Cargando…

Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization

The RhoA-specific guanine nucleotide exchange factor p190RhoGEF has been implicated in the control of cell morphology, focal adhesion formation, and cell motility. Previously, we reported that p190RhoGEF is also active in various immune cells. In this study, we examined whether over-expression of p1...

Descripción completa

Detalles Bibliográficos
Autores principales: Choi, So-Yeon, Lee, Eun-Bi, Kim, Jee-Hae, Lee, Jong Ran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454661/
https://www.ncbi.nlm.nih.gov/pubmed/37628966
http://dx.doi.org/10.3390/ijms241612785
_version_ 1785096249407438848
author Choi, So-Yeon
Lee, Eun-Bi
Kim, Jee-Hae
Lee, Jong Ran
author_facet Choi, So-Yeon
Lee, Eun-Bi
Kim, Jee-Hae
Lee, Jong Ran
author_sort Choi, So-Yeon
collection PubMed
description The RhoA-specific guanine nucleotide exchange factor p190RhoGEF has been implicated in the control of cell morphology, focal adhesion formation, and cell motility. Previously, we reported that p190RhoGEF is also active in various immune cells. In this study, we examined whether over-expression of p190RhoGEF could affect atherosclerotic plaque formation in mouse aortae. For that purpose, transgenic (TG) mice over-expressing p190RhoGEF were cross-bred with atherosclerosis-prone apolipoprotein E (ApoE)(−/−) mice to obtain p190RhoGEF-TG mice with ApoE(−/−) backgrounds (TG/ApoE(−/−)). Aortic plaque formation was significantly increased in TG/ApoE mice(−/−) at 30 to 40 weeks of age compared to that in ApoE(−/−) mice. Serum concentrations of inflammatory cytokines (IL-6 and TNF-α) were greater in TG/ApoE(−/−) mice than in ApoE(−/−) mice at ~40 weeks of age. Furthermore, TG/ApoE(−/−) mice had a greater proportion of peritoneal macrophages within the M1 subset at 30 to 40 weeks of age, together with higher production of inflammatory cytokines and stronger responses to bacterial lipopolysaccharide than ApoE(−/−) mice. Collectively, these results highlight a crucial role of enhanced p190RhoGEF expression in atherosclerosis progression, including the activation of pro-inflammatory M1 macrophages.
format Online
Article
Text
id pubmed-10454661
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-104546612023-08-26 Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization Choi, So-Yeon Lee, Eun-Bi Kim, Jee-Hae Lee, Jong Ran Int J Mol Sci Article The RhoA-specific guanine nucleotide exchange factor p190RhoGEF has been implicated in the control of cell morphology, focal adhesion formation, and cell motility. Previously, we reported that p190RhoGEF is also active in various immune cells. In this study, we examined whether over-expression of p190RhoGEF could affect atherosclerotic plaque formation in mouse aortae. For that purpose, transgenic (TG) mice over-expressing p190RhoGEF were cross-bred with atherosclerosis-prone apolipoprotein E (ApoE)(−/−) mice to obtain p190RhoGEF-TG mice with ApoE(−/−) backgrounds (TG/ApoE(−/−)). Aortic plaque formation was significantly increased in TG/ApoE mice(−/−) at 30 to 40 weeks of age compared to that in ApoE(−/−) mice. Serum concentrations of inflammatory cytokines (IL-6 and TNF-α) were greater in TG/ApoE(−/−) mice than in ApoE(−/−) mice at ~40 weeks of age. Furthermore, TG/ApoE(−/−) mice had a greater proportion of peritoneal macrophages within the M1 subset at 30 to 40 weeks of age, together with higher production of inflammatory cytokines and stronger responses to bacterial lipopolysaccharide than ApoE(−/−) mice. Collectively, these results highlight a crucial role of enhanced p190RhoGEF expression in atherosclerosis progression, including the activation of pro-inflammatory M1 macrophages. MDPI 2023-08-14 /pmc/articles/PMC10454661/ /pubmed/37628966 http://dx.doi.org/10.3390/ijms241612785 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, So-Yeon
Lee, Eun-Bi
Kim, Jee-Hae
Lee, Jong Ran
Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization
title Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization
title_full Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization
title_fullStr Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization
title_full_unstemmed Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization
title_short Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE(−/−) Mice via Macrophage Polarization
title_sort over-expression of p190rhogef regulates the formation of atherosclerotic plaques in the aorta of apoe(−/−) mice via macrophage polarization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454661/
https://www.ncbi.nlm.nih.gov/pubmed/37628966
http://dx.doi.org/10.3390/ijms241612785
work_keys_str_mv AT choisoyeon overexpressionofp190rhogefregulatestheformationofatheroscleroticplaquesintheaortaofapoemiceviamacrophagepolarization
AT leeeunbi overexpressionofp190rhogefregulatestheformationofatheroscleroticplaquesintheaortaofapoemiceviamacrophagepolarization
AT kimjeehae overexpressionofp190rhogefregulatestheformationofatheroscleroticplaquesintheaortaofapoemiceviamacrophagepolarization
AT leejongran overexpressionofp190rhogefregulatestheformationofatheroscleroticplaquesintheaortaofapoemiceviamacrophagepolarization