Singh Sanjay K, Suresh Madathilparambil V, Prayther Deborah C, Moorman Jonathan P, Rusiñol Antonio E, Agrawal Alok
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Clin Chim Acta. 2008 Aug;394(1-2):94-8. doi: 10.1016/j.cca.2008.04.015. Epub 2008 Apr 27.
C-reactive protein (CRP) is an acute phase plasma protein. An important binding specificity of CRP is for the modified forms of low-density lipoprotein (LDL) in which the phosphocholine-binding sites of CRP participate. CRP, however, does not bind to native LDL.
We investigated the interaction of CRP with native LDL using sucrose density gradient ultracentrifugation.
We found that the blocking of the phosphocholine-binding sites of CRP with phosphoethanolamine (PEt) converted CRP into a potent molecule for binding to native LDL. In the presence of PEt, CRP acquired the ability to bind to fluid-phase purified native LDL. Because purified native LDL may undergo subtle modifications, we also used whole human serum as the source of native LDL. In the presence of PEt, CRP bound to native LDL in serum also. The effect of PEt on CRP was selective for LDL because PEt-complexed CRP did not bind to high-density lipoprotein in the serum.
The pharmacologic intervention of endogenous CRP by PEt-based compounds, or the use of exogenously prepared CRP-PEt complexes, may turn out to be an effective approach to capture native LDL cholesterol in vivo to prevent the development of atherosclerosis.
C反应蛋白（CRP）是一种急性期血浆蛋白。CRP的一个重要结合特异性是针对低密度脂蛋白（LDL）的修饰形式，其中CRP的磷酸胆碱结合位点参与其中。然而，CRP不与天然LDL结合。
我们使用蔗糖密度梯度超速离心法研究了CRP与天然LDL的相互作用。
我们发现用磷酸乙醇胺（PEt）阻断CRP的磷酸胆碱结合位点可将CRP转化为一种能与天然LDL结合的有效分子。在PEt存在的情况下，CRP获得了与液相纯化的天然LDL结合的能力。由于纯化的天然LDL可能会发生细微修饰，我们还使用全人血清作为天然LDL的来源。在PEt存在的情况下，CRP也能与血清中的天然LDL结合。PEt对CRP的作用对LDL具有选择性，因为PEt复合的CRP不与血清中的高密度脂蛋白结合。
基于PEt的化合物对内源性CRP的药理干预，或使用外源性制备的CRP-PEt复合物，可能会成为一种在体内捕获天然LDL胆固醇以预防动脉粥样硬化发展的有效方法。
