Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening

Eupen, Marcelle G.A. van; Schram, Miranda T.; Sloten, Thomas T. van; Scheijen, Jean L.J.M.; Sep, Simone J. S.; Kallen, Carla; Dagnelie, Pieter C.; Koster, Annemarie; Schaper, Nicolaas C.; Henry, Ronald M.A.; Kroon, Abraham A.; Smit, Andries J.; Stehouwer, Coen D.A.; Schalkwijk, Casper G.

doi:10.1161/hypertensionaha.116.07446

Cited by 53 publications

(57 citation statements)

References 41 publications

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“…However, no association between intima-media thickness and MG-H1 or CRP could be found in these patients [59]. Lastly, an association between skin auto-fluorescence, pentosidine, and carotid-femoral pulse-wave velocity as a parameter of arterial stiffness, were more pronounced in individuals with diabetes mellitus type 2 than in healthy controls [60].…”

Section: Epidemiologic Studies On Cardiovascular Disease and Ages In mentioning

confidence: 71%

Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links

Groener

Oikonomou

Cheko

et al. 2017

Exp Clin Endocrinol Diabetes

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Hyperglycemia explains the development of late diabetic complications in patients with diabetes type 1 and type 2 only partially. Most therapeutic efforts relying on intensive glucose control failed to decrease the absolute risk for complications by more than 10%, especially in patients with diabetes type 2. Therefore, alternative pathophysiological pathways have to be examined, in order to develop more individualized treatment options for patients with diabetes in the future. One such pathway might be the metabolism of dicarbonyls, among them methylglyoxal and the accumulation of advanced glycation end products. Here we review currently available epidemiological data on dicarbonyls and AGEs in association with human diabetes type 1 and type 2.

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Section: Epidemiologic Studies On Cardiovascular Disease and Ages In mentioning

confidence: 71%

Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links

Groener

Oikonomou

Cheko

et al. 2017

Exp Clin Endocrinol Diabetes

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“…Elevated blood pressure may well be a consequence of increased AGE accumulation. A recent study demonstrated that carotid-femoral pulse-wave velocity and central pulse pressure were independently associated with plasma AGEs [43]. Several AGEs are able to form crosslinks within collagen in the vascular wall, which may result in impaired vascular elasticity and increased arterial stiffness, causing blood pressure to rise [44, 45].…”

Section: Discussionmentioning

confidence: 99%

Skin autofluorescence, a non-invasive biomarker for advanced glycation end products, is associated with the metabolic syndrome and its individual components

Waateringe

Slagter

Beek

et al. 2017

Diabetol Metab Syndr

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BackgroundThe metabolic syndrome (MetS) comprises several cardiometabolic risk factors associated with increased risk for both type 2 diabetes and cardiovascular disease. Skin autofluorescence (SAF), a non-invasive biomarker of advanced glycation end products accumulation, is associated with cardiovascular complications in subjects with diabetes. The aim of the present study was to examine the association between SAF and the presence of MetS as well as its individual components in a general population.MethodsFor this cross-sectional analysis, we included 78,671 non-diabetic subjects between 18 and 80 years of age who participated in the LifeLines Cohort Study and had SAF measurement obtained non-invasively using the AGE Reader. MetS was defined according to the revised NCEP ATP III criteria. Students unpaired t test was used to test differences between groups. Both logistic and linear regression analyses were performed in order to test associations between the individual MetS components and SAF.ResultsSubjects with MetS had higher SAF (2.07 ± 0.45 arbitrary units, AU) compared to individuals without MetS (1.89 ± 0.42 AU) (p < 0.001). There was a positive association between the number of MetS components and higher SAF Z-scores (p < 0.001). Individuals in the highest SAF tertile had a higher presence of MetS (OR 2.61; 95% CI 2.48–2.75) and some of the individual components compared to subjects in the lowest SAF tertile. After correction for age, gender, creatinine clearance, HbA1c and smoking status, only elevated blood pressure and low HDL cholesterol remained significantly associated with higher SAF (p = 0.002 and p = 0.001 respectively).ConclusionSkin autofluorescence was associated with the presence of MetS and some of its individual components. In addition, increasing SAF Z-scores were observed with a higher number of MetS components. Prospective studies are needed to establish whether SAF can be used as an (additional) screening tool to predict both cardiovascular disease and type 2 diabetes in high-risk populations.

