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Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

  • Karly C. Sourris , Jasmine G. Lyons , Sonia L. Dougherty , Vibhasha Chand , Nora E. Straznicky , Markus P. Schlaich , Mariee T. Grima , Mark E. Cooper , Bronwyn A. Kingwell , Maximilian P.J. de Courten , Josephine M. Forbes and Barbora de Courten EMAIL logo
Published/Copyright: March 23, 2013
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 52 Issue 1

Abstract

Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals.

Methods: We measured body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carboxymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC).

Results: Plasma CML concentrations were related to diastolic blood pressure (r=−0.51, p<0.01) independently of age, sex, BMI and WHR (p<0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r=0.47, p<0.01) before and after adjustment for age, sex, BMI and WHR (p<0.05). Plasma CML concentrations were related to the pulse pressure before (r=0.42; p<0.05) and after adjustment for age, sex, BMI and waist (p<0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p=ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p=ns).

Conclusions: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.

Keywords: advanced glycation end products; alkaline phosphatase; blood pressure; central obesity; chronic low-grade inflammation; NF-κB activity
Corresponding author: A/Prof. Barbora de Courten, MD, PhD, MPH, FRACP, Baker IDI Heart and Diabetes Institute, 75 Commercial Rd, Melbourne, 3004, VIC, Australia, Phone: +61 3 85321353, Fax: +61 3 85321111, E-mail:

We wish to thank all volunteers for their participation in the study. This research was supported by Bennelong foundation, Cardiovascular lipid grant, National Health and Medical Research Council of Australia (NHMRC) and Diabetes Australia Research Trust Millennium Award and the Victorian Government’s Operational Infrastructure Support Program. BdC, JMF, BK, MEC, MS are all fellows of the NHMRC of Australia. KCS is supported by a Viertel Diabetes Australia Research Trust Fellowship. No sponsor had any role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2012-12-5
Accepted: 2013-2-14
Published Online: 2013-03-23
Published in Print: 2014-01-01

©2014 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2012-0850
Keywords for this article
advanced glycation end products; alkaline phosphatase; blood pressure; central obesity; chronic low-grade inflammation; NF-κB activity

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Editorial
  4. Frontiers in research on the Maillard reaction in aging and chronic disease
  5. Reviews
  6. Role of the Maillard reaction in aging and age-related diseases. Studies at the cellular-molecular level
  7. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review
  8. Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications
  9. Mini Reviews
  10. Post-translational modification derived products (PTMDPs): toxins in chronic diseases?
  11. Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes
  12. Augmentation of blood lipid glycation and lipid oxidation in diabetic patients
  13. Maillard reaction products: some considerations on their health effects
  14. The Maillard reaction and food allergies: is there a link?
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  16. Chelation therapy for the management of diabetic complications: a hypothesis and a proposal for clinical laboratory assessment of metal ion homeostasis in plasma
  17. Genetics and Molecular Diagnostics
  18. Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality
  19. General Clinical Chemistry and Laboratory Medicine
  20. Quantification of glyoxal, methylglyoxal and 3-deoxyglucosone in blood and plasma by ultra performance liquid chromatography tandem mass spectrometry: evaluation of blood specimen
  21. A new HPLC-based assay for the measurement of fructosamine-3-kinase (FN3K) and FN3K-related protein activity in human erythrocytes
  22. Increased circulating advanced glycation endproducts (AGEs) in acute trauma patients
  23. Circulating soluble RAGE increase after a cerebrovascular event
  24. Pentosidine determination in CSF: a potential biomarker of Alzheimer’s disease?
  25. Cardiovascular Diseases
  26. Skin autofluorescence as proxy of tissue AGE accumulation is dissociated from SCORE cardiovascular risk score, and remains so after 3 years
  27. Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure
  28. Total plasma Nε-(carboxymethyl)lysine and sRAGE levels are inversely associated with a number of metabolic syndrome risk factors in non-diabetic young-to-middle-aged medication-free subjects
  29. Translational Research Papers
  30. Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells
  31. Formation of nitri- and nitrosylhemoglobin in systems modeling the Maillard reaction
  32. Skin aging by glycation: lessons from the reconstructed skin model
  33. How to help the skin cope with glycoxidation
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