Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome

Liu, Jianghai; Wang, Rui; Desai, Kaushik; Wu, Lingyun

doi:10.1093/cvr/cvr239

Cited by 59 publications

(76 citation statements)

References 39 publications

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“…It was reported that the expressions of GLUT5 (fructose transporter) and an MGO synthase, aldolase B, increased in SHR aorta, while the expression of other MGO synthases including SSAO or CYP 2E1 and plasma glucose level did not increase (23,24). It was thus proposed that increased MGO accumulation was mediated via aldolase B through increased fructose transporting in vascular tissues of SHR.…”

Section: Discussionmentioning

confidence: 98%

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

et al. 2012

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Abstract. Methylglyoxal (MGO) is a metabolite of glucose and perhaps mediates diabetesrelated macrovascular complications including hypertension. In the present study, we examined if MGO accumulation affects vascular reactivity of isolated mesenteric artery from spontaneously hypertensive rats (SHR). Five-week-old SHR were treated with an MGO scavenger, aminoguanidine (AG), for 5 weeks. AG partially normalized increased blood pressure in SHR. In mesenteric artery from SHR treated with AG, increased accumulation of MGO-derived advanced glycation end-products was reversed. In mesenteric artery from SHR, AG normalized impaired acetylcholine (ACh)-induced relaxation and increased angiotensin (Ang) II-induced contraction. Reactive oxygen species (ROS) production increased in SHR mesenteric artery, and acute treatment with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor augmented AChinduced relaxation. Protein expression of NOX1 and Ang II type 2 receptor (AT2R) increased in SHR mesenteric artery, which was normalized by AG. Acute treatment with an AT2R blocker but not a NOX inhibitor normalized the increased Ang II-induced contraction in SHR mesenteric artery. The present results demonstrate that MGO accumulation in mesenteric artery may mediate development of hypertension in SHR at least in part via increased ROS-mediated impairment of endothelium-dependent relaxation and AT2R-mediated increased Ang II contraction.

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Section: Discussionmentioning

confidence: 98%

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

et al. 2012

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“…It has recently been argued that all therapeutic strategies for the prevention of complications associated with diabetes rely on the premise that the deleterious effects of high glucose levels and an enhanced metabolic flux are mediated by the generation of toxic metabolites (3,4). Of these, reactive a-dicarbonyls like MG are among the most important (6).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, in the setting of diabetes, excessive glycolytic flux with reduced activity of GAPDH (5) and an overactive polyol pathway (4) leads to the accumulation of triose phosphate intermediates and their spontaneous fragmentation into MG (5). The proatherogenic effects of fructose feeding and the metabolic syndrome may also be partly ascribed to increased generation of MG through the polyol pathway (4). MG production may also rise in the absence of hyperglycemia via oxidation of aminoacetone (generated during protein catabolism) by semicarbazide-sensitive amine oxidase, the oxidation of ketone bodies by myeloperoxidase, and/or the cytochrome P450-mediated oxidation of acetone (generated from lipolysis).…”

Section: Discussionmentioning

confidence: 99%

“…A number of metabolic and hemodynamic factors contribute to accelerated atherosclerosis in the setting of diabetes. One key pathway is the increased production of reactive dicarbonyls generated from triose phosphate intermediates of glycolysis, glycerol and ketone peroxidation, overactivation of the polyol pathway, and the degradation of glycated proteins (3)(4)(5)(6). In experimental diabetes, circulating and tissue levels of methylglyoxal (MG) are three to five times higher than in the nondiabetic state (7,8).…”

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confidence: 99%

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Dicarbonyl Stress in the Absence of Hyperglycemia Increases Endothelial Inflammation and Atherogenesis Similar to That Observed in Diabetes

et al. 2014

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The deleterious effects of high glucose levels and enhanced metabolic flux on the vasculature are thought to be mediated by the generation of toxic metabolites, including reactive dicarbonyls like methylglyoxal (MG). In this article, we demonstrate that increasing plasma MG to levels observed in diabetic mice either using an exogenous source (1% in drinking water) or generated following inhibition, its primary clearance enzyme, glyoxalase-1 (with 50 mg/kg IP bromobenzyl-glutathione cyclopentyl diester every second day), was able to increase vascular adhesion and augment atherogenesis in euglycemic apolipoprotein E knockout mice to a similar magnitude as that observed in hyperglycemic mice with diabetes. The effects of MG appear partly mediated by activation of the receptor for advanced glycation end products (RAGE), as deletion of RAGE was able to reduce inflammation and atherogenesis associated with MG exposure. However, RAGE deletion did not completely prevent inflammation or vascular damage, possibly because the induction of mitochondrial oxidative stress by dicarbonyls also contributes to inflammation and atherogenesis. Such data would suggest that a synergistic combination of RAGE antagonism and antioxidants may offer the greatest utility for the prevention and management of diabetic vascular complications.

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“…Excessive levels of the glycolysis metabolite methylglyoxal (MG) in vivo, that contribute to increased carbonyl stress, are associated with conditions such as diabetes, renal failure, obesity and metabolic syndrome [4][5][6][7][8][9]. In diabetes, increased levels of MG are implicated in the pathogenesis of vascular complications such as hypertension [10], impaired microcirculation [11], and thrombosis [12].…”

Section: Introductionmentioning

confidence: 99%

Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Qadri

Shao‐Horn

Cayabyab

et al. 2014

Cardiovasc Diabetol

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Background: Excessive levels of methylglyoxal (MG) encountered in diabetes foster enhanced leukocyte-endothelial cell interactions, mechanisms of which are incompletely understood. MG genomically upregulates endothelial serum-and glucocorticoid-inducible kinase 1 (SGK1) which orchestrates leukocyte recruitment by regulating the activation and expression of transcription factors and adhesion molecules. SGK1 regulates a myriad of ion channels and carriers including the Na

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Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome

Abstract: Upregulation of aldolase B by accumulated fructose is a common mechanism for MG overproduction in VSMCs and aorta in different models of metabolic syndrome.

Cited by 59 publications

References 39 publications

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

Dicarbonyl Stress in the Absence of Hyperglycemia Increases Endothelial Inflammation and Atherogenesis Similar to That Observed in Diabetes

Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

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