PMID- 22425979
OWN - NLM
STAT- MEDLINE
DCOM- 20120809
LR  - 20220311
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 65
IP  - 5
DP  - 2012 May
TI  - Methylglyoxal promotes oxidative stress and endothelial dysfunction.
PG  - 497-506
LID - 10.1016/j.phrs.2012.03.004 [doi]
AB  - Modern diets can cause modern diseases. Research has linked a metabolite of 
      sugar, methylglyoxal (MG), to the development of diabetic complications, but the 
      exact mechanism has not been fully elucidated. The present study was designed to 
      investigate whether MG could directly influence endothelial function, oxidative 
      stress and inflammation in Wistar and Goto-Kakizaki (GK) rats, an animal model of 
      type 2 diabetes. Wistar and GK rats treated with MG in the drinking water for 3 
      months were compared with the respective control rats. The effects of MG were 
      investigated on NO-dependent vasorelaxation in isolated rat aortic arteries from 
      the different groups. Insulin resistance, NO bioavailability, glycation, a 
      pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) and 
      vascular oxidative stress were also evaluated. Methylglyoxal treated Wistar rats 
      significantly reduced the efficacy of NO-dependent vasorelaxation (p<0.001). This 
      impairment was accompanied by a three fold increase in the oxidative stress 
      marker nitrotyrosine. Advanced glycation endproducts (AGEs) formation was 
      significantly increased as well as MCP-1 and the expression of the receptor for 
      AGEs (RAGE). NO bioavailability was significantly attenuated and accompanied by 
      an increase in superoxide anion immunofluorescence. Methylglyoxal treated GK rats 
      significantly aggravated endothelial dysfunction, oxidative stress, AGEs 
      accumulation and diminished NO bioavailability when compared with control GK 
      rats. These results indicate that methylglyoxal induced endothelial dysfunction 
      in normal Wistar rats and aggravated the endothelial dysfunction present in GK 
      rats. The mechanism is at least in part by increasing oxidative stress and/or 
      AGEs formation with a concomitant increment of inflammation and a decrement in NO 
      bioavailability. The present study provides further evidence for methylglyoxal as 
      one of the causative factors in the pathogenesis of atherosclerosis and 
      development of macrovascular diabetic complication.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Sena, Cristina M
AU  - Sena CM
AD  - Institute of Physiology, University of Coimbra, Portugal; IBILI, Faculty of 
      Medicine, University of Coimbra, Portugal. csena@ci.uc.pt
FAU - Matafome, Paulo
AU  - Matafome P
FAU - Crisostomo, Joana
AU  - Crisostomo J
FAU - Rodrigues, Lisa
AU  - Rodrigues L
FAU - Fernandes, Rosa
AU  - Fernandes R
FAU - Pereira, Paulo
AU  - Pereira P
FAU - Seica, Raquel M
AU  - Seica RM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120316
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (vasodilator-stimulated phosphoprotein)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 722KLD7415 (Pyruvaldehyde)
SB  - IM
MH  - Animals
MH  - Cell Adhesion Molecules/metabolism
MH  - Diabetes Mellitus, Type 2/etiology/pathology/physiopathology
MH  - Endothelium, Vascular/*drug effects/pathology/physiopathology
MH  - Glycation End Products, Advanced/metabolism
MH  - Inflammation/etiology/metabolism
MH  - Male
MH  - Microfilament Proteins/metabolism
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress/drug effects
MH  - Phosphoproteins/metabolism
MH  - Pyruvaldehyde/metabolism/*toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/metabolism
MH  - Vasodilation/drug effects
EDAT- 2012/03/20 06:00
MHDA- 2012/08/10 06:00
CRDT- 2012/03/20 06:00
PHST- 2011/09/16 00:00 [received]
PHST- 2012/02/20 00:00 [revised]
PHST- 2012/03/06 00:00 [accepted]
PHST- 2012/03/20 06:00 [entrez]
PHST- 2012/03/20 06:00 [pubmed]
PHST- 2012/08/10 06:00 [medline]
AID - S1043-6618(12)00044-8 [pii]
AID - 10.1016/j.phrs.2012.03.004 [doi]
PST - ppublish
SO  - Pharmacol Res. 2012 May;65(5):497-506. doi: 10.1016/j.phrs.2012.03.004. Epub 2012 
      Mar 16.