scholarly journals Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19

2021 ◽  
pp. 126-130
Author(s):  
M.D. Tronko ◽  
S.A. Cherviakova ◽  
V.V. Pushkarev ◽  
Y.B. Belchina ◽  
O.I. Kovzun ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Apolipoprotein B ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Levels ◽  
Optical Wavelength ◽  
Increased Risk ◽  
Patients With Diabetes

Elevated levels of low-density lipoprotein (LDL-X) cholesterol, apolipoprotein B (ApoB), and especially oxidized LDL in plasma are associated with an increased risk of cardiovascular disease (CVD). The aim of the study was to determine the levels of ApoB and oxLDL in the blood of patients with diabetes mellitus (DM), CVD and COVID-19. ApoB and oxLDL were determined using enzyme-linked immunosorbent assay kits (Elabscience, USA). The measurements were performed at an optical wavelength of 450 nm. It was found that ApoB and oxLDL levels in the blood of patients with diabetes and, especially, with COVID-19 are substantially higher than in the blood of healthy people. Blood levels of ApoB and oxLDL are higher in patients with both COVID-19 and diabetes or CVD as com pared to patients with COVID-19 without comorbidities. Thus, the levels of ApoB and oxidized LDL may be the promising markers of severe COVID-19.

Monoclonal antibodies can precipitate low-density lipoprotein. I. Characterization and use in determining apolipoprotein B.

1985 ◽  
Vol 31 (10) ◽  
pp. 1654-1658 ◽  
Author(s):  
S Marcovina ◽  
D France ◽  
R A Phillips ◽  
S J Mao
Keyword(s):  
Monoclonal Antibodies ◽  
Apolipoprotein B ◽  
Polyclonal Antibodies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Radial Immunodiffusion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Density ◽  
Apo B ◽  
Blotting Technique

Abstract We produced 20 mouse monoclonal antibodies against human plasma low-density lipoprotein (LDL). Individually they failed to precipitate LDL in agarose gel by the double-immunodiffusion technique; collectively they did, or as few as two combined monoclonal antibodies could do so. To mimic polyclonal antibodies in determination of apolipoprotein B (apo B) by radial immunodiffusion, a combination of four particular monoclonal antibodies (clones A, B, C, and D) was necessary. We characterized these four clones with respect to temperature dependency, affinity, total binding to 125I-labeled LDL, and specificity to the different species of apolipoprotein B. Two monoclonal antibodies (B and C) bound 100% of 125I-labeled LDL; clones A and D bound 80% and 87%, respectively. All four clones bound maximally to LDL at 4 degrees C. The affinity constants for clones A, B, C, and D were 0.6, 2.1, 3.8, and 2.3 X 10(9) L/mol, respectively. By the Western blotting technique, the four monoclonal antibodies all reacted with the species B-100 and B-74 of apolipoprotein B, and to various degrees with B-48 and B-26. Radial immunodiffusion (chi) and direct enzyme-linked immunosorbent assay (y) with a mixture of the four monoclonal antibodies gave almost identical results for 70 patients: y = 0.921 chi-2.58; r = 0.933.

P5322Oxidized phospholipids on apolipoprotein B-100 among black US adults with and without PCSK9 loss-of-function variants

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Mefford ◽  
S Marcovina ◽  
V Bittner ◽  
M Cushman ◽  
T Brown ◽  
...  
Keyword(s):  
Racial Differences ◽  
Apolipoprotein B ◽  
Population Distribution ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
P Value ◽  
Loss Of Function ◽  
Black Adults ◽  
Lipoprotein A ◽  
Increased Risk

