A novel peptide inhibitor attenuates C-reactive protein's pro-inflammatory effects in-vivo.
A novel peptide inhibitor attenuates C-reactive protein's pro-inflammatory effects in-vivo.
复制标题
一种新型肽抑制剂可减弱 C 反应蛋白的体内促炎作用。
DOI：
10.1016/j.ijcard.2013.06.047
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发表时间：
2013
影响因子：
3.5
通讯作者：
Kumaresan,PR
中科院分区：
文献类型：
--
作者：
Jialal,I;Devaraj,S;Smith,G;Lam,KS;Kumaresan,PR
研究背景急性冠状动脉综合征患者C反应蛋白（CRP）水平升高可预测心血管事件，也预示预后不良。Muchin-vitroandin-vivodata支持CRP在atherogenesis.MethodsUsing的一珠一化合物（OBOC）组合库方法的作用，我们已经成功地确定了对人类CRP的肽，抑制其生物学效应在体外。因此，我们测试了最好的特征抑制剂（CRP-i2）的影响，CRP在适当的动物模型，Wistar rats.ResultsTreatment与CRP的影响，导致显着增加超氧阴离子，核因子κ B（NFκB）的活性和释放的炎症生物标志物从巨噬细胞相比，Wistar大鼠与人白蛋白（HuSA）治疗。用抑制剂CRP-12预处理导致CRP诱导的超氧阴离子、NFκB活性和炎症生物标志物显著降低。此外，没有观察到临床或实验室相关的不良反应。ConclusionsWe表明，我们的新的肽抑制剂衰减CRPin体内的促炎作用。未来的研究将检查这种抑制剂对血管病理学的长期影响。
BackgroundHigher levels of C-reactive protein (CRP) predict cardiovascular events and also portend a poorer prognosis in patients with acute coronary syndromes. Muchin-vitroandin-vivodata support a role for CRP in atherogenesis.MethodsUsing the one-bead-one-compound (OBOC) combinatorial library method we have successfully identified peptides against human CRP that inhibit its biological effectsin-vitro. Hence we tested the effect of the best characterized inhibitor (CRP-i2) on the effects of CRP in an appropriate animal model, Wistar rats.ResultsTreatment with CRP resulted in significant increase in superoxide anion, nuclear factor kappaB (NFκb) activity and the release of biomarkers of inflammation from macrophages compared to Wistar rats treated with human albumin (HuSA). Pre-treatment with the inhibitor, CRP-i2, resulted in a significant reduction in CRP induced superoxide anion, NFκb activity and biomarkers of inflammation. Also, there were no observed clinical or laboratory related adverse effects.ConclusionsWe demonstrate that our novel peptide inhibitor attenuates the proinflammatory effects of CRPin-vivo. Future studies will examine the long-term effects of this inhibitor on vascular pathobiology.