Advanced glycation end products upregulate angiogenic and pro-inflammatory cytokine production in human monocyte/macrophages

Pertyńska−Marczewska, Magdalena; Kiriakidis, Serafim; Wait, Robin; Beech, Jonathan T; Feldmann, Marc; Paleolog, Ewa

doi:10.1016/j.cyto.2004.06.006

Cited by 80 publications

(62 citation statements)

References 51 publications

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“…AGE have previously been shown to have significant direct effects on endothelial cells, including increased expression and release of VCAM-1 (17,43), tissue factor (44), and a host of procoagulant and vasoactive factors and cytokines (45). A decrease of eNOS activity has been a prominent response to AGE demonstrated both in vitro and in vivo (16,27).…”

Section: Discussionmentioning

confidence: 99%

Endothelial Dysfunction in Patients with Chronic Kidney Disease Results from Advanced Glycation End Products (AGE)-Mediated Inhibition of Endothelial Nitric Oxide Synthase through RAGE Activation

Linden

Cai

et al. 2008

Clinical Journal of the American Society of Nephrology

153

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Background and objectives: Advanced glycation end products, known pro-inflammatory and pro-oxidative compounds that accumulate in patients with chronic kidney disease, may play a major role in their high prevalence of endothelial dysfunction and subsequent cardiovascular disease. This study examined the association of advanced glycation end product accumulation with cellular receptor for advanced glycation end product expression and endothelial dysfunction as well as the mechanisms of this association in chronic kidney disease.Design, setting, participants, & measurements: A cross-sectional study was conducted of ambulatory patients without diabetes and with different stages of chronic kidney disease (n ‫؍‬ 51), compared with gender-and age-matched healthy subjects. Fasting blood was obtained for measurement of advanced glycation end products and mRNA receptor for advanced glycation end product expression in peripheral blood mononuclear cells. Endothelial reactivity was assessed by the microcirculatory response to local ischemia (postocclusive reactive hyperemia) and local hyperthermia (thermal hyperemia). Sera were pooled and passed through affinity columns to separate advanced glycation end product-rich fractions, which were incubated with human aortic endothelial cells, with or without blockade of receptor for advanced glycation end product, to measure their effect on endothelial nitric oxide synthase.Results: Glomerular filtration rate correlated with serum advanced glycation end product, mRNA receptor for advanced glycation end product levels, postocclusive reactive hyperemia, and thermal hyperemia. Serum advanced glycation end product correlated with receptor for advanced glycation end product and inversely with postocclusive reactive hyperemia. Advanced glycation end product-rich fractions from chronic kidney disease sera suppressed endothelial nitric oxide synthase expression of human aortic endothelial cells compared with sera from healthy subjects, an effect abrogated by receptor for advanced glycation end product blockade.Conclusions: This study demonstrates for the first time an association of excess advanced glycation end product burden with increased peripheral blood mononuclear cell mRNA receptor for advanced glycation end product and in vivo endothelial dysfunction in patients with chronic kidney disease. Endothelial dysfunction in chronic kidney disease may be partly mediated by advanced glycation end product-induced inhibition of endothelial nitric oxide synthase through receptor for advanced glycation end product activation.

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Section: Discussionmentioning

confidence: 99%

Endothelial Dysfunction in Patients with Chronic Kidney Disease Results from Advanced Glycation End Products (AGE)-Mediated Inhibition of Endothelial Nitric Oxide Synthase through RAGE Activation

Linden

Cai

et al. 2008

Clinical Journal of the American Society of Nephrology

153

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“…Acute hyperglycemia may lead to intracellular formation of CML and activation of MAPKs in peripheral monocytes [22]. CML is a dominant AGEs [23] as well as a biomarker of oxidative stress in vivo [24], which can accumulate in tissue proteins and contribute to the progression of inflammation [18,24]. Numerous animal experiments [25] have shown that AGEs content increases within a few weeks after the animals were rendered diabetic and that this increase was systemic, occurring in the kidneys, skin, and vascular tissue.…”

