The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein

Abstract Atherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and interna...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bushra Yusuf, Ilya Mukovozov, Sajedabanu Patel, Yi-Wei Huang, Guang Ying Liu, Emily C. Reddy, Marko Skrtic, Michael Glogauer, Lisa A. Robinson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/692c0813c2d5464cb7a9503427c02397
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:692c0813c2d5464cb7a9503427c02397
record_format	dspace
spelling	oai:doaj.org-article:692c0813c2d5464cb7a9503427c023972021-12-02T14:26:47ZThe neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein10.1038/s41598-021-83046-x2045-2322https://doaj.org/article/692c0813c2d5464cb7a9503427c023972021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83046-xhttps://doaj.org/toc/2045-2322Abstract Atherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.Bushra YusufIlya MukovozovSajedabanu PatelYi-Wei HuangGuang Ying LiuEmily C. ReddyMarko SkrticMichael GlogauerLisa A. RobinsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bushra Yusuf Ilya Mukovozov Sajedabanu Patel Yi-Wei Huang Guang Ying Liu Emily C. Reddy Marko Skrtic Michael Glogauer Lisa A. Robinson The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein
description	Abstract Atherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.
format	article
author	Bushra Yusuf Ilya Mukovozov Sajedabanu Patel Yi-Wei Huang Guang Ying Liu Emily C. Reddy Marko Skrtic Michael Glogauer Lisa A. Robinson
author_facet	Bushra Yusuf Ilya Mukovozov Sajedabanu Patel Yi-Wei Huang Guang Ying Liu Emily C. Reddy Marko Skrtic Michael Glogauer Lisa A. Robinson
author_sort	Bushra Yusuf
title	The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein
title_short	The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein
title_full	The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein
title_fullStr	The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein
title_full_unstemmed	The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein
title_sort	neurorepellent, slit2, prevents macrophage lipid loading by inhibiting cd36-dependent binding and internalization of oxidized low-density lipoprotein
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/692c0813c2d5464cb7a9503427c02397
work_keys_str_mv	AT bushrayusuf theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT ilyamukovozov theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT sajedabanupatel theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT yiweihuang theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT guangyingliu theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT emilycreddy theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT markoskrtic theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT michaelglogauer theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT lisaarobinson theneurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT bushrayusuf neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT ilyamukovozov neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT sajedabanupatel neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT yiweihuang neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT guangyingliu neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT emilycreddy neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT markoskrtic neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT michaelglogauer neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein AT lisaarobinson neurorepellentslit2preventsmacrophagelipidloadingbyinhibitingcd36dependentbindingandinternalizationofoxidizedlowdensitylipoprotein
_version_	1718391314428461056

The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein

Ejemplares similares