Introduction
Statins are known to lower CRP, and this reduction has been suggested to contribute to the established efficacy of these drugs in reducing cardiovascular events and outcomes. However, the exact mechanism underlying the CRP-lowering effect of statins remains elusive.

Material and methods
In order to test the possibility of direct interaction, we performed an in silico study by testing the orientation of the respective ligands (statins) and phosphorylcholine (the standard ligand of CRP) in the CRP active site using Molecular Operating Environment (MOE) software.

Results
Docking experiments showed that all statins could directly interact with CRP. Among statins, rosuvastatin had the strongest interaction with CRP (pKi = 16.14), followed by fluvastatin (pKi = 15.58), pitavastatin (pKi = 15.26), atorvastatin (pKi = 14.68), pravastatin (pKi = 13.95), simvastatin (pKi = 7.98) and lovastatin (pKi = 7.10). According to the above-mentioned results, rosuvastatin, fluvastatin, pitavastatin and atorvastatin were found to have stronger binding to CRP compared with the standard ligand phosphocholine (pKi = 14.55).

Conclusions
This finding suggests a new mechanism of interaction between statins and CRP that could be independent of the putative cholesterol-lowering activity of statins.



中文翻译：

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他汀类药物和 C 反应蛋白：直接相互作用的计算机证据

引言
众所周知，他汀类药物可以降低 CRP，并且这种降低被认为有助于这些药物在减少心血管事件和结果方面的既定功效。然而，他汀类药物降低 CRP 作用的确切机制仍然难以捉摸。

材料和方法
为了测试直接相互作用的可能性，我们通过使用分子操作环境 (MOE) 测试 CRP 活性位点中相应配体（他汀类药物）和磷酸胆碱（CRP 的标准配体）的方向进行了计算机研究） 软件。

结果
对接实验表明，所有他汀类药物均可与 CRP 直接相互作用。在他汀类药物中，瑞舒伐他汀与CRP的相互作用最强（pKi = 16.14），其次是氟伐他汀（pKi = 15.58）、匹伐他汀（pKi = 15.26）、阿托伐他汀（pKi = 14.68）、普伐他汀（pKi = 13.95）、辛伐他汀（pKi = 7.98) 和洛伐他汀 (pKi = 7.10)。根据上述结果，与标准配体磷酸胆碱相比，瑞舒伐他汀、氟伐他汀、匹伐他汀和阿托伐他汀与CRP的结合力更强（pKi = 14.55）。

结论
这一发现表明他汀类药物与 CRP 之间相互作用的新机制可能与他汀类药物的推定降胆固醇活性无关。