Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Artery ◽  
Antigenic Determinants ◽  
Modified Ldl ◽  
Circulating Antibodies ◽  
Artery Disease

Aims: To investigate the role of glyoxal modified LDL in the immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardi-ovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the im-munogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high-performance liquid chromatography and electron microscopy. Immuniza-tion studies were carried in New Zealand rabbits. The presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects was analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha-helix content of LDL; increased β sheet formation; increased carbon-yl content and decreased free lysine and arginine content. Modified LDL showed aggrega-tion, generation of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggre-gates. It exhibited high antigenicity and generated specific immune responses that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti-glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited the highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the genera-tion of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.

Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease

2021 ◽  
Vol 22 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antigenic Determinants ◽  
Modified Ldl ◽  
Circulating Antibodies ◽  
Artery Disease

Aims: To investigate role of glyoxal modified LDL in immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardiovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the immunogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high performance liquid chromatography and electron microscopy. Immunization studies were carried in New Zealand rabbits. Presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects were analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha helix content of LDL; increased β sheet formation; increased carbonyl content and decreased free lysine and arginine content. Modified LDL showed aggregation, generation of of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggregates. It exhibited high antigenicity and generated specific immune response that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti- glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the generation of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.

Does exercise training impact clock genes in patients with coronary artery disease and type 2 diabetes mellitus?

2016 ◽  
Vol 23 (13) ◽  
pp. 1375-1382 ◽  
Author(s):  
Eva Steidle-Kloc ◽  
Martin Schönfelder ◽  
Edith Müller ◽  
Sebastian Sixt ◽  
Gerhard Schuler ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Artery ◽  
Exercise Training ◽  
Clock Genes ◽  
Artery Disease ◽  
Training Impact

Analysis of HMGB-1 level before and after providing atorvastatin standard therapy in coronary artery disease patients with type-2 diabetes mellitus compared to without type-2 diabetes mellitus

2021 ◽  
Vol 32 (4) ◽  
pp. 439-446
Author(s):  
Widya Handayani ◽  
Suharjono ◽  
Mohammad Yogiarto
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Artery ◽  
High Mobility ◽  
Pleiotropic Effect ◽  
Serum Samples ◽  
Artery Disease

Abstract Objectives Coronary artery disease (CAD) is one of the main causes of death from cardiovascular disease, because heart attacks result in atherosclerosis which causes narrowing of the arteries. Atorvastatin has a pleiotropic effect as anti-inflammatory through one of the target levels of High Mobility Group Box-1 (HMGB-1). This prospective observational study aimed to analyze the effect of atorvastatin on serum HMGB-1 levels in CAD. Methods Samples were collected from prospective observation pre–post study in May–July 2018 with consecutive sampling method. Serum HMGB-1 levels were measured in patients with CAD who were given atorvastatin for CAD with type-2 diabetes mellitus compared without type-2 diabetes mellitus in a patient ward. Blood was collected on admission day and before the patient left the hospital. After centrifugation, serum samples were stored at −80 °C before measurement. We used an ELISA kit (IBL International) to determine HMGB-1 concentrations. This research protocol has been approved by the Ethical Committee of Dr. Soetomo General Hospital, Surabaya. Results We enrolled 38 patients and divided them into two groups which 19 patients on CAD with type-2 diabetes mellitus and 19 patients without diabetes mellitus. Serum HMGB-1 levels in CAD with type-2 diabetes mellitus were increased significantly (p = 0.049) and not significantly decreased in CAD without type-2 diabetes mellitus (p = 0.480). The HMGB-1 level was not significantly different between the two groups (p = 0.210). Conclusions HMGB-1 levels after providing atorvastatin in CAD with type-2 diabetes mellitus increased significantly, meanwhile, in CAD without type-2 diabetes mellitus did not decrease significantly. The HMGB-1 level was not significantly different between the two groups. Longer time and more point for the collected sample needed for further research.

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