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Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice

A better understanding of endothelial dysfunction holds promise for more effective interventions for atherosclerosis prevention and treatment. Endothelial signaling by the non-catalytic region of the tyrosine kinase (NCK) family of adaptors, consisting of NCK1 and NCK2, has been implicated in cardio...

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Autores principales: Bywaters, Briana C., Pedraza, Gladys, Trache, Andreea, Rivera, Gonzalo M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413153/
https://www.ncbi.nlm.nih.gov/pubmed/36035930
http://dx.doi.org/10.3389/fcvm.2022.955027
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author Bywaters, Briana C.
Pedraza, Gladys
Trache, Andreea
Rivera, Gonzalo M.
author_facet Bywaters, Briana C.
Pedraza, Gladys
Trache, Andreea
Rivera, Gonzalo M.
author_sort Bywaters, Briana C.
collection PubMed
description A better understanding of endothelial dysfunction holds promise for more effective interventions for atherosclerosis prevention and treatment. Endothelial signaling by the non-catalytic region of the tyrosine kinase (NCK) family of adaptors, consisting of NCK1 and NCK2, has been implicated in cardiovascular development and postnatal angiogenesis but its role in vascular disease remains incompletely understood. Here, we report stage- and sex-dependent effects of endothelial NCK2 signaling on arterial wall inflammation and atherosclerosis development. Male and female Nck1-null atheroprone mice enabling inducible, endothelial-specific Nck2 inactivation were fed a high fat diet (HFD) for 8 or 16 weeks to model atherosclerosis initiation and progression, respectively. Analysis of aorta preparations en face during disease progression, but not initiation, showed a significant reduction in plaque burden in males, but not females, lacking endothelial NCK2 relative to controls. Markers of vascular inflammation were reduced by endothelial NCK2 deficiency in both males and females during atherosclerosis progression but not initiation. At advanced stages of disease, plaque size and severity of atherosclerotic lesions were reduced by abrogation of endothelial NCK2 signaling only in males. Collectively, our results demonstrate stage- and sex-dependent modulation of atherosclerosis development by endothelial NCK2 signaling.
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spelling pubmed-94131532022-08-27 Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice Bywaters, Briana C. Pedraza, Gladys Trache, Andreea Rivera, Gonzalo M. Front Cardiovasc Med Cardiovascular Medicine A better understanding of endothelial dysfunction holds promise for more effective interventions for atherosclerosis prevention and treatment. Endothelial signaling by the non-catalytic region of the tyrosine kinase (NCK) family of adaptors, consisting of NCK1 and NCK2, has been implicated in cardiovascular development and postnatal angiogenesis but its role in vascular disease remains incompletely understood. Here, we report stage- and sex-dependent effects of endothelial NCK2 signaling on arterial wall inflammation and atherosclerosis development. Male and female Nck1-null atheroprone mice enabling inducible, endothelial-specific Nck2 inactivation were fed a high fat diet (HFD) for 8 or 16 weeks to model atherosclerosis initiation and progression, respectively. Analysis of aorta preparations en face during disease progression, but not initiation, showed a significant reduction in plaque burden in males, but not females, lacking endothelial NCK2 relative to controls. Markers of vascular inflammation were reduced by endothelial NCK2 deficiency in both males and females during atherosclerosis progression but not initiation. At advanced stages of disease, plaque size and severity of atherosclerotic lesions were reduced by abrogation of endothelial NCK2 signaling only in males. Collectively, our results demonstrate stage- and sex-dependent modulation of atherosclerosis development by endothelial NCK2 signaling. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9413153/ /pubmed/36035930 http://dx.doi.org/10.3389/fcvm.2022.955027 Text en Copyright © 2022 Bywaters, Pedraza, Trache and Rivera. https://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(s) 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 Cardiovascular Medicine
Bywaters, Briana C.
Pedraza, Gladys
Trache, Andreea
Rivera, Gonzalo M.
Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice
title Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice
title_full Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice
title_fullStr Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice
title_full_unstemmed Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice
title_short Endothelial NCK2 promotes atherosclerosis progression in male but not female Nck1-null atheroprone mice
title_sort endothelial nck2 promotes atherosclerosis progression in male but not female nck1-null atheroprone mice
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413153/
https://www.ncbi.nlm.nih.gov/pubmed/36035930
http://dx.doi.org/10.3389/fcvm.2022.955027
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