The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis Published, JLR Papers in Press, January 29, 2007.
The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis Published, JLR Papers in Press, January 29, 2007.
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DOI：
10.1194/jlr.m600414-jlr200
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发表时间：
2007-04
影响因子：
6.5
通讯作者：
M. Tabuchi;Katsumi Inoue;Hitomi Usui-Kataoka;Kazuko Kobayashi;Misako Teramoto;Koji Takasugi;K. Shikata;M. Yamamura;K. Ando;K. Nishida;Junko Kasahara;N. Kume;L. R. Lopez;K. Mitsudo;M. Nobuyoshi;T. Yasuda;T. Kita;H. Makino;E. Matsuura
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文献类型：
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作者：
M. Tabuchi;Katsumi Inoue;Hitomi Usui-Kataoka;Kazuko Kobayashi;Misako Teramoto;Koji Takasugi;K. Shikata;M. Yamamura;K. Ando;K. Nishida;Junko Kasahara;N. Kume;L. R. Lopez;K. Mitsudo;M. Nobuyoshi;T. Yasuda;T. Kita;H. Makino;E. Matsuura
C反应蛋白（CRP）是心血管疾病最强的独立预测因子之一。我们以前曾报道氧化低密度脂蛋白（oxLDL）与β2-糖蛋白I（β2GPI）相互作用，提示oxLDL/β2GPI复合物是自身免疫介导的动脉粥样硬化性血管疾病的假定自身抗原。本研究旨在探讨CRP与oxLDL/β2GPI复合物的相互作用及其与糖尿病患者动脉粥样硬化的关系。CRP/oxLDL/β2GPI复合物主要存在于糖尿病合并动脉粥样硬化患者血清中。相反，急性/慢性炎症患者的血清中存在非复合CRP亚型，即，各种致热性疾病、类风湿性关节炎（RA）和DM。免疫组化染色显示CRP、β2GPI和oxLDL在RA患者颈动脉斑块中共定位，但在滑膜组织中未发现，这强烈提示在动脉粥样硬化的发展过程中有复合物形成。血清CRP水平与可溶性细胞间粘附分子-1和血管细胞粘附分子-1相关，oxLDL/β2GPI复合物与总胆固醇和血红蛋白A1 c相关。因此，CRP/oxLDL/β2GPI复合物的产生似乎与动脉炎症、高血糖症和高胆固醇血症相关。CRP/oxLDL/β2GPI复合物可与热原性非复合CRP亚型区分开来，可能是动脉粥样硬化更特异和预测性的标志物。
C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with β2-glycoprotein I (β2GPI), implicating oxLDL/β2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/β2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/β2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and β2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/β2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/β2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/β2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.