Glycated LDL Concentrations in Non-Diabetic and Diabetic Subjects Measured with Monoclonal Antibodies Reactive with Glycated Apolipoprotein B Epitopes

The potential importance of the non-enzymatic glycation of low density lipoproteins (LDL) in atherogenesis and in the accelerated atherosclerosis associated with diabetes is well recognized. However, it has been difficult to evaluate LDL glycation in the clinical setting because of the lack of suitable methods. To approach this problem, we produced monoclonal antibodies, designated ES12, that recognize glycated apolipoprotein B epitopes in the LDL complex in human plasma. Here we report the use of these antibodies in a competitive enzyme-linked immunosorbent assay (ELISA) to measure glycated LDL concentrations in plasma from non-diabetic and diabetic subjects. In this assay, glycated LDL in the soluble phase inhibits binding of the ES12 antibody to glycated LDL immobilized to microtitre wells, whereas other glycated proteins and non-glycated LDL do not compete. A linear dose-response relationship for 10-125 ng glycated LDL per well allows the construction of standard curves, from which the concentration of glycated LDL in human plasma can be determined. The mean concentration of glycated LDL in samples from non-diabetic subjects was 21.8 +/- 0.9 mg/l, increasing to 40.8 +/- 2.6 mg/l in samples from patients with type II diabetes, comprising 1.9-4.8% and 3.2-14.8%, respectively, of total apolipoprotein B. Glycated LDL concentrations in samples from diabetic patients correlated positively and significantly with other indices of glycaemic status. The results indicate that circulating glycated LDL, which may have diagnostic and pathophysiologic importance, is increased in diabetes with attendant hyperglycaemia. The results further indicate that the described monoclonal antibody-based competitive ELISA affords a simple and reproducible method for quantitative measurement of glycated LDL.

• Publication year

  1993

• Venue

  European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1515/cclm.1993.31.11.707PMID 7508270
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Immunologic detection and measurement of glycated apolipoprotein B with site specific monoclonal antibodies.

  1993cited by this paper
• Increased oxidizability of plasma lipoproteins in diabetic patients can be decreased by probucol therapy and is not due to glycation.

  1992cited by this paper
• Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects.

  1992cited by this paper
• Glycated low density lipoprotein catabolism is increased in rabbits with alloxan-induced diabetes mellitus

  1992cited by this paper
• Oxidized Low Density Lipoproteins: a Role in the Pathogenesis of Atherosclerosis in Diabetes?

  1991cited by this paper
• Production and characterization of monoclonal antibodies against non-A1c glycated hemoglobin.

  1991cited by this paper
• A truncated species of apolipoprotein B (B67) in a kindred with familial hypobetalipoproteinemia.

  1991cited by this paper
• Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes.

  1990cited by this paper
• Atherosclerosis. Scavenging for receptors.

  1990cited by this paper
• Metabolism of very low- and low-density lipoproteins isolated from normolipidaemic Type 2 (non-insulin-dependent) diabetic patients by human monocyte-derived macrophages

  1990cited by this paper
• Scavenging for receptors

  1990cited by this paper
• A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein.

  1989cited by this paper
• Interaction of very-low-density lipoprotein isolated from type I (insulin-dependent) diabetic subjects with human monocyte-derived macrophages.

  1989cited by this paper
• The use of monoclonal antibodies to localize the low density lipoprotein receptor-binding domain of apolipoprotein B.

  1989cited by this paper
• Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.

  1989cited by this paper
• Production and characterization of monoclonal antibodies against human glycoalbumin.

  1989cited by this paper
• Book ReviewAmbulatory Pediatric Care

  1989cited by this paper
• Non-enzymatic glycosylation of low-density lipoprotein. Results of an affinity chromatography method

  1988cited by this paper
• Glycation of proteins as a source of superoxide.

  1988cited by this paper
• Glycosylation of Low-Density Lipoprotein Enhances Cholesteryl Ester Synthesis in Human Monocyte-Derived Macrophages

  1988cited by this paper
• Monosaccharide autoxidation: A potential source of oxidative stress in diabetes?: Model reactions with nucleotides and protein

  1987cited by this paper
• Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by low-density lipoproteins from Type 1 (insulin-dependent) diabetic patients: the influence of non-enzymatic glycosylation of low-density lipoproteins

  1987cited by this paper
• Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis.

  1987cited by this paper
• Turnover and tissue sites of degradation of glucosylated low density lipoprotein in normal and immunized rabbits.

  1987cited by this paper
• Impaired hepatocyte binding, uptake and degradation of glucosylated low-density lipoproteins.

