Abstract
High sensitivity C-reactive protein (hs-CRP) is synthesized mainly by hepatocytes in response to tumor necrosis factor-alpha (TNF-α), 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-α, 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-α and hs-CRP are higher in non-ST-segment elevation myocardial infarction (NSTEMI) patients compared to control subjects; (ii) serum levels of TNF-α and hs-CRP are positively correlated; and (iii) sRAGE is negatively correlated with hs-CRP and TNF-α. The study consisted of 36 patients with NSTEMI and 30 age-matched healthy male subjects. Serum levels of sRAGE and TNF-α 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-α and hs-CRP were higher in patients with NSTEMI compared to controls. The levels of sRAGE were negatively correlated with those of TNF-α and hs-CRP, while TNF-α 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-α.
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Acknowledgments
This manuscript forms part of the PhD thesis of Dr. Erick D. McNair. This work was supported by grants from the Heart and Stroke Foundation of Saskatchewan and the Pollack Research Foundation of Saskatchewan. The authors acknowledge the assistance of Ms. Heather Neufeld in biochemical measurements and Ms. Barbara Raney with the preparation of this manuscript.
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McNair, E.D., Wells, C.R., Mabood Qureshi, A. et al. Modulation of high sensitivity C-reactive protein by soluble receptor for advanced glycation end products. Mol Cell Biochem 341, 135–138 (2010). https://doi.org/10.1007/s11010-010-0444-3
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DOI: https://doi.org/10.1007/s11010-010-0444-3