单位：[1]Cardiovascular Center/Division of Cardiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Beijing City 100053, China 临床科室心血管中心心内科首都医科大学附属北京友谊医院[2]Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian City 116011, China 大连医科大学附属第一医院[3]College of Life Sciences and Pharmacy, Dalian University of Technology, Dalian City 116027, China [4]Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian City 116044, China
Background. Circulating monocytes play a critical role in the pathogenesis of atherosclerosis. Monocyte homing to sites of atherosclerosis is primarily initiated by selectin. Thus, blockade of the interaction of selectins and their ligands holds a significant role in monocyte homing which might be a potential approach to treat atherosclerosis. Here, we investigated the efficacy of a novel peptide analogue of selectin ligands IELLQAR in atherosclerosis. Methods and Results. In this study, we firstly measured the effect of the IELLQAR selectin-binding peptide on the inhibition of binding of selectins to monocytes by flow cytometry, which exhibited a dose-dependent inhibitory effect on the binding of the P-, E-, and L-selectins to monocytes, especially the inhibition of P-selectin binding to human peripheral blood monocytes (PBMCs) (half maximal inhibitory concentration (IC50 5 M)) and THP-1 cells (IC(50)10 M). Furthermore, IELLQAR inhibited P-selectin-induced activation of CD11b on the surface of monocytes and decreased adhesion of monocytes to the endothelium. ApoE(-/-) mice with or without IELLQAR (1 or 3 mg/kg) fed a Western-type diet (WTD) or which had disturbed blood flow-induced shear stress underwent partial left carotid artery ligation (PLCA) to induce atherosclerosis. In the WTD- and PLCA-induced atherosclerosis models, atherosclerotic plaque formation and monocyte/macrophage infiltration of the arterial wall both decreased in ApoE(-/-) mice treated with the IELLQAR peptide. Our results also revealed that IELLQAR inhibited the differentiation of monocytes into macrophages through P-selectin-dependent activation of the nuclear factor- (NF-) B and mammalian target of rapamycin (mTOR) pathways. Conclusion. Collectively, our results demonstrated that IELLQAR, a peptide analogue of selectin ligands, inhibited selectin binding to monocytes, which led to subsequent attenuation of atherosclerosis via inhibition of monocyte activation. Hence, use of the IELLQAR peptide provides a new approach and represents a promising candidate for the treatment of atherosclerosis in the early stage of disease.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770340, 81100220, 81700245]; Natural Science Foundation of Liaoning ProvinceNatural Science Foundation of Liaoning Province [2015020295, LQ2017020]
第一作者单位：[1]Cardiovascular Center/Division of Cardiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Beijing City 100053, China [2]Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian City 116011, China
通讯作者：
推荐引用方式(GB/T 7714)：
Ye Zhishuai,Zhang Shanfeng,Liu Yubo,et al.A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation[J].MEDIATORS of INFLAMMATION.2019,2019:doi:10.1155/2019/8709583.
APA：
Ye, Zhishuai,Zhang, Shanfeng,Liu, Yubo,Wang, Shujing,Zhang, Jianing&Huang, Rongchong.(2019).A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation.MEDIATORS of INFLAMMATION,2019,
MLA：
Ye, Zhishuai,et al."A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation".MEDIATORS of INFLAMMATION 2019.(2019)
