Atherosclerosis-related functions of C-reactive protein.
Atherosclerosis-related functions of C-reactive protein.
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DOI：
10.2174/187152910793743841
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发表时间：
2010-12-01
期刊：
影响因子：
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通讯作者：
Singh SK
中科院分区：
文献类型：
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作者：
Agrawal A;Hammond DJ Jr;Singh SK
C-反应蛋白(CRP)是由肝细胞分泌的由相同单体组成的五聚体分子，以五聚体形式在血浆中循环，定位于动脉粥样硬化病变。在某些情况下，通过使用不与天然五聚体CRP反应但对分离的单体CRP具有特异性的单抗来检测定位的CRP。据报道，一旦CRP与某些配体结合，CRP的五聚体结构就会改变，从而可以解离成单体。因此，在动脉粥样硬化病变中发现的单体C反应蛋白可能是固定的、配体结合的、C反应蛋白配体结合功能的副产物。CRP与修饰形式的低密度脂蛋白(LDL)结合。C反应蛋白与氧化低密度脂蛋白的结合需要酸性的pH条件；在生理pH下的结合是有争议的。C反应蛋白与酶修饰的低密度脂蛋白的结合在生理pH时发生，但在酸性pH时结合增强。使用酶修饰的低密度脂蛋白，CRP已被证明可以防止酶修饰的低密度脂蛋白负载的巨噬细胞泡沫细胞的形成。在ApoE−/−和ApoB100/100Ldlr−/−小鼠动脉粥样硬化模型中，C反应蛋白既不促进动脉粥样硬化，也不具有动脉粥样硬化保护作用，但在一项研究中发现，在ApoB100/100Ldlr−/−小鼠中，C反应蛋白具有轻微的动脉粥样硬化保护作用。人类C反应蛋白在小鼠动脉粥样硬化模型中无效的原因尚未确定。在动脉粥样硬化的发展过程中，可能需要一个炎症环境，如以酸性pH为特征的环境，以使CRP和致动脉粥样硬化的低密度脂蛋白有效地相互作用，并在动物模型中观察CRP可能的动脉粥样硬化保护作用。
C-reactive protein (CRP) is secreted by hepatocytes as a pentameric molecule made up of identical monomers, circulates in the plasma as pentamers, and localizes in atherosclerotic lesions. In some cases, localized CRP was detected by using monoclonal antibodies that did not react with native pentameric CRP but were specific for isolated monomeric CRP. It has been reported that, once CRP is bound to certain ligands, the pentameric structure of CRP is altered so that it can dissociate into monomers. Accordingly, the monomeric CRP found in atherosclerotic lesions may be a stationary, ligand-bound, by-product of a ligand-binding function of CRP. CRP binds to modified forms of low-density lipoprotein (LDL). The binding of CRP to oxidized LDL requires acidic pH conditions; the binding at physiological pH is controversial. The binding of CRP to enzymatically-modified LDL occurs at physiological pH; however, the binding is enhanced at acidic pH. Using enzymatically-modified LDL, CRP has been shown to prevent the formation of enzymatically-modified LDL-loaded macrophage foam cells. CRP is neither pro-atherogenic nor atheroprotective in ApoE−/− and ApoB100/100Ldlr −/− murine models of atherosclerosis, except in one study where CRP was found to be slightly atheroprotective in ApoB100/100Ldlr −/− mice. The reasons for the ineffectiveness of human CRP in murine models of atherosclerosis are not defined. It is possible that an inflammatory environment, such as those characterized by acidic pH, is needed for efficient interaction between CRP and atherogenic LDL during the development of atherosclerosis and to observe the possible atheroprotective function of CRP in animal models.