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Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits

Accumulated evidence shows that elevated urotensin II (UII) levels are associated with cardiovascular diseases. However, the role of UII in the initiation, progression, and regression of atherosclerosis remains to be verified. Different stages of atherosclerosis were induced in rabbits by a 0.3% hig...

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Autores principales: Yu, Qingqing, Wei, Panpan, Xu, Liran, Xia, Congcong, Li, Yafeng, Liu, Haole, Song, Xiaojie, Tian, Kangli, Fu, Weilai, Wang, Rong, Wang, Weirong, Bai, Liang, Fan, Jianglin, Liu, Enqi, Zhao, Sihai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963243/
https://www.ncbi.nlm.nih.gov/pubmed/36835230
http://dx.doi.org/10.3390/ijms24043819
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author Yu, Qingqing
Wei, Panpan
Xu, Liran
Xia, Congcong
Li, Yafeng
Liu, Haole
Song, Xiaojie
Tian, Kangli
Fu, Weilai
Wang, Rong
Wang, Weirong
Bai, Liang
Fan, Jianglin
Liu, Enqi
Zhao, Sihai
author_facet Yu, Qingqing
Wei, Panpan
Xu, Liran
Xia, Congcong
Li, Yafeng
Liu, Haole
Song, Xiaojie
Tian, Kangli
Fu, Weilai
Wang, Rong
Wang, Weirong
Bai, Liang
Fan, Jianglin
Liu, Enqi
Zhao, Sihai
author_sort Yu, Qingqing
collection PubMed
description Accumulated evidence shows that elevated urotensin II (UII) levels are associated with cardiovascular diseases. However, the role of UII in the initiation, progression, and regression of atherosclerosis remains to be verified. Different stages of atherosclerosis were induced in rabbits by a 0.3% high cholesterol diet (HCD) feeding, and either UII (5.4 μg/kg/h) or saline was chronically infused via osmotic mini-pumps. UII promoted atherosclerotic fatty streak formation in ovariectomized female rabbits (34% increase in gross lesion and 93% increase in microscopic lesion), and in male rabbits (39% increase in gross lesion). UII infusion significantly increased the plaque size of the carotid and subclavian arteries (69% increase over the control). In addition, UII infusion significantly enhanced the development of coronary lesions by increasing plaque size and lumen stenosis. Histopathological analysis revealed that aortic lesions in the UII group were characterized by increasing lesional macrophages, lipid deposition, and intra-plaque neovessel formation. UII infusion also significantly delayed the regression of atherosclerosis in rabbits by increasing the intra-plaque macrophage ratio. Furthermore, UII treatment led to a significant increase in NOX2 and HIF-1α/VEGF-A expression accompanied by increased reactive oxygen species levels in cultured macrophages. Tubule formation assays showed that UII exerted a pro-angiogenic effect in cultured endothelial cell lines and this effect was partly inhibited by urantide, a UII receptor antagonist. These findings suggest that UII can accelerate aortic and coronary plaque formation and enhance aortic plaque vulnerability, but delay the regression of atherosclerosis. The role of UII on angiogenesis in the lesion may be involved in complex plaque development.
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spelling pubmed-99632432023-02-26 Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits Yu, Qingqing Wei, Panpan Xu, Liran Xia, Congcong Li, Yafeng Liu, Haole Song, Xiaojie Tian, Kangli Fu, Weilai Wang, Rong Wang, Weirong Bai, Liang Fan, Jianglin Liu, Enqi Zhao, Sihai Int J Mol Sci Article Accumulated evidence shows that elevated urotensin II (UII) levels are associated with cardiovascular diseases. However, the role of UII in the initiation, progression, and regression of atherosclerosis remains to be verified. Different stages of atherosclerosis were induced in rabbits by a 0.3% high cholesterol diet (HCD) feeding, and either UII (5.4 μg/kg/h) or saline was chronically infused via osmotic mini-pumps. UII promoted atherosclerotic fatty streak formation in ovariectomized female rabbits (34% increase in gross lesion and 93% increase in microscopic lesion), and in male rabbits (39% increase in gross lesion). UII infusion significantly increased the plaque size of the carotid and subclavian arteries (69% increase over the control). In addition, UII infusion significantly enhanced the development of coronary lesions by increasing plaque size and lumen stenosis. Histopathological analysis revealed that aortic lesions in the UII group were characterized by increasing lesional macrophages, lipid deposition, and intra-plaque neovessel formation. UII infusion also significantly delayed the regression of atherosclerosis in rabbits by increasing the intra-plaque macrophage ratio. Furthermore, UII treatment led to a significant increase in NOX2 and HIF-1α/VEGF-A expression accompanied by increased reactive oxygen species levels in cultured macrophages. Tubule formation assays showed that UII exerted a pro-angiogenic effect in cultured endothelial cell lines and this effect was partly inhibited by urantide, a UII receptor antagonist. These findings suggest that UII can accelerate aortic and coronary plaque formation and enhance aortic plaque vulnerability, but delay the regression of atherosclerosis. The role of UII on angiogenesis in the lesion may be involved in complex plaque development. MDPI 2023-02-14 /pmc/articles/PMC9963243/ /pubmed/36835230 http://dx.doi.org/10.3390/ijms24043819 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
Yu, Qingqing
Wei, Panpan
Xu, Liran
Xia, Congcong
Li, Yafeng
Liu, Haole
Song, Xiaojie
Tian, Kangli
Fu, Weilai
Wang, Rong
Wang, Weirong
Bai, Liang
Fan, Jianglin
Liu, Enqi
Zhao, Sihai
Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits
title Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits
title_full Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits
title_fullStr Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits
title_full_unstemmed Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits
title_short Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits
title_sort urotensin ii enhances advanced aortic atherosclerosis formation and delays plaque regression in hyperlipidemic rabbits
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963243/
https://www.ncbi.nlm.nih.gov/pubmed/36835230
http://dx.doi.org/10.3390/ijms24043819
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