A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke
Abstract 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...
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| Format: | Article |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17546-9 |
| _version_ | 1811315294286643200 |
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| author | Hernan A. Bazan Ashton J. Brooks Kenny Vongbunyong Christin Tee Hunter F. Douglas Natasha C. Klingenberg T. Cooper Woods |
| author_facet | Hernan A. Bazan Ashton J. Brooks Kenny Vongbunyong Christin Tee Hunter F. Douglas Natasha C. Klingenberg T. Cooper Woods |
| author_sort | Hernan A. Bazan |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T11:27:42Z |
| format | Article |
| id | doaj.art-9a12952fdb3e4c2098a91a2edb791018 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T11:27:42Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9a12952fdb3e4c2098a91a2edb7910182022-12-22T02:48:39ZengNature PortfolioScientific Reports2045-23222022-08-011211810.1038/s41598-022-17546-9A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to strokeHernan A. Bazan0Ashton J. Brooks1Kenny Vongbunyong2Christin Tee3Hunter F. Douglas4Natasha C. Klingenberg5T. Cooper Woods6Section of Vascular/Endovascular Surgery, Department of Surgery, Ochsner Clinic FoundationSection of Vascular/Endovascular Surgery, Department of Surgery, Ochsner Clinic FoundationDepartments of Physiology and Medicine, Tulane University School of MedicineDepartments of Physiology and Medicine, Tulane University School of MedicineDepartments of Physiology and Medicine, Tulane University School of MedicineDepartments of Physiology and Medicine, Tulane University School of MedicineDepartments of Physiology and Medicine, Tulane University School of MedicineAbstract 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.https://doi.org/10.1038/s41598-022-17546-9 |
| spellingShingle | Hernan A. Bazan Ashton J. Brooks Kenny Vongbunyong Christin Tee Hunter F. Douglas Natasha C. Klingenberg T. Cooper Woods A pro-inflammatory and fibrous cap thinning transcriptome profile accompanies carotid plaque rupture leading to stroke Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-17546-9 |
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