Abstract Background High oxidized phospholipid-apolipoprotein B-100 (OxPL-apoB) levels are associated with an increased risk for coronary heart disease (CHD). Genetic PCSK9 loss-of-function (LOF) variants result in life-long lower levels of LDL-C and lipoprotein(a) and reduced CHD risk, but the association with OxPL-apoB is unknown. Purpose To estimate the association between PCSK9 LOF variants and OxPL-apoB levels among black adults. Methods Genotyping for LOF variants (Y142X and C679X) was conducted for 10,196 black Reasons for Geographic And Racial Differences in Stroke study participants. OxPL-apoB was measured using antibody E06 for all participants with LOF variants (n=241) and randomly selected participants, matched at a 1:3 ratio, without LOF variants (n=723). Low OxPL-apoB was defined as the bottom quartile of the population distribution (<1.6 nM). Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated for the association between PCSK9 LOF variants and low OxPL-apoB levels adjusting for age, sex, and estimated glomerular filtration rate. Results Adults with versus without PCSK9 LOF variants had lower LDL-C and lipoprotein(a) and were less likely to be taking a statin. (Table) A higher proportion of adults with versus without PCSK9 LOF variants had low OxPL-apoB levels (30.3 vs 23.4, p=0.03). After adjustment for covariates, the PR of low OxPL-apoB was increased for participants with compared to without LOF variants (PR 1.31, 95% CI 1.00, 1.72). Characteristics of REGARDS participants PCSK9 loss-of-function variant p-value Yes (n=241) No (n=723) Age, years, mean (SD) 63.7 (9.2) 63.8 (8.6) 0.81 Female, % 61.4 60.6 0.82 Diabetes, % 34.4 27.4 0.04 LDL-C, mg/dL, mean (SD) 85 (32) 118 (37) <0.001 Lp(a), nmol/L, median (25th, 75th percentile) 63.2 (30.4, 119.6) 80.4 (39.7, 138.4) 0.02 Statin use, % 13.3 30.4 <0.001 OxPL-apoB <1.6 nM, % 30.3 23.4 0.03 Abbreviations: LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); LOF, loss-of-function; nM, nanomolar; OxPL-apoB, oxidized phospholipids on apolipoprotein B-100; PCSK9, proprotein convertase subtilisin/kexin type-9; REGARDS, REasons for Geographic And Racial Differences in Stroke; SD, standard deviation. Conclusion Among black adults, PCSK9 LOF variants were associated with lower OxPL-apoB levels. Acknowledgement/Funding Industry/academic collaboration between Amgen Inc., University of Alabama at Birmingham and the Icahn School of Medicine at Mt. Sinai; and U01NS041588

scholarly journals Chlamydia pneumoniae Augments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

2005 ◽  
Vol 73 (7) ◽  
pp. 4315-4322 ◽  
Author(s):  
Kambiz Yaraei ◽  
Lee Ann Campbell ◽  
Xiaodong Zhu ◽  
W. Conrad Liles ◽  
Cho-chou Kuo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cell Death ◽  
Chlamydia Pneumoniae ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Mouse Macrophages ◽  
The Impact

ABSTRACT Chlamydia pneumoniae is a common respiratory pathogen that is associated with an increased risk of cardiovascular disease. However, the mechanisms by which C. pneumoniae contributes to cardiovascular disease have not been determined yet. C. pneumoniae infection may accelerate the death of cells within atherosclerotic lesions and contribute to the formation of unstable lesions. To test this hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded mouse macrophages was investigated. It was observed that RAW 264.7 cells are highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL) and exhibit markers of cell death within 24 h of treatment with as little as 5 μg/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection for 24 to 72 h stimulated both additional binding of annexin V and the uptake of propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on cell death independent of a sustained infection. However, unlike oxidized LDL, C. pneumoniae infection does not activate caspase 3 or induce formation of the mitochondrial transition pore or the fragmentation of DNA, all of which are classical markers of apoptosis. Furthermore, primary bone marrow macrophages isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae kills cells by a caspase-independent pathway and that the process is potentially mediated by activation of TLR-2.

Should we Consider Lipoprotein (a) in Cardiovascular Disease Risk Assessment in Patients with Familial Hypercholesterolaemia?

2019 ◽  
Vol 24 (31) ◽  
pp. 3665-3671 ◽  
Author(s):  
Panagiotis Anagnostis ◽  
Pavlos Siolos ◽  
Dimitrios Krikidis ◽  
Dimitrios G. Goulis ◽  
John C. Stevenson
Keyword(s):  
Cardiovascular Disease ◽  
Familial Hypercholesterolaemia ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Increased Risk