  1986cited by this paper
• The complete sequence and structural analysis of human apolipoprotein B‐100: relationship between apoB‐100 and apoB‐48 forms.

  1986cited by this paper
• Glycosylation of low density lipoprotein in patients with Type I (insulin-dependent) diabetes: Correlations with other parameters of glycaemic control

  1986cited by this paper
• Molecular weights of apoprotein B obtained from human low-density lipoprotein (apoprotein B-PI) and from rat very low density lipoprotein (apoprotein B-PIII).

  1985cited by this paper
• Interaction of human endothelial cells with elevated glucose concentrations and native and glycosylated low density lipoproteins

  1984cited by this paper
• Glucosylation of Low-Density Lipoproteins to an Extent Comparable to That Seen in Diabetes Slows Their Catabolism

  1984cited by this paper
• Apolipoprotein B: structural and metabolic heterogeneity.

  1983cited by this paper
• Receptor-mediated catabolism of low density lipoprotein in man. Quantitation using glucosylated low density lipoprotein.

  1983cited by this paper
• Glycosylation of LDL decreases its ability to interact with high-affinity receptors of human fibroblasts in vitro and decreases its clearance from rabbit plasma in vivo.

  1982cited by this paper
• Specificity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins.

  1982cited by this paper
• Glycosylation of human LDL and its metabolism in human skin fibroblasts.

  1982cited by this paper
• Surface binding, internalization and degradation by cultured human fibroblasts of low density lipoproteins isolated from Type 1 (insulin-dependent) diabetic patients: Changes with metabolic control

  1982cited by this paper
• Nonenzymatic Glucosylation of Low-Density Lipoprotein Alters Its Biologic Activity

  1982cited by this paper
• Regulation of plasma cholesterol by lipoprotein receptors.

  1981cited by this paper
• Nonenzymatic Glycosylation of Low Density Lipoproteins In Vitro: Effects on Cell-interactive Properties

  1981cited by this paper
• Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages.

  1980cited by this paper
• Heterogeneity of apolipoprotein B: isolation of a new species from human chylomicrons.

  1980cited by this paper
• Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition.

  1979cited by this paper
• The low-density lipoprotein pathway and its relation to atherosclerosis.

  1977cited by this paper
• Studies on the metabolism of plasma proteins in the nephrotic syndrome. II. The lipoproteins.

  1958cited by this paper

• Modification of lipoprotein metabolism and function driving atherogenesis in diabetes.

  2024cites this paper
• Novel Biomarkers for Atherosclerotic Disease: Advances in Cardiovascular Risk Assessment

  2023cites this paper
• The Reciprocal Relationship between LDL Metabolism and Type 2 Diabetes Mellitus

  2021cites this paper
• 21 Modified Forms of LDL in Plasma

  2018cites this paper
• Biophysical and biochemical studies on glycoxidatively modified human low density lipoprotein.

  2018cites this paper
• Corrected fructosamine , corrected glycated albumin and glycated β-lipoprotein / β-lipoprotein ratio in patients with microvascular complications of type 2 diabetes mellitus

  2016cites this paper
• Serum fructosamine, serum glycated albumin and serum glycated β-lipoprotein in type 2 diabetes mellitus patients with and without microvascular complications

  2016cites this paper
• Lipoprotein Glycation in Diabetes Mellitus

  2014cites this paper
• Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease

  2014cites this paper
• Modified lipoproteins as biomarkers of cardiovascular risk in diabetes mellitus.

  2013cites this paper
• HDL functionality and LDL quality : the influence of obesity, obstructive sleep apnoea and pharmacological intervention

  2013cites this paper
• Modified lipoproteins as biomarkers of cardiovascular risk in diabetes mellitus.

  2013cites this paper
• Impact of the LDL subfraction phenotype on Lp-PLA2 distribution, LDL modification and HDL composition in type 2 diabetes

  2013cites this paper
• Apolipoproteins A-I, B, and C-III in young adult Cherokee with metabolic syndrome with or without type 2 diabetes.

  2013cites this paper
• Electronegative LDL: a useful biomarker of cardiovascular risk?

  2012cites this paper
• A history of HbA 1 c through Clinical Chemistry and Laboratory Medicine

  2012cites this paper
• Modified Forms of LDL in Plasma

  2012cites this paper
• A history of HbA1c through Clinical Chemistry and Laboratory Medicine

  2012cites this paper
• Susceptibility of LDL and its subfractions to glycation

  2011cites this paper
• Inhibiting low-density lipoprotein glycation ameliorates increased cholesteryl ester synthesis in macrophages and hypercholesterolemia and aortic lipid peroxidation in streptozotocin diabetic rats.

