Methylglyoxal-derived advanced glycation end products contribute to negative cardiac remodeling and dysfunction post-myocardial infarction

2017 ◽  
Vol 112 (5) ◽  
Author(s):  
Nick J. R. Blackburn ◽  
Branka Vulesevic ◽  
Brian McNeill ◽  
Cagla Eren Cimenci ◽  
Ali Ahmadi ◽  
...  
Author(s):  
Zhongwei Liu ◽  
Yong Zhang ◽  
Shuo Pan ◽  
Chuan Qiu ◽  
Hao Jia ◽  
...  

Association between receptor for advanced glycation end products (RAGE) and post- myocardial infarction (MI) ventricular arrhythmias (VAs) in diabetes was investigated. Correlation between premature ventricular contractions (PVCs) and serum advanced glycation end products (AGEs) content was analyzed in a cohort consisted of 101 ST segment elevated MI (STEMI) patients. MI diabetic rats were treated with anti- receptor for AGE (RAGE) antibody. Electrocardiography was used to record VAs. Myocytes were isolated from adjacent area around infracted region. Immunofluorescent stains were used to evaluate association between FKBP12.6 (FK506-bindingprotein 12.6) and ryanodine receptor 2 (RyR2). Calcium sparks were evaluated by confocal microscope. Protein expression and phosphorylation were assessed by Western blotting. Calcineurin (CaN) enzymatic activity and RyR2 channel activity were also determined. In the cohort study, significantly increased amount of (PVCs) were found in STEMI patients with diabetes (P<0.05). Serum AGEs concentration was significantly positively correlated with PVCs amount in STEMI patients (r=0.416, P<0.001). Multivariate analysis showed serum AGEs concentration was independently and positively related to frequent PVCs (adjusted hazard ratio, 1.86; 95% CI, 1.09-3.18, P=0.022). In the animal study, increased glucose regulated protein 78 (GRP78) expression, protein kinase RNA-like ER kinase (PERK) phosphorylation, CaN enzymatic activity, FKBP12.6-RyR2 disassociation, RyR2 channel opening and endoplasmic reticulum (ER) calcium releasing were found in diabetic MI animals, which were attenuated by anti-RAGE antibody treatment. This RAGE blocking also significantly lowered the VAs amount in diabetic MI animals. Activation of RAGE- dependent ER stress- mediated PERK/CaN/RyR2 signaling participated in post-MI VAs in diabetes.


PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0209964 ◽  
Author(s):  
Bianca de Moraes Fracasso ◽  
Juliana Oliveira Rangel ◽  
Alessandra Gonçalves Machado ◽  
Fernanda Severo Curuja ◽  
Amanda Lopes ◽  
...  

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Juliana O Rangel ◽  
Bianca Fracasso ◽  
Amanda Phaelante ◽  
Fernanda Curuja ◽  
Daniel Sturza ◽  
...  

Macrophage phenotypes play an important role in post-MI cardiac remodeling. M1 macrophages have a proinflammatory phenotype and are found in the heart early after MI whereas M2 macrophages arise after and replace M1 macrophages in order to mediate the resolution of inflammation and angiogenesis. Advanced glycation end products (AGE) may modulate macrophage polarization but its functional role in the context of post-MI remains incompletely understood. Our goal is to assess whether AGE can polarize macrophages in post-MI and interfere in cardiac remodeling. We have collected experimental data from 68 male Wistar rats (2-3 month-old) divided in 4 groups: sham, MI + 0.9% NaCl (i.p.), MI + methylglyoxal (AGE inducer, 17 mg/kg/day; i.p.); and MI + aminoguanidine (anti-AGE agent, 0.5 g/L in drinking water). Subgroups were euthanized on days 2, 6, and 10 days post-MI. The echocardiographic analysis did not show differences in ejection fraction or akinetic/hypokinetic area among the MI groups. Cytokine levels were assessed by multiplex analysis in cardiac tissue homogenate. There was an increase of proinflammatory cytokine IL-6 on 10th day after surgery in MI group at the remote area, while IL-1β and IL-12 showed reduction compared with the sham group. Anti-inflammatory cytokine IL-10 did not show any difference among the groups. Until now, it is not possible to conclude whether AGE can induce macrophage polarization in vivo. More analyses are necessary to respond our objective.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 434
Author(s):  
Govigerel Bayarsaikhan ◽  
Delger Bayarsaikhan ◽  
Pyung Chun Oh ◽  
Woong Chol Kang ◽  
Bonghee Lee

Cardiovascular disorders, especially acute coronary syndromes, are among the leading causes of mortality worldwide, and advanced glycation end products (AGEs) are associated with cardiovascular disease and serve as biomarkers for diagnosis and prediction. In this study, we investigated the utility of AGEs as prognostic biomarkers for acute myocardial infarction (AMI). We measured AGEs in serum samples of AMI patients (N = 27) using the cupric ion reducing antioxidant capacity (CUPRAC) method on days 0, 2, 14, 30, and 90 after AMI, and the correlation of serum AGE concentration and post-AMI duration was determined using Spearman’s correlation analysis. Compared to total serum protein, the level of CUPRAC reactive AGEs was increased from 0.9 to 2.1 times between 0–90 days after AMI incident. Furthermore, the glycation pattern and Spearman’s correlation analysis revealed four dominant patterns of AGE concentration changes in AMI patients: stable AGE levels (straight line with no peak), continuous increase, single peak pattern, and multimodal pattern (two or more peaks). In conclusion, CUPRAC-reactive AGEs can be developed as a potential prognostic biomarker for AMI through long-term clinical studies.


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