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Title: Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation
Authors: Dutta, Bamaprasad
Park, Jung Eun
Kumar, Subodh
Hao, Piliang
Gallart-Palau, Xavier
Serra, Aida
Ren, Yan
Sorokin, Vitaly
Lee, Chuen Neng
Ho, Hee Hwa
de Kleijn, Dominique
Sze, Siu Kwan
Keywords: DRNTU::Science::Biological sciences
Protein Deamidation
Monocyte Adhesion
Issue Date: 2017
Source: Dutta, B., Park, J. E., Kumar, S., Hao, P., Gallart-Palau, X., Serra, A., . . . Sze, S. K. (2017). Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation. Scientific Reports, 7, 5765-. doi:10.1038/s41598-017-06202-2
Series/Report no.: Scientific Reports
Abstract: Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls and constitutes a major component of vascular disease pathology, but the molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation of asparagine to generate isoDGR structures that bind to integrin αvβ3 on circulating leukocytes. Here we report the identification of isoDGR motifs in human atherosclerotic plaque components including extracellular matrix (ECM) proteins fibronectin and tenascin C, which have been strongly implicated in human atherosclerosis. We further demonstrate that deamidation of NGR motifs in fibronectin and tenascin C leads to increased adhesion of the monocytic cell line U937 and enhanced binding of primary human monocytes, except in the presence of a αvβ3-blocking antibody or the αv-selective inhibitor cilengitide. In contrast, under the same deamidating conditions monocyte-macrophages displayed only weak binding to the alternative ECM component vitronectin which lacks NGR motifs. Together, these findings confirm a critical role for isoDGR motifs in mediating leukocyte adhesion to the ECM via integrin αvβ3 and suggest that protein deamidation may promote the pathological progression of human atherosclerosis by enhancing monocyte recruitment to developing plaques.
ISSN: 2045-2322
DOI: 10.1038/s41598-017-06202-2
Rights: © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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