LOW SERUM LEVELS OF SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IS NOT AN UNIVERSAL BIOMARKER FOR CARDIOVASCULAR DISEASE
Kailash Prasad, M.D., Ph.D., University of Saskatchewan, Saskatoon, SK, Canada
Interaction of advanced glycation end products (AGEs) are heterogeneous group of irreversible adducts formed from non-enzymatic glycation of proteins, nucleic acid, and lipids with reducing sugars. Interaction of AGEs with its cell-bound receptor RAGE (receptor for AGEs) increases the expression of inflammatory mediators and generation of oxygen radicals and activates nuclear factor kappa-B which have adverse effects. Circulating soluble receptor for AGEs (sRAGE) acts as decoy for RAGE by binding with RAGE ligands, AGEs, and has protective effects against delirious effects of interaction of AGEs with RAGE. Serum levels sRAGE are low in patients with coronary artery disease, heart failure, essential hypertension, hypercholesterolemia and Alzeihmer’s disease. Based on these findings, low levels of serum has been suggested to be a biomarker of the disease. However, we and others have shown that serum levels of sRAGE are high in diabetes and chronic kidney disease. Hence low levels sRAGE as a disease biomarker would not apply for these two conditions. Considering these observations, and involvement of AGEs ,sRAGE and RAGE in AGE-RAGE –mediated disease, I proposed that the ratio of AGEs/sRAGE should be considered as universal biomarker/risk marker of the disease. We have demonstrated that the serum levels of both AGEs and sRAGE are elevated in diabetes and chronic kidney disease, the increase being more in AGEs than sRAGE. In patients with end stage renal disease, we have reported that the levels of AGES and sRAGE were respectively 6.77 times and 2.45 times higher than in healthy control subjects. WE also reported that the ratio of AGEs/sRAGE are elevated in patients with coronary artery disease. In conclusion, the elevated ratio of AGEs/ sRAGE, but not the low serum levels of sRAGE, is an universal biomarker for disease states.