The receptor RAGE as a progression factor amplifying arachidonate-dependent inflammatory and proteolytic response in human atherosclerotic plaques - Role of glycemic control
The receptor RAGE as a progression factor amplifying arachidonate-dependent inflammatory and proteolytic response in human atherosclerotic plaques - Role of glycemic control
复制标题
DOI：
10.1161/01.cir.0000086014.80477.0d
复制
发表时间：
2003-09-02
期刊：
影响因子：
37.8
通讯作者：
Mezzetti, A
中科院分区：
文献类型：
--
作者：
Cipollone, F;Iezzi, A;Mezzetti, A
背景-糖基化终产物受体（receptor for advanced glycation end products，AGEs）在糖尿病动脉粥样硬化中起重要作用。最近，我们已经证明了环氧合酶-2和PGE合酶-1（考克斯-2/mPGES-1）在人类症状性斑块中的表达增强，并提供了证据表明它与金属蛋白酶（MMP）诱导的斑块破裂有关。然而，影响斑块考克斯-2/mPGES-1表达的特异性跨膜信号通路尚不清楚。本研究的目的是表征人斑块中的p53表达，并将其与炎症浸润，考克斯-2/mPGES-1和MMP表达，并与临床证据diabetes.Methods和Results-Plaques从60例接受颈动脉内膜切除术的患者分为糖尿病和非糖尿病根据2型糖尿病的临床证据。通过免疫组化和Western blot分析斑块中TNF-α、NF-κ B、考克斯-2/mPGES-1、MMP-2和MMP-9、脂质和氧化低密度脂蛋白（oxLDL）含量以及胶原含量，而酶谱法检测MMP活性。免疫组织化学用于鉴定CD 68+巨噬细胞、CD 3 + T淋巴细胞、平滑肌细胞（SMC）和HLA-DR+炎性细胞。糖尿病斑块的发生率高于对照组（P
Background-RAGE (receptor for advanced glycation end products [AGEs]) plays a role in diabetic atherosclerosis. Recently, we have demonstrated enhanced expression of cyclooxygenase-2 and PGE synthase-1 (COX-2/mPGES-1) in human symptomatic plaques, and provided evidence that it is associated with metalloproteinase (MMP)-induced plaque rupture. However, the specific transmembrane signaling pathway(s) influencing plaque COX-2/mPGES-1 expression is unknown. The aim of this study was to characterize RAGE expression in human plaques and to correlate it with the inflammatory infiltration, COX-2/mPGES-1 and MMP expression, and with clinical evidence of diabetes.Methods and Results-Plaques obtained from 60 patients undergoing carotid endarterectomy were divided into diabetic and nondiabetic according to clinical evidence of type 2 diabetes. Plaques were subjected to analysis of RAGE, NF-kappaB, COX-2/mPGES-1, MMP-2 and MMP-9, lipid and oxidized LDL (oxLDL) content, and collagen content by immunohistochemistry and Western blot, whereas zymography was used to detect MMP activity. Immunohistochemistry was used to identify CD68+ macrophages, CD3+ T-lymphocytes, smooth muscle cells (SMCs), and HLA-DR+ inflammatory cells. Diabetic plaques had more (P