Modulation of high sensitivity C-reactive protein by soluble receptor for advanced glycation end products

Abstract

High sensitivity C-reactive protein (hs-CRP) is synthesized mainly by hepatocytes in response to tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6). The interaction of advanced glycation end products (AGEs) with the receptor for advanced glycation end products (RAGE) increases the expression of the cytokines TNF-alpha, IL-1, and IL-6. Soluble receptor for advanced glycation end products (sRAGE) competes with RAGE for binding with AGEs. Hence, low sRAGE levels may increase interaction of AGEs with RAGE resulting in the increased production of cytokines. It is hypothesized that serum levels of sRAGE modulate serum levels of hs-CRP. The objectives are to determine if (i) serum levels of sRAGE are lower and those of TNF-alpha and hs-CRP are higher in non-ST-segment elevation myocardial infarction (NSTEMI) patients compared to control subjects; (ii) serum levels of TNF-alpha and hs-CRP are positively correlated; and (iii) sRAGE is negatively correlated with hs-CRP and TNF-alpha. The study consisted of 36 patients with NSTEMI and 30 age-matched healthy male subjects. Serum levels of sRAGE and TNF-alpha were determined by enzyme-linked immunoassay and hs-CRP was measured using near infrared immunoassay. Serum levels of sRAGE were lower, while those of TNF-alpha and hs-CRP were higher in patients with NSTEMI compared to controls. The levels of sRAGE were negatively correlated with those of TNF-alpha and hs-CRP, while TNF-alpha was positively correlated with hs-CRP in both the control subjects and NSTEMI patients. The data suggest that sRAGE modulates the synthesis of hs-CRP through TNF-alpha.

Relationship between sRAGE and hsCRP as Markers of Cardiovascular Disease Risk Factors in Diabetic and Non-Diabetic Men with Central Obesity

“…12 Similar to this study, in both HbA1c <6.5% and ≥6.5% groups of current study, there was a negative correlation between sRAGE and hsCRP. Previous studies have documented inverse correlations between sRAGE with CRP 13 and low levels of sRAGE among persons with coronary heart disease 14 . sRAGE can serve as a 'bait' receptor to catch ligand and able to inhibit the cellular signaling.…”

Effects of Exercise on sRAGE Levels and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized Controlled Trial

“…Interaction of AGE with RAGE leads to increased expressions of inflammatory cytokines such as TNF-␣, IL-1, and IL-6 through nuclear factor-B (23). Moreover, a recent study has shown that sRAGE modulates the synthesis of CRP (24). An et al (25) reported that circulating sRAGE has a significant negative association with hsCRP in patients with type 2 diabetes.…”

Increased Levels of Calprotectin in Obesity Are Related to Macrophage Content: Impact on Inflammation and Effect of Weight Loss

“…Interestingly, serum sRAGE levels in rheumatoid arthritis patients were negatively associated with serum levels of CRP (51). It was also recently described that increased serum CRP together with reduced concentrations of sRAGE appear to be due to elevated TNF-α levels (52). In Il10 null mice, a murine model of colitis, no inflammation in rectosigmoid colon and a decrease in circulating concentrations of TNF-α were observed after treatment with sRAGE (53).…”