Background: Familial hypercholesterolaemia (FH) is a genetically determined lipid disorder, affecting 1 per 200-500 individuals in the general population. It is significantly and independently associated with an increased risk of Cardiovascular Disease (CVD), although it remains still an underrecognized and undertreated disease. Lipoprotein (a) [Lp(a)] is a low-density-lipoprotein (LDL)-like molecule, containing an additional protein, apolipoprotein (a). Objective: This review aims to present and discuss available data on the role of Lp(a) in patients with FH, in terms of its potential augmentation of CVD risk. Methods: A comprehensive search of the literature was performed to identify studies evaluating the CV effects of Lp(a) in patients with FH. Results: Lp(a) has been recognised as an independent risk factor for CVD, mainly coronary artery disease (CAD). Most, but not all, studies show increased Lp(a) concentrations in adults and children with FH. There is also evidence of an independent association between Lp(a) and CVD (mainly CAD) risk in these patients. Conclusion: Some therapeutic modalities, such as niacin, oestrogens, tibolone and proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors may effectively reduce Lp(a) concentrations by 25-30%, although their clinical benefit of this effect remains to be established.

Metabolic syndrome and diabetes

2019 ◽  
pp. 49-58
Author(s):  
Christoph H. Saely
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
High Risk ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Metabolic Syndrome ◽  
Patients With Diabetes ◽  
Multifactorial Approach

The metabolic syndrome (MetS) and even more so diabetes confer a significantly increased risk of cardiovascular disease. A multifactorial approach is required to improve the prognosis of patients with the MetS or diabetes. Glucose control is essential to reduce microvascular diabetes complications and, over long periods of time, may also lower the risk of cardiovascular events in patients with diabetes. As in other patient populations, lowering low-density lipoprotein (LDL) cholesterol and treating arterial hypertension are paramount interventions to reduce cardiovascular event risk in patients with the MetS and diabetes. Most patients with diabetes must be considered at a very high risk of cardiovascular events, which qualifies them for low LDL cholesterol targets. An-tiplatelet therapy is recommended for patients with the MetS or diabetes who already have established cardiovascular disease. Because the MetS or diabetes confers an extremely high risk of cardiovascular events once cardiovascular disease is established, it is extremely important to intervene early to prevent these patients from developing cardiovascular disease.

scholarly journals GLYCATED LOW-DENSITY LIPOPROTEIN IN DIABETIC AND NON-DIABETIC PATIENTS

2019 ◽  
pp. 123-126
Author(s):  
OMAR ABDULWAHID AL-ANI ◽  
ABDURRAHMAN AL-BAZZAZ
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Diabetic Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Patients ◽  
Low Density ◽  
Serum Samples ◽  
Diabetes Center

Objective: The importance of measuring the blood level of modified low-density lipoprotein (LDL) molecules is an effective method of identifying people at risk of coronary atherosclerosis; this is because, in the early stages of atherosclerosis, lipolysis and oxidative modification have a role in promoting the uptake of these lipids through macrophages; therefore, this research aims to measure the level of glycated LDL (Gly-LDL) in the blood and its association with metabolic parameters of diabetic patients (diabetes mellitus) and non-diabetic (hyperlipidemia). Methods: At a University Diabetes Center in Riyadh, we using routine automatic analysis methods, fasting serum samples were analyzed for 31 patients with Type-2 diabetes and 31 non-diabetic patients for LDL, high-density lipoprotein (HDL), total cholesterol, glycated hemoglobin, glucose, and triglycerides (TG), and using enzyme-linked immunosorbent assay to analyze Gly-LDL for the same sample. Results: The level of serum Gly-LDL in non-diabetic was higher than in diabetic patients (p=0.037). Gly-LDL level correlated significantly with LDL in the diabetic group (p=0.035) and was insignificant with other parameters; moreover, it is significantly correlated with HDL (p=0.048), TG (p=0.035), and very LDL (p=0.03) in the non-diabetic group and insignificant with other parameters. Conclusion: Measuring rates of Gly-LDL can be used in the early detection of cardiovascular disease, especially in people with diabetes, as they are more susceptible to modified and oxidized LDL.

scholarly journals Serum modified HDL was associated with cardiovascular disease in a Japanese community-based cohort

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
T Okamura ◽  
M Sata ◽  
M Iida ◽  
A Kakino ◽  
S Harada ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Density Lipoprotein ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Predictive Marker ◽  
High Density ◽  
Apolipoprotein A1 ◽  
Lipid Lowering ◽  
Increased Risk

