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A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke

Atherosclerotic plaque rupture is the etiology of ischemic stroke and myocardial infarction. The molecular mechanisms responsible for rupture remain unclear, in part, due to the lack of data from plaques at the time of rupture. Ribosome-depleted total RNA was sequenced from carotid plaques obtained...

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Autores principales: Bazan, Hernan A., Brooks, Ashton J., Vongbunyong, Kenny, Tee, Christin, Douglas, Hunter F., Klingenberg, Natasha C., Woods, T. Cooper
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356141/
https://www.ncbi.nlm.nih.gov/pubmed/35931792
http://dx.doi.org/10.1038/s41598-022-17546-9
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author Bazan, Hernan A.
Brooks, Ashton J.
Vongbunyong, Kenny
Tee, Christin
Douglas, Hunter F.
Klingenberg, Natasha C.
Woods, T. Cooper
author_facet Bazan, Hernan A.
Brooks, Ashton J.
Vongbunyong, Kenny
Tee, Christin
Douglas, Hunter F.
Klingenberg, Natasha C.
Woods, T. Cooper
author_sort Bazan, Hernan A.
collection PubMed
description Atherosclerotic plaque rupture is the etiology of ischemic stroke and myocardial infarction. The molecular mechanisms responsible for rupture remain unclear, in part, due to the lack of data from plaques at the time of rupture. Ribosome-depleted total RNA was sequenced from carotid plaques obtained from patients undergoing carotid endarterectomy with high-grade stenosis and either (1) a carotid-related ischemic cerebrovascular event within the previous 5 days ('recently ruptured,' n = 6) or (2) an absence of a cerebrovascular event ('asymptomatic,' n = 5). Principal component analysis confirmed plaque rupture was responsible for the greatest percentage of the variability between samples (23.2%), and recently ruptured plaques were enriched for transcripts associated with inflammation and extracellular matrix degradation. Hierarchical clustering achieved differentiation of the asymptomatic from the recently ruptured plaques. This analysis also found co-expression of transcripts for immunoglobulins and B lymphocyte function, matrix metalloproteinases, and interferon response genes. Examination of the differentially expressed genes supported the importance of inflammation and inhibition of proliferation and migration coupled with an increase in apoptosis. Thus, the transcriptome of recently ruptured plaques is enriched with transcripts associated with inflammation and fibrous cap thinning and support further examination of the role of B lymphocytes and interferons in atherosclerotic plaque rupture.
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spelling pubmed-93561412022-08-07 A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke Bazan, Hernan A. Brooks, Ashton J. Vongbunyong, Kenny Tee, Christin Douglas, Hunter F. Klingenberg, Natasha C. Woods, T. Cooper Sci Rep Article Atherosclerotic plaque rupture is the etiology of ischemic stroke and myocardial infarction. The molecular mechanisms responsible for rupture remain unclear, in part, due to the lack of data from plaques at the time of rupture. Ribosome-depleted total RNA was sequenced from carotid plaques obtained from patients undergoing carotid endarterectomy with high-grade stenosis and either (1) a carotid-related ischemic cerebrovascular event within the previous 5 days ('recently ruptured,' n = 6) or (2) an absence of a cerebrovascular event ('asymptomatic,' n = 5). Principal component analysis confirmed plaque rupture was responsible for the greatest percentage of the variability between samples (23.2%), and recently ruptured plaques were enriched for transcripts associated with inflammation and extracellular matrix degradation. Hierarchical clustering achieved differentiation of the asymptomatic from the recently ruptured plaques. This analysis also found co-expression of transcripts for immunoglobulins and B lymphocyte function, matrix metalloproteinases, and interferon response genes. Examination of the differentially expressed genes supported the importance of inflammation and inhibition of proliferation and migration coupled with an increase in apoptosis. Thus, the transcriptome of recently ruptured plaques is enriched with transcripts associated with inflammation and fibrous cap thinning and support further examination of the role of B lymphocytes and interferons in atherosclerotic plaque rupture. Nature Publishing Group UK 2022-08-05 /pmc/articles/PMC9356141/ /pubmed/35931792 http://dx.doi.org/10.1038/s41598-022-17546-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bazan, Hernan A.
Brooks, Ashton J.
Vongbunyong, Kenny
Tee, Christin
Douglas, Hunter F.
Klingenberg, Natasha C.
Woods, T. Cooper
A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
title A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
title_full A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
title_fullStr A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
title_full_unstemmed A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
title_short A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
title_sort pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356141/
https://www.ncbi.nlm.nih.gov/pubmed/35931792
http://dx.doi.org/10.1038/s41598-022-17546-9
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