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| Status |
Public on Jul 16, 2021 |
| Title |
RNA Sequencing of Blood in Coronary Artery Disease; Involvement of Regulatory T Cell Imbalance [Validation Cohort] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Background: Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography. Surprisingly, despite well-established clinical indications, up to 40% of the one million invasive cardiac catheterizations return a result of ‘no blockage’. The present studies employed RNA sequencing of whole blood to identify an RNA signature in patients presenting with a clinical suspicion of CAD.
Methods: Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by single-molecule sequencing of RNA (RNAseq) to identify transcripts associated with CAD (TRACs) in a discovery group of 96 patients presenting for elective coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs). Results: Surprisingly, 98% of DEGs/TRACs were down-regulated ~1.7-fold in patients with mild to severe CAD (>20% stenosis). The TRACs were independent of comorbid risk factors for CAD, such as gender, hypertension, and smoking. Bioinformatic analysis identified an enrichment in transcripts such as FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A that are likely markers of regulatory T cells (Treg), consistent with known reductions in Tregs in CAD. A validation cohort of 80 patients confirmed the overall pattern (92% down-regulation) and supported many of the Treg-related changes. TRACs were enriched for transcripts associated with stress granules, which sequester RNAs, and ciliary and synaptic transcripts, possibly consistent with changes in the immune synapse of developing T cells.
Conclusions: These studies identify a novel mRNA signature of a Treg-like defect in CAD patients and provides a blueprint for a diagnostic test for CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.
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| Overall design |
Observational study; no intervention; CAD defined by Invasive Coronary Angiography; CAD defined as >20% stenosis
*** Raw data not submitted due to patient privacy concerns. Sequence files will be provided separately to users that can provide IRB and HIPPAA assurances. ***
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| |
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| Contributor(s) |
McCaffrey TA |
| Citation(s) |
34479557, 37303712 |
| Submission date |
Jul 14, 2021 |
| Last update date |
Sep 07, 2023 |
| Contact name |
Timothy McCaffrey |
| E-mail(s) |
mcc@gwu.edu
|
| Phone |
202-994-8919
|
| Organization name |
The George Washington University
|
| Department |
Department of Biochemisty & Molecular Biology
|
| Street address |
2300 I Street NW
|
| City |
Washington |
| State/province |
DC |
| ZIP/Postal code |
20037 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL14761 |
Helicos HeliScope (Homo sapiens) |
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| Samples (80)
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| This SubSeries is part of SuperSeries: |
| GSE180083 |
RNA Sequencing of Blood in Coronary Artery Disease; Involvement of Regulatory T Cell Imbalance |
|
| Relations |
| BioProject |
PRJNA746486 |
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