Abstract Background Previous studies have shown that high density lipoprotein (HDL) is protective against cardiovascular disease (CVD). However, recent studies suggested that function of HDL was more important than HDL cholesterol levels. The present study aimed to clarify the relationship between modified HDL levels and CVD incidence. Methods LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates modified LDL (low density lipoprotein) activity; however, some lipoproteins with apolipoprotein A1 (Apo A-1) are also bonded to LOX-1. In this study, serum LOX-1 ligand containing Apo A-1 was defined as modified HDL, which were measured by our new development method. We conducted a nested case-control study in a Japanese cohort study, involving 11,002 community dwellers. During 4.0 years follow-up, we observed 127 new CVD onsets. For each CVD case, age and sex matched three controls were randomly selected (N = 381). Serum samples collected at baseline survey stored at − 80 °C were used for the measurement of modified HDL. We estimated multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between modified HDL levels and CVD by conditional logistic regression. Results Modified HDL levels were associated with increased risk of CVD (OR for one unit increase of log transformed modified HDL, 2.05: 95% CI, 1.16-3.62) after adjustment for body mass index, hypertension, diabetes, LDL cholesterol, HDL cholesterol, lipid lowering agents, chronic kidney disease, smoking and alcohol drinking. The magnitude of OR was almost equivalent to those of hypertension and diabetes, which were 2.33 (95% CI, 1.37-3.98) and 2.61 (95% CI, 1.48-4.59), respectively. On the other hands, other lipids markers showed relatively weak associations with CVD. Conclusions Serum modified HDL, i.e., LOX-1 ligand containing Apo A-1, might be a novel predictive marker for CVD in apparently healthy individuals. Key messages Recent epidemiologic studies suggested that function of high-density lipoprotein (HDL) was more important than HDL cholesterol level itself to predict cardiovascular disease. Modified HDL measured by a novel cell-free, non-fluorescent method as LOX-1 ligand containing Apo A-1, was a predictive marker for CVD after adjusting for other traditional risk factors.

scholarly journals Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

2012 ◽  
Vol 302 (11) ◽  
pp. L1200-L1208 ◽  
Author(s):  
Monica Goldklang ◽  
Polina Golovatch ◽  
Tina Zelonina ◽  
Jordis Trischler ◽  
Daniel Rabinowitz ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Oxidized Ldl ◽  
Interleukin 1 ◽  
Low Density Lipoprotein ◽  
Airflow Obstruction ◽  
Density Lipoprotein ◽  
Atherogenic Diet ◽  
Lung Damage ◽  
Increased Risk ◽  
Density Lipoprotein Receptor

Smokers with airflow obstruction have an increased risk of atherosclerosis, but the relationship between the pathogenesis of these diseases is not well understood. To determine whether hypercholesterolemia alters lung inflammation and emphysema formation, we examined the lung phenotype of two hypercholesterolemic murine models of atherosclerosis at baseline and on a high-fat diet. Airspace enlargement developed in the lungs of apolipoprotein E-deficient (Apoe −/− ) mice exposed to a Western-type diet for 10 wk. An elevated number of macrophages and lymphocytes accompanied by an increase in matrix metalloproteinase-9 (MMP-9) activity and MMP-12 expression was observed in the lungs of Apoe −/− mice on a Western-type diet. In contrast, low-density lipoprotein receptor-deficient ( Ldlr −/−) mice did not exhibit lung destruction or inflammatory changes. Most importantly, we revealed augmented expression of the downstream targets of the Toll-like receptor (TLR) pathway, interleukin-1 receptor-associated kinase 1, and granulocyte colony-stimulating factor, in the lungs of Apoe −/− mice fed with a Western-type diet. In addition, we demonstrated overexpression of MMP-9 in Apoe −/− macrophages treated with TLR4 ligand, augmented with the addition of oxidized LDL, suggesting that emphysema in these mice results from the activation of the TLR pathway secondary to known abnormal cholesterol efflux. Our findings indicate that, in Apoe −/− mice fed with an atherogenic diet, abnormal cholesterol efflux leads to increased systemic inflammation with subsequent lung damage and emphysema formation.

scholarly journals Low Density Lipoprotein Cholesterol Is Associated With Increased Risk of Cardiovascular Disease in Participants Over 70 Years Old: A Prospective Cohort Study