  2010cites this paper
• Inhibiting LDL glycation ameliorates increased cholesteryl ester synthesis in macrophages and hypercholesterolemia and aortic lipid peroxidation in streptozotocin diabetic rats

  2010cites this paper
• Glycation of LDL in non-diabetic people: Small dense LDL is preferentially glycated both in vivo and in vitro.

  2009cites this paper
• Evaluation of Serum Biomarkers in Nutritional Disorders: Glycated Apolipoprotein B, Fasting Serum Glucose, Fructosamine, Stable and Labile Glycated Hemoglobin in Diabetic and Non-Diabetic Subjects

  2008cites this paper
• Glycation as an atherogenic modification of LDL

  2008cites this paper
• Glycated apolipoprotein B and myocardial infarction.

  2007cites this paper
• Non enzymatic glycated proteins in the blood and cardiovascular disease.

  2007cites this paper
• Inhibition by L-arginine and spermidine of hemoglobin glycation and lipid peroxidation in rats with induced diabetes.

  2006cites this paper
• The expression of apolipoprotein B epitopes is normal in LDL of diabetic and end-stage renal disease patients

  2006cites this paper
• Amadori-modified glycated serum proteins and accelerated atherosclerosis in diabetes: pathogenic and therapeutic implications.

  2006cites this paper
• Glucose-induced up-regulation of CD36 mediates oxidative stress and microvascular endothelial cell dysfunction

  2005cites this paper
• Towards a New Glycation Index

  2005cites this paper
• Increased Plasma Glycated Low-Density Lipoprotein Concentrations in Diabetes: A Marker of Atherogenic Risk

  2004cites this paper
• Dilazep and fenofibric acid inhibit MCP-1 mRNA expression in glycoxidized LDL-stimulated human endothelial cells.

  2003cites this paper
• Diabetic LDL triggers apoptosis in vascular endothelial cells.

  2003cites this paper
• Improved glucose control decreases the interaction of plasma low-density lipoproteins with arterial proteoglycans.

  2002cites this paper
• Glycoxidized low-density lipoprotein enhances monocyte chemoattractant protein-1 mRNA expression in human umbilical vein endothelial cells: relation to lysophosphatidylcholine contents and inhibition by nitric oxide donor.

  2002cites this paper
• A comparative study of cultured smooth muscle cell proliferation and injury, utilizing glycated low density lipoproteins with slight oxidation, auto-oxidation, or extensive oxidation.

  2000cites this paper
• Glycation of plasma low density lipoproteins increases interaction with arterial proteoglycans.

  1999cites this paper
• Antibodies to oxidized LDL and LDL-containing immune complexes as risk factors for coronary artery disease in diabetes mellitus.

  1999cites this paper
• Measuring Glycated Proteins: Clinical and Methodological Aspects

  1999cites this paper
• Glycolaldehyde-modified low density lipoprotein leads macrophages to foam cells via the macrophage scavenger receptor.

  1998cites this paper
• Short-term variations of serum glycated apolipoprotein B.

  1998cites this paper
• Massive glycation of protein HC, a low molecular weight lipocalin, in non‐diabetic individuals

  1997cites this paper
• Glycated low‐density lipoprotein and atherogenesis: the missing link between diabetes mellitus and hypercholesterolaemia?

  1997cites this paper
• [Non-enzymatic glycosylation in diabetes mellitus].

  1997cites this paper
• A monoclonal antibody-based enzyme immunoassay for the measurement of native and glycated apolipoprotein B-containing particles.

  1997cites this paper
• Role of glycated low density lipoprotein in mesangial extracellular matrix synthesis.

  1997cites this paper
• Increased glycation of plasma lipoproteins in diabetic cynomolgus monkeys.

  1996cites this paper
• Oxidative Stress and Lipids in Diabetes: A Role in Endothelium Vasodilator Dysfunction?

  1996cites this paper
• A Diabetes Potpourri, Part 2

  1995cites this paper
• Enhanced susceptibility of low-density lipoprotein to in vitro oxidation in type 1 and type 2 diabetic patients.

  1995cites this paper
• Immunological detection of glycated proteins in normal and streptozotocin-induced diabetic rats using anti hexitol-lysine IgG.

  1995cites this paper
• Nonenzymic glycation of apolipoprotein B in patients with insulin- and noninsulin-dependent diabetes mellitus.

  1995cites this paper
• Lipoprotein Glycation and Its Metabolic Consequences

  1992cites this paper