Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Mar;23(1):11-6.
doi: 10.1055/s-0033-1363423.

Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: myth or reality

Kailash Prasad  1
Affiliations
Review

Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: myth or reality

Kailash Prasad. Int J Angiol. 2014 Mar.

Abstract

Advanced glycation end products (AGEs) interact with the receptor for AGEs (RAGE) on the membrane and induce deleterious effects via activation of nuclear factor kappa-B, and increased oxidative stress and inflammatory mediators. AGEs also combine with circulating soluble receptors (endogenous secretory RAGE [esRAGE] and soluble receptor for RAGE [sRAGE]) and sequester RAGE ligands and act as a cytoprotective agent. esRAGE is secreted from the cells and is a spliced variant of RAGE. The sRAGE on the other hand is proteolytically cleaved from cell surface receptor via matrix metalloproteinase (MMPs). sRAGE is elevated in type 1 and type 2 diabetes and in patients with decreased renal function. Serum levels of sRAGE are reduced in diseases including coronary artery disease, atherosclerosis, essential hypertension, chronic obstructive lung disease, heart failure, and hypercholesterolemia. Serum levels of AGEs are elevated in patients with coronary artery disease and atherosclerosis. However, the increases in serum AGEs are very high in patients with diabetes and renal disease. There is a positive correlation between serum levels of AGEs and RAGE and sRAGE. The elevated levels of sRAGE in patients with diabetes and impaired renal function may be due to increased levels of MMPs. AGEs increase in the expression and production of MMPs, which would increase the cleavage of sRAGE from cell surface. In conclusion, low level of serum sRAGE is a good biomarker for disease other than diabetes and renal disease. A unified formula that takes into consideration of AGEs, sRAGE, and esRAGE such as AGE/sRAGE or AGEs/esRAGE would be better biomarker than sRAGE or esRAGE for all AGE-RAGE-associated diseases including diabetes and renal disease.

Keywords: advanced glycation end products; biomarker; coronary artery disease; diabetes; endogenous secretory receptor for AGEs; renal dysfunction; soluble receptor for AGEs; unified biomarker for AGE-RAGE–associated diseases.

PubMed Disclaimer

References

    1. Takeuchi M, Yanase Y, Matsuura N. et al.Immunological detection of a novel advanced glycation end-product. Mol Med. 2001;7(11):783–791. - PMC - PubMed
    1. Thorpe S R, Baynes J W. Maillard reaction products in tissue proteins: new products and new perspectives. Amino Acids. 2003;25(3–4):275–281. - PubMed
    1. Bierhaus A, Hofmann M A, Ziegler R, Nawroth P P. AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept. Cardiovasc Res. 1998;37(3):586–600. - PubMed
    1. Prasad K. Soluble receptor for advanced glycation end products (sRAGE) and cardiovascular disease. Int J Angiol. 2006;15:57–68.
    1. Neeper M, Schmidt A M, Brett J. et al.Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem. 1992;267(21):14998–15004. - PubMed