2021 ◽  
Author(s):  
xin Su ◽  
Deqiang Zheng ◽  
Meiping Wang ◽  
Yingting Zuo ◽  
Jing Wen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Heart Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Unmeasured Confounding ◽  
Increased Risk

Abstract BackgroundPrevious studies, in which the data were collected about half a century ago, suggested that elevated low density lipoprotein cholesterol (LDL-C) is not associated with increased risk of cardiovascular disease (CVD) in patients over 70 years old. However, what is the relationship between LDL-C and CVD risk in a contemporary population aged over 70 years has not been well examined in China.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative study. In this analysis, participants of CHARLS who did not taking statins and did not have heart disease and stroke at 2011 were include and were followed up to 2018. The outcome of this analysis was occurrence of CVD at follow up, which include heart disease and stroke. Cox regression was used to assess the harmful effect of LDL-C on CVD occurrence. We calculated e-values to quantify the effect of unmeasured confounding on our results.ResultsOf the 9,631 participants, 15.2% (N=1,463) were aged over 70 years and 52.5% (N=5,060) were female. During the 7 years follow-up, 1,437 participants had a first CVD attack. Risk of CVD occurrence increased 8% with each 10 mg/mL elevation in LDL-C in whole participants (adjusted HR, 1.08; 95% CI, 1.06-1.10) and age groups of ≥70 years, 60-69years and <60 years. Similar results were observed in subgroup analyses, in which participants were stratified by sex, hypertension, diabetes and chronic kidney disease. According to the restricted cubic spline, we noted a U-shaped relationship between LDL-C and risk of CVD occurrence in group over 70 years old, however, we further found that in the left side of U-shape curve, LDL-C was not associated with occurrence of CVD and its attribution to CVD occurrence was only 2.1%, which indicated that lower level of LDL-C could not increase the risk of CVD occurrence as it was demonstrated by a U-shape association. E-value analysis suggested robustness to unmeasured confounding.ConclusionsIn contemporary society of China, elevated the level of LDL-C also increased the risk of CVD in participants over 70 years old as in the relatively younger participants. These results should strengthen guideline recommendations for the use of lipid lowering therapies in those elderly.

scholarly journals Correlation of Moderate-Intensity Physical Exercise on Irisin, Oxidized-LDL and HDL Level in ≥50 Years Old Obese Men

2019 ◽  
Vol 11 (3) ◽  
pp. 257-61
Author(s):  
Made Putra Semadhi ◽  
Melisa Intan Barliana ◽  
Dewi Muliaty ◽  
Andi Wijaya
Keyword(s):  
Physical Exercise ◽  
Sports Medicine ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cross Sectional Study ◽  
Moderate Intensity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Moderate Intensity Exercise ◽  
Cross Sectional

BACKGROUND: Irisin is secreted by our muscle during physical exercise, which has been recently studied to be linked with lipid metabolism. The aim of this study was to investigate the role of irisin that interact with the oxidized-low density lipoprotein (ox-LDL) and high density lipoprotein cholesterol (HDL-C) levels that are affected by moderate intensity exercise in obese men aged ≥50 years.METHODS: This was a cross-sectional study with 70 obese men whose age ≥50 years old as participants. Participants were classified into two groups of men with and without physical exercised, based on American College of Sports Medicine (ACSM). Irisin and ox-LDL plasma levels were analyzed using enzyme-linked immunosorbent assay (ELISA), meanwhile the HDL-C serum level was analyzed using homogenous enzymatic methods.RESULTS: The result showed an association between the duration of physical exercise per week and irisin level (R=0.584, p<0.01), also between the duration of physical excercise per week and ox-LDL level (R=-0.274, p<0.05). Meanwhile, there was a negative association between irisin levels and ox-LDL (R=-0.294, p<0.05). Irisin indicated to be correlated with HDL-C (R=0.215, p>0.05).CONCLUSION: Moderate-intensity physical exercise may decrease cardiovascular risk and improve the quality of life among obese subjects aged ≥50 years old, which was indicated by the decrease of ox-LDL and the increase of irisin level. In addition, it can be concluded that the higher the irisin level showed the lower levels of ox-LDL and higher level of HDL-C.KEYWORDS: obesity, elderly, irisin, ox-LDL, HDL-C, physical exercise

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