Section: Effects Of Hg On Expression Of Rage: Inhibition Of Flavonoidsmentioning

confidence: 97%

Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory cytokines in human monocytic THP‐1 cells

Huang

et al. 2009

Molecular Nutrition Food Res

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Activation of circulating monocytes by hyperglycemia is bound to play a role in inflammatory and atherosclerosis. In this study, we examined whether flavonoids (catechin, EGCG, luteolin, quercetin, rutin) - phytochemicals that may possible belong to a new class of advanced glycation end products (AGEs) inhibitors - can attenuate high glucose (15 mmol/L, HG)-induced inflammation in human monocytes. Our results show that all flavonoids significantly inhibited HG-induced expression of proinflammatory genes and proteins, including TNF-alpha, interleukin-1beta (IL-1beta), and cyclooxygenase (COX)-2, at a concentration of 20 microM. Flavonoids also prevented oxidative stress in activated monocytes, as demonstrated by their inhibitory effects on intracellular reactive oxygen species (ROS) and N(epsilon)-(carboxymethyl)lysine formation caused by HG. These inhibitory effects may involve inhibition of nuclear factor-kappaB activation and may be supported by downregulation of the following: i) PKC-dependent NADPH oxidase pathway; ii) phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase, and iii) mRNA expression of receptor of AGEs. In addition, we found for the first time that lower levels of Bcl-2 protein under HG conditions could be countered by the action of flavonoids. Our data suggest that, along with their antioxidant activities, flavonoids possess anti-inflammatory properties and might therefore have additional protective effects against glycotoxin-related inflammation.

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“…Leukocytes in diabetic patients may be activated by advanced end products or reactive oxygen radicals or cytokines (14)(15)(16). Activated leukocytes secrete many kinds of cytokines and transcription factors having a crucial role in inflammation and thereby contribute to glomerulosclerosis (13,17).…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Neutrophil/Lymphocyte Ratio and Albuminuria in Diabetic Patients

Ünal¹,

Koçyiğit²,

I³

et al. 2015

Turk Neph Dial Transpl

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OBJectIVe: We aimed to investigate whether there is a relationship between neutrophil/lymphocyte (N/L) ratio and albuminuria in diabetic patients. MAterIAl and MetHODS:This study included 170 diabetic patients. The patients were divided 3 groups according to urinary albumin creatinine ratio (UACR). The first group included patients with normoalbuminuria (UACR <0.030). The second group included patients with moderately increased albuminuria (0.030-0.300), whereas the third group consisted of patients with severely increased albuminuria (UACR>0.300).reSultS: N/L ratio was 1.83, 2.23, and 2.77 in first, second, and third group, respectively. It was meaningfully higher in third group when compared with two groups. Although there was no statistically meaningful difference between the first group and the second group, it was higher in the second group than that in the first group. The hemoglobin concentration was 14.3 ±1.6 g/dl, 13.6 ± 1.8 g/dl, and 12.4 ± 1.8 g/dl in the first, second, and third group, respectively. It was significantly lower in the third group when compared with other groups. However, there was no meaningful difference between the first group and the second group. Presence of anemia increased step-wise from the first group to the third group (8.7%, 21.3%, and 48.1%, respectively).cOncluSIOn: N/L ratio and anemia associate closely with albuminuria in diabetic patients.

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Advanced glycation end products upregulate angiogenic and pro-inflammatory cytokine production in human monocyte/macrophages

Cited by 80 publications

References 51 publications

Endothelial Dysfunction in Patients with Chronic Kidney Disease Results from Advanced Glycation End Products (AGE)-Mediated Inhibition of Endothelial Nitric Oxide Synthase through RAGE Activation

Endothelial Dysfunction in Patients with Chronic Kidney Disease Results from Advanced Glycation End Products (AGE)-Mediated Inhibition of Endothelial Nitric Oxide Synthase through RAGE Activation

Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory cytokines in human monocytic THP‐1 cells

Relationship Between Neutrophil/Lymphocyte Ratio and Albuminuria in Diabetic Patients

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