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Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2

Objective: AIP1 expression is downregulated in human atherosclerotic plaques and global deletion of AIP1 in mice exacerbates atherosclerosis in ApoE-KO mouse models. However, the direct role of AIP1 in endothelium, vascular remodeling and associated vascular diseases has not been determined. Approac...

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Autores principales: Zhang, Jiqin, Chen, Chaofei, Li, Li, Zhou, Huanjiao J., Li, Fenghe, Zhang, Haifeng, Yu, Luyang, Chen, Yuxin, Min, Wang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921534/
https://www.ncbi.nlm.nih.gov/pubmed/29731721
http://dx.doi.org/10.3389/fphys.2018.00396
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author Zhang, Jiqin
Chen, Chaofei
Li, Li
Zhou, Huanjiao J.
Li, Fenghe
Zhang, Haifeng
Yu, Luyang
Chen, Yuxin
Min, Wang
author_facet Zhang, Jiqin
Chen, Chaofei
Li, Li
Zhou, Huanjiao J.
Li, Fenghe
Zhang, Haifeng
Yu, Luyang
Chen, Yuxin
Min, Wang
author_sort Zhang, Jiqin
collection PubMed
description Objective: AIP1 expression is downregulated in human atherosclerotic plaques and global deletion of AIP1 in mice exacerbates atherosclerosis in ApoE-KO mouse models. However, the direct role of AIP1 in endothelium, vascular remodeling and associated vascular diseases has not been determined. Approach and Results: We used endothelial cell (EC)-specific AIP1-deficient (AIP1-ECKO) mice to define the role of AIP1 in vascular remodeling and intima-media thickening in a mouse carotid artery ligation model characterized by both neointimal hyperplasia and inward vessel remodeling. Compared to WT littermates, AIP1-ECKO mice had 2.2-fold larger intima area and 4.4-fold thicker intima as measured by intima/media ratio in arteries with more proliferating vascular smooth muscle cells (VSMCs) at week 2–4 post-injury. Increased reactive oxygen species (ROS) in endothelium at early time points induced inflammation and vessel dysfunction in AIP1-ECKO prior to VSMC accumulations. Moreover, knockdown of AIP1 in human EC enhanced ROS generation which was attenuated by co-silencing of NOX2. Mechanistically, AIP1 via its proline-rich region binds to the SH3 domain of cytosolic subunit p47phox to disrupt formation of an active NOX2 complex, attenuating ROS production. Conclusion: Our study supports that AIP1 regulates vascular remodeling with intima-media thickening by suppressing endothelial NOX2-dependent oxidative stress. Highlights: • In a carotid ligation model, endothelial cell (EC)-specific AIP1-deficient (AIP1-ECKO) mice had much larger media area, thicker vessel wall and augmented neointima formation. • Increased production of reactive oxygen species in vascular EC at early time points concomitant with vessel dysfunction in AIP1-ECKO. • AIP1 via its proline-rich region binds to the SH3 domain of cytosolic subunit p47phox to disrupt formation of an active NOX2 complex, attenuating ROS production.
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spelling pubmed-59215342018-05-04 Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2 Zhang, Jiqin Chen, Chaofei Li, Li Zhou, Huanjiao J. Li, Fenghe Zhang, Haifeng Yu, Luyang Chen, Yuxin Min, Wang Front Physiol Physiology Objective: AIP1 expression is downregulated in human atherosclerotic plaques and global deletion of AIP1 in mice exacerbates atherosclerosis in ApoE-KO mouse models. However, the direct role of AIP1 in endothelium, vascular remodeling and associated vascular diseases has not been determined. Approach and Results: We used endothelial cell (EC)-specific AIP1-deficient (AIP1-ECKO) mice to define the role of AIP1 in vascular remodeling and intima-media thickening in a mouse carotid artery ligation model characterized by both neointimal hyperplasia and inward vessel remodeling. Compared to WT littermates, AIP1-ECKO mice had 2.2-fold larger intima area and 4.4-fold thicker intima as measured by intima/media ratio in arteries with more proliferating vascular smooth muscle cells (VSMCs) at week 2–4 post-injury. Increased reactive oxygen species (ROS) in endothelium at early time points induced inflammation and vessel dysfunction in AIP1-ECKO prior to VSMC accumulations. Moreover, knockdown of AIP1 in human EC enhanced ROS generation which was attenuated by co-silencing of NOX2. Mechanistically, AIP1 via its proline-rich region binds to the SH3 domain of cytosolic subunit p47phox to disrupt formation of an active NOX2 complex, attenuating ROS production. Conclusion: Our study supports that AIP1 regulates vascular remodeling with intima-media thickening by suppressing endothelial NOX2-dependent oxidative stress. Highlights: • In a carotid ligation model, endothelial cell (EC)-specific AIP1-deficient (AIP1-ECKO) mice had much larger media area, thicker vessel wall and augmented neointima formation. • Increased production of reactive oxygen species in vascular EC at early time points concomitant with vessel dysfunction in AIP1-ECKO. • AIP1 via its proline-rich region binds to the SH3 domain of cytosolic subunit p47phox to disrupt formation of an active NOX2 complex, attenuating ROS production. Frontiers Media S.A. 2018-04-20 /pmc/articles/PMC5921534/ /pubmed/29731721 http://dx.doi.org/10.3389/fphys.2018.00396 Text en Copyright © 2018 Zhang, Chen, Li, Zhou, Li, Zhang, Yu, Chen and Min. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Zhang, Jiqin
Chen, Chaofei
Li, Li
Zhou, Huanjiao J.
Li, Fenghe
Zhang, Haifeng
Yu, Luyang
Chen, Yuxin
Min, Wang
Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2
title Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2
title_full Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2
title_fullStr Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2
title_full_unstemmed Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2
title_short Endothelial AIP1 Regulates Vascular Remodeling by Suppressing NADPH Oxidase-2
title_sort endothelial aip1 regulates vascular remodeling by suppressing nadph oxidase-2
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921534/
https://www.ncbi.nlm.nih.gov/pubmed/29731721
http://dx.doi.org/10.3389/fphys.2018.00396
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