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“…A possible explanation is that proteinbound pentosidine may, better than the other AGEs in our analyses, reflect the tissue-AGE content. In that line, we previously reported that skin autofluorescence (a non-invasive measurement of skin AGE accumulation) and plasma protein-bound pentosidine were both positively associated with aortic stiffening, while protein-bound CML and CEL were not [38]. Plasma pentosidine also correlated with skin autofluorescence in Japanese haemodialysis patients [39].…”

Section: Discussionmentioning

confidence: 69%

“…For instance, MGO and GO may trigger distinct intracellular signals involved in various cellular functions in cultured endothelial cells, because of differences in their chemical structures [41]. The possibility of different contributions for AGEs in the development of vascular disease was also reported [38]. For instance, via binding to RAGE, AGEs like CML can activate inflammatory pathways (as reviewed in [42]), while cross-linking AGEs such as pentosidine may act via formation of cross-links between extracellular matrix proteins [43,44].…”

Section: Discussionmentioning

confidence: 98%

Associations of dicarbonyl stress with complement activation: the CODAM study

et al. 2020

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Aims/hypothesis Reactive α-dicarbonyl compounds are major precursors of AGEs and may lead to glycation of circulating and/ or cell-associated complement regulators. Glycation of complement regulatory proteins can influence their capacity to inhibit complement activation. We investigated, in a human cohort, whether greater dicarbonyl stress was associated with more complement activation. Methods Circulating concentrations of dicarbonyl stress markers, i.e. α-dicarbonyls (methylglyoxal [MGO], glyoxal [GO] and 3-deoxyglucosone [3-DG]), and free AGEs (N ε -(carboxymethyl)lysine [CML], N ε -(carboxyethyl)lysine [CEL] and N δ -(5hydro-5-methyl-4-imidazolon-2-yl)-ornithine [MG-H1]), and protein-bound AGEs (CML, CEL, pentosidine), as well as the complement activation products C3a and soluble C5b-9 (sC5b-9), were measured in 530 participants (59.5 ± 7.0 years [mean ± SD], 61% men) of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study. Multiple linear regression analyses were used to investigate the associations between dicarbonyl stress (standardised) and complement activation (standardised) with adjustment of potential confounders, including age, sex, lifestyle, use of medication and markers of obesity. In addition, the associations of two potentially functional polymorphisms (rs1049346, rs2736654) in the gene encoding glyoxalase 1 (GLO1), the rate-limiting detoxifying enzyme for MGO, with C3a and sC5b-9 (all standardized) were evaluated. Results After adjustment for potential confounders, plasma concentration of the dicarbonyl GO was inversely associated with sC5b-9 (β −0.12 [95% CI -0.21, −0.02]) and the protein-bound AGE CEL was inversely associated with C3a (−0.17 [−0.25, −0.08]). In contrast, the protein-bound AGE pentosidine was positively associated with sC5b-9 (0.15 [0.05, 0.24]). No associations were observed for other α-dicarbonyls and other free or protein-bound AGEs with C3a or sC5b-9. Individuals with the AG and AA genotype of rs1049346 had, on average, 0.32 and 0.40 SD lower plasma concentrations of sC5b-9 than those with the GG genotype, while concentrations of C3a did not differ significantly between rs1049346 genotypes. GLO1 rs2736654 was not associated with either C3a or sC5b-9. Conclusions/interpretation Plasma concentrations of dicarbonyl stress markers showed distinct associations with complement activation products: some of them were inversely associated with either C3a or sC5b-9, while protein-bound pentosidine was consistently and positively associated with sC5b-9. This suggests different biological relationships of individual dicarbonyl stress markers with complement activation.

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Skin Autofluorescence and Pentosidine Are Associated With Aortic Stiffening

Cited by 53 publications

References 41 publications

Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links

Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links

Skin autofluorescence, a non-invasive biomarker for advanced glycation end products, is associated with the metabolic syndrome and its individual components

Associations of dicarbonyl stress with complement activation: the CODAM study

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