Department of Pathology, College of Medicine, University of Saskatchewan and Royal University Hospital, Saskatoon, SK, Canada.
Mol Cell Biochem. 2010 Aug;341(1-2):135-8. doi: 10.1007/s11010-010-0444-3. Epub 2010 Mar 27.
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.
高敏 C 反应蛋白（hs-CRP）主要由肝细胞在肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）和白细胞介素-6（IL-6）的刺激下合成。晚期糖基化终产物（AGEs）与晚期糖基化终产物受体（RAGE）的相互作用增加了 TNF-α、IL-1 和 IL-6 等细胞因子的表达。可溶性晚期糖基化终产物受体（sRAGE）与 RAGE 竞争结合 AGEs。因此，低水平的 sRAGE 可能会增加 AGEs 与 RAGE 的相互作用，从而导致细胞因子的产生增加。推测血清 sRAGE 水平调节 hs-CRP 水平。目的是确定（i）非 ST 段抬高型心肌梗死（NSTEMI）患者的血清 sRAGE 水平是否低于对照组，而 TNF-α和 hs-CRP 水平是否高于对照组；（ii）血清 TNF-α和 hs-CRP 水平是否呈正相关；（iii）sRAGE 是否与 hs-CRP 和 TNF-α呈负相关。该研究纳入了 36 例 NSTEMI 患者和 30 名年龄匹配的健康男性对照。采用酶联免疫吸附法测定血清 sRAGE 和 TNF-α水平，采用近红外免疫法测定 hs-CRP 水平。与对照组相比，NSTEMI 患者的血清 sRAGE 水平较低，而 TNF-α和 hs-CRP 水平较高。sRAGE 水平与 TNF-α和 hs-CRP 水平呈负相关，而 TNF-α与 hs-CRP 在对照组和 NSTEMI 患者中均呈正相关。研究数据表明，sRAGE 通过 TNF-α调节 hs-CRP 的合成。
