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Impact of Atherosclerosis- and Diabetes-Related Dicarbonyls on Vascular Endothelial Permeability: A Comparative Assessment.

ABSTRACT: Malondialdehyde (MDA), glyoxal (GO), and methylglyoxal (MGO) levels increase in atherosclerosis and diabetes patients. Recent reports demonstrate that GO and MGO cause vascular endothelial barrier dysfunction whereas no evidence is available for MDA.To compare the effects of MDA, GO, or MGO on endothelial permeability, we used human EA.hy926 endothelial cells as a standard model. To study cortical cytoplasm motility and cytoskeletal organization in endothelial cells, we utilized time-lapse microscopy and fluorescent microscopy. To compare dicarbonyl-modified protein band profiles in these cells, we applied Western blotting with antibodies against MDA- or MGO-labelled proteins.MDA (150-250??M) irreversibly suppressed the endothelial cell barrier, reduced lamellipodial activity, and prevented intercellular contact formation. The motile deficiency of MDA-challenged cells was accompanied by alterations in microtubule and microfilament organization. These detrimental effects were not observed after GO or MGO (250??M) administration regardless of confirmed modification of cellular proteins by MGO.Our comparative study demonstrates that MDA is more damaging to the endothelial barrier than GO or MGO. Considering that MDA endogenous levels exceed those of GO or MGO and tend to increase further during lipoperoxidation, it appears important to reduce oxidative stress and, in particular, MDA levels in order to prevent sustained vascular hyperpermeability in atherosclerosis and diabetes patients.

SUBMITTER: Samsonov MV

PROVIDER: S-EPMC5643129 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Impact of Atherosclerosis- and Diabetes-Related Dicarbonyls on Vascular Endothelial Permeability: A Comparative Assessment.

Samsonov Mikhail V MV Khapchaev Asker Y AY Vorotnikov Alexander V AV Vlasik Tatyana N TN Yanushevskaya Elena V EV Sidorova Maria V MV Efremov Evgeniy E EE Lankin Vadim Z VZ Shirinsky Vladimir P VP

Oxidative medicine and cellular longevity 20171002

<h4>Background</h4>Malondialdehyde (MDA), glyoxal (GO), and methylglyoxal (MGO) levels increase in atherosclerosis and diabetes patients. Recent reports demonstrate that GO and MGO cause vascular endothelial barrier dysfunction whereas no evidence is available for MDA.<h4>Methods</h4>To compare the effects of MDA, GO, or MGO on endothelial permeability, we used human EA.hy926 endothelial cells as a standard model. To study cortical cytoplasm motility and cytoskeletal organization in endothelial ...[more]

PMID: 29098058

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Project description:Endothelial glycocalyx perturbation contributes to increased vascular permeability. In the present study we set out to evaluate whether: (1) glycocalyx is perturbed in individuals with type 2 diabetes mellitus, and (2) oral glycocalyx precursor treatment improves glycocalyx properties.Male participants with type 2 diabetes (n = 10) and controls (n = 10) were evaluated before and after 2 months of sulodexide administration (200 mg/day). The glycocalyx dimension was estimated in two different vascular beds using sidestream dark field imaging and combined fluorescein/indocyanine green angiography for sublingual and retinal vessels, respectively. Transcapillary escape rate of albumin (TER(alb)) and hyaluronan catabolism were assessed as measures of vascular permeability.Both sublingual dimensions (0.64 [0.57-0.75] ?m vs 0.78 [0.71-0.85] ?m, p < 0.05, medians [interquartile range]) and retinal glycocalyx dimensions (5.38 [4.88-6.59] ?m vs 8.89 [4.74-11.84] ?m, p < 0.05) were reduced in the type 2 diabetes group compared with the controls whereas TER(alb) was increased (5.6 ± 2.3% vs 3.7 ± 1.7% in the controls, p < 0.05). In line with these findings, markers of hyaluronan catabolism were increased with diabetes (hyaluronan 137 ± 29 vs 81 ± 8 ng/ml and hyaluronidase 78 ± 4 vs 67 ± 2 U/ml, both p < 0.05). Sulodexide increased both the sublingual and retinal glycocalyx dimensions in participants with diabetes (to 0.93 [0.83-0.99] ?m and to 5.88 [5.33-6.26] ?m, respectively, p < 0.05). In line, a trend towards TER(alb) normalisation (to 4.0 ± 2.3%) and decreases in plasma hyaluronidase (to 72 ± 2 U/ml, p < 0.05) were observed in the diabetes group.Type 2 diabetes is associated with glycocalyx perturbation and increased vascular permeability, which are partially restored following sulodexide administration. Further studies are warranted to determine whether long-term treatment with sulodexide has a beneficial effect on cardiovascular risk.www.trialregister.nl NTR780/ http://isrctn.org ISRCTN82695186An unrestricted Novartis Foundation for Cardiovascular Excellence grant (2006) to M. Nieuwdorp/E. S. G. Stroes, Dutch Heart Foundation (grant number 2005T037).

Dataset Information

Impact of Atherosclerosis- and Diabetes-Related Dicarbonyls on Vascular Endothelial Permeability: A Comparative Assessment.

Publications

Impact of Atherosclerosis- and Diabetes-Related Dicarbonyls on Vascular Endothelial Permeability: A Comparative Assessment.

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