Receptor for advanced glycation end products (RAGE) and its inflammatory ligand EN-RAGE in non-diabetic subjects with pre-mature coronary artery disease

Objective: Inflammation participates in atherosclerosis from its inception onwards. RAGE (receptor for advanced glycation end products) and its natural pro-inflammatory ligand, EN-RAGE (extracellular newly identified RAGE-binding protein) have been implicated in various inflammatory diseases. In present study, we determined the expression of RAGE and EN-RAGE in peripheral blood mononuclear cells (PBMCs) of subjects with pre-mature coronary artery disease (CAD) for the first time. Methods and results: The study patients were angiographically proven non-diabetic patients with pre-mature CAD (Group I; N = 100) and control group comprised of subjects with coronary risk factors and without coronary artery lesions (Group II; N = 40). Semi-quantitative RT-PCR was performed to determine transcriptional expression of RAGE and EN-RAGE in PBMCs. Soluble RAGE (sRAGE) and C-reactive protein (hsCRP) levels were determined in serum of all study subjects using immunoassays. A significantly increased transcriptional expression of RAGE and EN-RAGE in PBMCs (p < 0.01) of Group I patients was observed. Increased circulating hsCRP (p < 0.01) levels and decreased sRAGE (p < 0.01) levels were observed in Group I as compared with the Group II subjects. Severity of disease determined by Gensini score was found to be positively correlated with transcriptional expression of RAGE (r = 0.530) and EN-RAGE (r = 0.323). EN-RAGE expression revealed a strong association with RAGE (r = 0.326), hsCRP (r = 0.251) and a negative association with sRAGE (r = -0.222). Conclusions: Increased expression of RAGE and EN-RAGE in non-diabetic pre-mature CAD and various associations discussed may amplify several cellular perturbations and thus significantly contribute to the pathophysiology of CAD.