to monitor several key determinants of lipoprotein atherogenicity including particle abundance, size, and localization. Using LipoGlo, we are able to comprehensively characterize the lipoprotein profile of individual larval zebrafish and collect the first images of atherogenic lipoprotein localization in an intact organism. We discover multiple unexpected extravascular lipoprotein localization patterns, as well as identifypla2g12bas a potent regulator of lipoprotein size. ApoB-fusion proteins thus represent a uniquely sensitive and specific approach to study atherogenic lipoproteins and their genetic and small molecule modifiers.

scholarly journals The action of Metaloproteinases in the Atherosclerotic Diseases

2014 ◽  
Vol 39 (3) ◽  
Author(s):  
Álvaro Luís Müller da Fonseca ◽  
Fernanda Washington de Mendonça Lima ◽  
Ricardo David Couto
Keyword(s):  
Coronary Artery Disease ◽  
Matrix Metalloproteinases ◽  
Inflammatory Markers ◽  
Subclinical Atherosclerosis ◽  
Vascular Wall ◽  
Atherosclerotic Cardiovascular Disease ◽  
The World ◽  
Indirect Indicator ◽  
Artery Disease ◽  
Serum Inflammatory Markers

Cardiovascular diseases represent the main cause of morbidity and mortality in the world and are epidemic events involving the atherosclerosis and coronary artery disease in particular. There are a wide variety of factors and markers associated with the development and aggravation of these diseases, including atherosclerosis. Subclinical Atherosclerosis can be determined by serum inflammatory markers present in the atherogenic process. Such markers can take a direct or indirect indicator role on atherosclerotic cardiovascular disease. The extracellular matrix metalloproteinases are biomarkers closely related into modifying and remodeling of vascular wall and other tissues and can represent predictive value patterns to support diagnosis. This review discusses the function and types of matrix metalloproteinases and its use as an indicator of support for the diagnosis of atherosclerosis.

Autoantibodies against modified apolipoprotein B-100 in relation to low-density lipoprotein size and the metabolic syndrome in otherwise healthy men

Metabolism ◽  
2008 ◽  
Vol 57 (3) ◽  
pp. 362-366 ◽  
Author(s):  
Per Sjögren ◽  
Gunilla N. Fredrikson ◽  
Magdalena Rosell ◽  
Ulf de Faire ◽  
Anders Hamsten ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Healthy Men ◽  
The Metabolic Syndrome ◽  
Lipoprotein Size

scholarly journals Humoral immunity in atherosclerosis and myocardial infarction: from B cells to antibodies

2021 ◽  
Author(s):  
Florentina Porsch ◽  
Ziad Mallat ◽  
Christoph J Binder
Keyword(s):  
Cardiovascular Disease ◽  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Clinical Manifestations ◽  
Vascular Wall ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cell Functions ◽  
Cell Immunity ◽  
B Cell Subsets

Abstract Immune mechanisms are critically involved in the pathogenesis of atherosclerosis and its clinical manifestations. Associations of specific antibody levels and defined B cell subsets with cardiovascular disease activity in humans as well as mounting evidence from preclinical models demonstrate a role of B cells and humoral immunity in atherosclerotic cardiovascular disease. These include all aspects of B cell immunity, the generation of antigen-specific antibodies, antigen presentation and co-stimulation of T cells, as well as production of cytokines. Through their impact on adaptive and innate immune responses and the regulation of many other immune cells, B cells mediate both protective and detrimental effects in cardiovascular disease. Several antigens derived from (oxidised) lipoproteins, the vascular wall and classical autoantigens have been identified. The unique antibody responses they trigger and their relationship with atherosclerotic cardiovascular disease are reviewed. In particular, we focus on the different effector functions of specific IgM, IgG, and IgE antibodies and the cellular responses they trigger and highlight potential strategies to target B cell functions for therapy.

Impact of Serum Apolipoprotein B Measurements on the Risk Management of Atherosclerotic Cardiovascular Disease

2019 ◽  
Vol 10 (11) ◽  
pp. 2268
Author(s):  
Tahrir Etihad Kadium ◽  
Lewai S. Abdulaziz ◽  
Abdulhadi Alrubaie ◽  
Omar J. Ahmed ◽  
Wail A. Abd Al-Hassan
Keyword(s):  
Cardiovascular Disease ◽  
Risk Management ◽  
Apolipoprotein B ◽  
Atherosclerotic Cardiovascular Disease

scholarly journals Discordance between LDL-C and Apolipoprotein B Levels and Its Association with Renal Dysfunction: Insights from a Population-Based Study

2022 ◽  
Vol 11 (2) ◽  
pp. 313
Author(s):  
Mohsen Mazidi ◽  
Richard J. Webb ◽  
Gregory Y. H. Lip ◽  
Andre P. Kengne ◽  
Maciej Banach ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Population Based ◽  
Categorical Variables ◽  
Atherosclerotic Cardiovascular Disease ◽  
Model Assessment ◽  
Logistic Regression Models

Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) are established markers of atherosclerotic cardiovascular disease (ASCVD), but when concentrations are discordant ApoB is the superior predictor. Chronic kidney disease (CKD) is associated with ASCVD, yet the independent role of atherogenic lipoproteins is contentious. Four groups were created based upon high and low levels of ApoB and LDL-C. Continuous and categorical variables were compared across groups, as were adjusted markers of CKD. Logistic regression analysis assessed association(s) with CKD based on the groups. Subjects were categorised by LDL-C and ApoB, using cut-off values of >160 mg/dL and >130 mg/dL, respectively. Those with low LDL-C and high ApoB, compared to those with high LDL-C and high ApoB, had significantly higher body mass index (30.7 vs. 30.1 kg/m2) and waist circumference (106.1 vs. 102.7 cm) and the highest fasting blood glucose (117.5 vs. 112.7 mg/dL), insulin (16.6 vs. 13.1 μU/mL) and homeostatic model assessment of insulin resistance (5.3 vs. 3.7) profiles (all p < 0.001). This group, compared to those with high LDL-C and high ApoB, also had the highest levels of urine albumin (2.3 vs. 2.2 mg/L), log albumin-creatinine ratio (2.2 vs. 2.1 mg/g) and serum uric acid (6.1 vs. 5.6 mg/dL) and the lowest estimated glomerular filtration rate (81.3 vs. 88.4 mL/min/1.73 m2) (all p < 0.001). In expanded logistic regression models, using the low LDL-C and low ApoB group as a reference, those with low LDL-C and high ApoB had the strongest association with CKD, odds ratio (95% CI) 1.12 (1.08–1.16). Discordantly high levels of ApoB are independently associated with increased likelihood of CKD. ApoB remains associated with metabolic dysfunction, regardless of LDL-C.

scholarly journals Correlation of Apo B-48 and Apo B-100 with Oxidized LDL in Men with Central Obesity

2010 ◽  
Vol 2 (2) ◽  
pp. 53
Author(s):  
Maria Diah Fibriani ◽  
Andi Wijaya ◽  
Burhanuddin Bahar
Keyword(s):  
Apolipoprotein B ◽  
Central Obesity ◽  
Oxidized Ldl ◽  
Structural Proteins ◽  
Atherosclerotic Cardiovascular Disease ◽  
Apo B ◽  
The Metabolic Syndrome ◽  
Atherosclerosis Risk ◽  
New Strategy ◽  
Atherosclerosis Development

BACKGROUND: Obesity has a central role in the metabolic syndrome, which raises the risk for atherosclerotic cardiovascular disease (ASVCD). Apo B-48 and Apo B-100 are the necessary structural proteins required for the assembly and secretion of chylomicron and VLDL which have role in atherogenesis. The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B-containing lipoproteins. Oxidation of LDL is a hallmark of atherosclerosis development. The aim of this study was to asses the association between Apo B-48 and Apo B-100 with Oxidized-LDL as marker of atherosclerosis risk in central obesity. We hope that the result of this study can help to make a new strategy for the prevention and treatment of vascular disease.RESULTS: There were 68 patients aged 39.6±7.3 years, Apo B-48 concentration was 7.47±5.36 μg/mL, Apo B-100 was 117.26±25.74 mg/dL, and ox-LDL was 137.05±18.88 U/L. This study showed a significant correlation between Apo B-100 and ox-LDL (r=0.608, p<0.05) and correlation between Apo B-48 and ox-LDL (r=0.171, p<0.05). The levels of Apo B-100 were significantly different between obese with Mets and obese without Mets individuals (p<0.05).CONCLUSIONS: This study suggested that Apo B-100 concentration increase in obese in Mets as compared with obese without Mets. Apo B-48 and Apo B-100 were correlated with Oxidized LDL, but correlation between Apo B-100 and ox-LDL more significant that Apo B-48and ox-LDL.KEYWORDS: obesity, atherogenesis, Apo B-48, Apo B-100, ox-LDL

The immunometabolic role of indoleamine 2,3-dioxygenase in atherosclerotic cardiovascular disease: immune homeostatic mechanisms in the artery wall

2019 ◽  
Vol 115 (9) ◽  
pp. 1408-1415 ◽  
Author(s):  
Daniel F J Ketelhuth
Keyword(s):  
Current Knowledge ◽  
Large Body ◽  
Vascular Wall ◽  
Kynurenine Pathway ◽  
Atherosclerotic Cardiovascular Disease ◽  
Artery Wall ◽  
Indoleamine 2,3 Dioxygenase ◽  
Rate Limiting ◽  
Accumulation Of Lipids

AbstractCoronary heart disease and stroke, the two most common cardiovascular diseases worldwide, are triggered by complications of atherosclerosis. Atherosclerotic plaques are initiated by a maladaptive immune response triggered by accumulation of lipids in the artery wall. Hence, disease is influenced by several non-modifiable and modifiable risk factors, including dyslipidaemia, hypertension, smoking, and diabetes. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in the kynurenine pathway of tryptophan (Trp) degradation, is modulated by inflammation and regarded as a key molecule driving immunotolerance and immunosuppressive mechanisms. A large body of evidence indicates that IDO-mediated Trp metabolism is involved directly or indirectly in atherogenesis. This review summarizes evidence from basic and clinical research showing that IDO is a major regulatory enzyme involved in the maintenance of immunohomeostasis in the vascular wall, as well as current knowledge about promising targets for the development of new anti-atherosclerotic drugs.

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