A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation
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...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/8709583 |
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| author | Zhishuai Ye Shanfeng Zhang Yubo Liu Shujing Wang Jianing Zhang Rongchong Huang |
| author_facet | Zhishuai Ye Shanfeng Zhang Yubo Liu Shujing Wang Jianing Zhang Rongchong Huang |
| author_sort | Zhishuai Ye |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3dd3c87cccd94d6ea4303e587552fe11 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-3dd3c87cccd94d6ea4303e587552fe112025-02-03T06:08:10ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/87095838709583A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte ActivationZhishuai Ye0Shanfeng Zhang1Yubo Liu2Shujing Wang3Jianing Zhang4Rongchong Huang5Cardiovascular Center/Division of Cardiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Beijing City 100053, ChinaDepartment of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian City 116011, ChinaCollege of Life Sciences and Pharmacy, Dalian University of Technology, Dalian City 116027, ChinaDepartment of Biochemistry and Molecular Biology, Dalian Medical University, Dalian City 116044, ChinaCollege of Life Sciences and Pharmacy, Dalian University of Technology, Dalian City 116027, ChinaCardiovascular Center/Division of Cardiology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Beijing City 100053, ChinaBackground. 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.http://dx.doi.org/10.1155/2019/8709583 |
| spellingShingle | Zhishuai Ye Shanfeng Zhang Yubo Liu Shujing Wang Jianing Zhang Rongchong Huang A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation Mediators of Inflammation |
| title | A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation |
| title_full | A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation |
| title_fullStr | A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation |
| title_full_unstemmed | A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation |
| title_short | A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation |
| title_sort | peptide analogue of selectin ligands attenuated atherosclerosis by inhibiting monocyte activation |
| url | http://dx.doi.org/10.1155/2019/8709583 |
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