SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels
- Description
This study combined multiple techniques (e.g., RNAscope in-situ hybridization, immunohistochemistry, immunofluorescence, single-cell RNA sequencing, bulk RNA sequencing, and functional assays) to investigate the inflammatory response associated with SARS-CoV-2 infection in human vascular tissues. Single cell RNA-sequencing data obtained from samples collected for this study is available via the Gene Expression Omnibus (GEO).
27 coronary autopsy specimens were collected from 8 patients (mean age of 69.6 years) with a RT-PCR-confirmed diagnosis of COVID-19 between May 2020 and May 2021. All patients had coronary artery disease and three or more cardiovascular disease risk factors (e.g., hypertension). Fresh carotid plaque specimens were obtained from 10 patients undergoing carotid endarterectomy enrolled in a separate study (Athero-IN). These plaques were classified by a clinical cardiovascular pathologist (fibrocalcific, fibroatheroma, or unclassifiable) and processed for single cell RNA sequencing. To produce macrophages, human primary monocytes were exposed to human macrophage-colony stimulating factor in culture media; the macrophages and foam cells extracted from human aortic smooth muscle were then infected in-vitro with SARS-CoV-2 virus to examine differential interferon response and virus clearance dynamics as well as quantify the secretion of cytokines and chemokines. Ex-vivo SARS-CoV-2 infection of human vascular explants was performed for bulk RNA sequencing and NRP-1 blocking experiments. Specimen collection, processing, and analysis are detailed further in the associated publication.
- Timeframe
- 2020 - 2021
- Geographic Coverage
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New York (State) - New York City
Access
- Restrictions
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Free to All
- Instructions
- Sequencing data and code is available through the Gene Expression Omnibus (GEO) and GitHub repositories, respectively. Other data utilized in analyses that were reported in the associated publication can be accessed through the links under Other Resources.
- Grant Support
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NFL-2020-218415/Chan Zuckerberg Initiative20SFRN35210252/American Heart AssociationAHA 965509/American Heart AssociationPostdoctoral Fellowship 19-A0-00-1003686/American Heart Association
- Other Resources
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Common Fund (CF) Genotype-Tissue Expression Project (GTEx)
dbGap data release
Single cell RNA sequencing of vascular smooth muscle cells from atherosclerotic lesions of ApoE ko miceMurine scRNA-seq data
The Human Genome Project at Genome Reference ConsortiumGenome assembly GRCh38
GenBankSARS-CoV-2 genome