Agrawal Alok, Hammond David J, Singh Sanjay K
Department of Pharmacology, East Tennessee State University, Johnson City, TN 37614, USA.
Cardiovasc Hematol Disord Drug Targets. 2010 Dec 1;10(4):235-40. doi: 10.2174/187152910793743841.
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.
C反应蛋白（CRP）由肝细胞分泌，是一种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，并定位于动脉粥样硬化病变处。在某些情况下，使用单克隆抗体检测到局部CRP，这些抗体不与天然五聚体CRP反应，但对分离的单体CRP具有特异性。据报道，一旦CRP与某些配体结合，CRP的五聚体结构就会改变，从而解离成单体。因此，在动脉粥样硬化病变中发现的单体CRP可能是CRP配体结合功能的一种固定的、与配体结合的副产物。CRP与低密度脂蛋白（LDL）的修饰形式结合。CRP与氧化型LDL的结合需要酸性pH条件；在生理pH下的结合存在争议。CRP与酶修饰型LDL的结合发生在生理pH下；然而，在酸性pH下结合会增强。使用酶修饰型LDL已证明，CRP可防止酶修饰型LDL负载的巨噬细胞泡沫细胞的形成。在载脂蛋白E基因敲除（ApoE⁻/⁻）和载脂蛋白B100基因敲除/低密度脂蛋白受体基因敲除（ApoB¹⁰⁰/¹⁰⁰Ldlr⁻/⁻）的动脉粥样硬化小鼠模型中，CRP既不是促动脉粥样硬化的，也不是抗动脉粥样硬化的，只有一项研究发现CRP在ApoB¹⁰⁰/¹⁰⁰Ldlr⁻/⁻小鼠中具有轻微的抗动脉粥样硬化作用。人类CRP在动脉粥样硬化小鼠模型中无效的原因尚不清楚。在动脉粥样硬化发展过程中，可能需要一种炎症环境，如以酸性pH为特征的环境，以便CRP与致动脉粥样硬化的LDL之间进行有效相互作用，并观察CRP在动物模型中可能的抗动脉粥样硬化功能。
