Advanced glycation end products (AGEs) and their soluble receptors (sRAGE) as early predictors of reno-vascular complications in patients with uncontrolled type 2 diabetes mellitus

Farhan, Sinan Subhi; Hussain, Saad Abdulrahman

doi:10.1016/j.dsx.2019.06.019

Cited by 23 publications

(25 citation statements)

References 28 publications

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“…In patients with T2DM, plasma levels of AGEs are elevated, and negatively correlated with endothelium-dependent and endothelium-independent vasodilation (Tan et al, 2002). Moreover, plasma levels of AGEs are approximately 74% higher in patients with T2DM with vascular complications, compared to those with T2DM without vascular complications (Farhan and Hussain, 2019). Activation of RAGE by AGEs also stimulates NADPH oxidase, increasing intracellular ROS generation, subsequently activating NF-kB, resulting in the production of pro-inflammatory and pro-atherogenic mediators, including IL-6, VCAM-1, ICAM-1 and MCP-1 (Barlovic et al, 2010) ( Figure 2).…”

Section: Advanced Glycation End-productsmentioning

confidence: 99%

Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

et al. 2020

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Diabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading to an impairment in endogenous nitric oxide (NO•) generation, together with reductions in NO• bioavailability and NO• responsiveness in the vasculature, platelets and myocardium. The latter impairment of responsiveness to NO•, termed NO• resistance, compromises the ability of traditional NO•-based therapeutics to improve hemodynamic status during diabetes-associated cardiovascular emergencies, such as acute myocardial infarction. Whilst a number of agents can ameliorate (e.g. angiotensin converting enzyme [ACE] inhibitors, perhexiline, statins and insulin) or circumvent (e.g. nitrite and sGC activators) NO• resistance, nitroxyl (HNO) donors offer a novel opportunity to circumvent NO• resistance in diabetes. With a suite of vasoprotective properties and an ability to enhance cardiac inotropic and lusitropic responses, coupled with preserved efficacy in the setting of oxidative stress, HNO donors have intact therapeutic potential in the face of diminished NO• signaling. This review explores the major mechanisms by which hyperglycemia-induced oxidative stress drives NO• resistance, and the therapeutic potential of HNO donors to circumvent this to treat cardiovascular complications in type 2 diabetes mellitus.

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Section: Advanced Glycation End-productsmentioning

confidence: 99%

Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

et al. 2020

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“…These oxidative changes alter genetic expressions that damage pancreatic β cells and induce insulin resistance [5][6][7][8] . Thus, AEGs formation act as one of the key factors that explain the ability of these compounds to alter the chemical and functional properties of various biological structures [9][10][11] . Chronic hyperglycemia contributes significantly to endothelial injury by formation of free radicals, interactions with cellular receptors, or via cross-linking with proteins.…”

Section: Introductionmentioning

confidence: 99%

“…Chronic hyperglycemia contributes significantly to endothelial injury by formation of free radicals, interactions with cellular receptors, or via cross-linking with proteins. The irreversible glycation of subendothelial collagen and other structural proteins changes vase structure and promotes vascular permeability and synthesis of proinflammatory cytokines, leading to diabetic complications such as macrovascular disorders 10,12,13 . Platelets, in turn, adhere to subendothelial components and are activated by cellular signaling, resulting in alteration, secretion and aggregation of the cellular form.…”

Section: Introductionmentioning

confidence: 99%

Coffee intake (Coffea arabica L.) reduces advanced glycation end product (AGEs) formation and platelet aggregation in diabetic rats

Silvério

Pereira

Duarte

et al. 2021

Rev. Ciênc. Farm. Básica Apl.

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Objectives:The study aimed to determine the effect of coffee intake on AGEs formation and platelet aggregation in diabetic Wistar rats. Methods: Coffee powder samples were used to prepare a 10% beverage. Diabetes mellitus was induced in the animals by administering 2% alloxan. All animal experiments were approved by the ethics committee for animal experiments under N°. 420/2012 and 536/2013. Diabetic and non-diabetic rats were divided into 6 groups treated and untreated with coffee (7.2 mL/Kg body weight) and aminoguanidine (AGE inhibiting agent) (100 mg/Kg body weight) for 50 days. After 50 days, the animals were fasted for 12 h and anesthetized (40 mg/Kg sodium pentobarbital) intraperitoneally. Blood samples were collected from the abdominal artery puncture. Hematological parameters (red cells, hemoglobin, hematocrit and leukocyte) and glycemic and HbA1c levels were measured. AGEs quantification (spectrofluorometric method) and the platelet aggregation test (aggregation of cuvettes in a fourchannel platelet aggregometer) were also conducted. The rats' renal function was evaluated by measuring serum urea and creatinine. Results: Data showed that coffee intake had no effect on the hematological parameters. Fasting glucose and HbA1c dosage were significantly higher in diabetic animals compared to non-diabetic animals (confirmed the effectiveness of inducing and maintaining diabetic status). Results showed that coffee reduced AGE formation and platelet aggregation in our animal model, not altering the animals' renal function. Conclusions: These results suggest beneficial effects on vasculopathy, a common complication in diabetic patients.

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“…Decreased levels of circulating sRAGE have been reported in patients with hypertension, metabolic syndrome, coronary artery disease, T1D, T2D, and obesity, suggesting that sRAGE is an early predictor of cardiovascular risk [ 32 , 33 , 34 , 35 , 36 , 37 ]. In T2D, lower plasma sRAGE has been inversely correlated with HbA 1c [ 38 ]. Interestingly, in an apparently healthy population, sRAGE levels declined with age and were inversely associated with body mass index (BMI) [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

“…In T2D, lower plasma sRAGE has been inversely correlated with HbA 1c [ 38 ]. Interestingly, in an apparently healthy population, sRAGE levels declined with age and were inversely associated with body mass index (BMI) [ 38 ]. Alternatively, studies have also demonstrated no difference or elevated total sRAGE levels in T1D and T2D compared with BMI-matched controls with no relationship to necessary measures of insulin sensitivity [ 39 , 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes

et al. 2020

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We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = <35 years old or middle-aged (36–64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications.

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Advanced glycation end products (AGEs) and their soluble receptors (sRAGE) as early predictors of reno-vascular complications in patients with uncontrolled type 2 diabetes mellitus

Cited by 23 publications

References 28 publications

Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

Coffee intake (Coffea arabica L.) reduces advanced glycation end product (AGEs) formation and platelet aggregation in diabetic rats

Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes

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