Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation

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...

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Autores principales:	Bamaprasad Dutta, Jung Eun Park, Subodh Kumar, Piliang Hao, Xavier Gallart-Palau, Aida Serra, Yan Ren, Vitaly Sorokin, Chuen Neng Lee, Hee Hwa Ho, Dominique de Kleijn, Siu Kwan Sze
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8ed2a39083f4ac783ecce40423ac6b2
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spelling	oai:doaj.org-article:c8ed2a39083f4ac783ecce40423ac6b22021-12-02T11:53:00ZMonocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation10.1038/s41598-017-06202-22045-2322https://doaj.org/article/c8ed2a39083f4ac783ecce40423ac6b22017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06202-2https://doaj.org/toc/2045-2322Abstract 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.Bamaprasad DuttaJung Eun ParkSubodh KumarPiliang HaoXavier Gallart-PalauAida SerraYan RenVitaly SorokinChuen Neng LeeHee Hwa HoDominique de KleijnSiu Kwan SzeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bamaprasad Dutta Jung Eun Park Subodh Kumar Piliang Hao Xavier Gallart-Palau Aida Serra Yan Ren Vitaly Sorokin Chuen Neng Lee Hee Hwa Ho Dominique de Kleijn Siu Kwan Sze Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation
description	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.
format	article
author	Bamaprasad Dutta Jung Eun Park Subodh Kumar Piliang Hao Xavier Gallart-Palau Aida Serra Yan Ren Vitaly Sorokin Chuen Neng Lee Hee Hwa Ho Dominique de Kleijn Siu Kwan Sze
author_facet	Bamaprasad Dutta Jung Eun Park Subodh Kumar Piliang Hao Xavier Gallart-Palau Aida Serra Yan Ren Vitaly Sorokin Chuen Neng Lee Hee Hwa Ho Dominique de Kleijn Siu Kwan Sze
author_sort	Bamaprasad Dutta
title	Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation
title_short	Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation
title_full	Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation
title_fullStr	Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation
title_full_unstemmed	Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation
title_sort	monocyte adhesion to atherosclerotic matrix proteins is enhanced by asn-gly-arg deamidation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c8ed2a39083f4ac783ecce40423ac6b2
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Monocyte adhesion to atherosclerotic matrix proteins is enhanced by Asn-Gly-Arg deamidation

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