A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation
Joint Authors
Huang, Rongchong
Ye, Zhishuai
Zhang, Shanfeng
Liu, Yubo
Wang, Shujing
Zhang, Jianing
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-06
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
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 μM)) and THP-1 cells (IC50~10 μM).
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-) κB 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.
American Psychological Association (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،Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1193557
Modern Language Association (MLA)
Ye, Zhishuai…[et al.]. A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation. Mediators of Inflammation No. 2019 (2019), pp.1-15.
https://search.emarefa.net/detail/BIM-1193557
American Medical Association (AMA)
Ye, Zhishuai& Zhang, Shanfeng& Liu, Yubo& Wang, Shujing& Zhang, Jianing& Huang, Rongchong. A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-15.
https://search.emarefa.net/detail/BIM-1193557
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1193557