Frontiers in Medicine (Mar 2023)
Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis
- Camilla Margaroli,
- Camilla Margaroli,
- Paul Benson,
- Maria G. Gastanadui,
- Maria G. Gastanadui,
- Chunyan Song,
- Chunyan Song,
- Chunyan Song,
- Liliana Viera,
- Liliana Viera,
- Liliana Viera,
- Dongqi Xing,
- Dongqi Xing,
- Dongqi Xing,
- Dongqi Xing,
- Dongqi Xing,
- J. Michael Wells,
- J. Michael Wells,
- J. Michael Wells,
- J. Michael Wells,
- J. Michael Wells,
- J. Michael Wells,
- Rakesh Patel,
- Rakesh Patel,
- Rakesh Patel,
- Amit Gaggar,
- Amit Gaggar,
- Amit Gaggar,
- Amit Gaggar,
- Amit Gaggar,
- Amit Gaggar,
- Amit Gaggar,
- Gregory A. Payne,
- Gregory A. Payne,
- Gregory A. Payne,
- Gregory A. Payne,
- Gregory A. Payne,
- Gregory A. Payne
Affiliations
- Camilla Margaroli
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Camilla Margaroli
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Paul Benson
- Department of Pathology, Division of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, AL, United States
- Maria G. Gastanadui
- Cardiopulmonary Research Program, University of Alabama at Birmingham, Birmingham, AL, United States
- Maria G. Gastanadui
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States
- Chunyan Song
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Chunyan Song
- Cardiopulmonary Research Program, University of Alabama at Birmingham, Birmingham, AL, United States
- Chunyan Song
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States
- Liliana Viera
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Liliana Viera
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Liliana Viera
- Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, United States
- Dongqi Xing
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Dongqi Xing
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Dongqi Xing
- Cardiopulmonary Research Program, University of Alabama at Birmingham, Birmingham, AL, United States
- Dongqi Xing
- Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, United States
- Dongqi Xing
- Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, United States
- J. Michael Wells
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- J. Michael Wells
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- J. Michael Wells
- Cardiopulmonary Research Program, University of Alabama at Birmingham, Birmingham, AL, United States
- J. Michael Wells
- Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, United States
- J. Michael Wells
- Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, United States
- J. Michael Wells
- Medical Service at Birmingham VA Medical Center, Birmingham, AL, United States
- Rakesh Patel
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Rakesh Patel
- Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL, United States
- Rakesh Patel
- 0Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Amit Gaggar
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
- Amit Gaggar
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Amit Gaggar
- Cardiopulmonary Research Program, University of Alabama at Birmingham, Birmingham, AL, United States
- Amit Gaggar
- Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, United States
- Amit Gaggar
- Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, United States
- Amit Gaggar
- Medical Service at Birmingham VA Medical Center, Birmingham, AL, United States
- Amit Gaggar
- 1Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Gregory A. Payne
- Program in Protease/Matrix Biology, University of Alabama at Birmingham, Birmingham, AL, United States
- Gregory A. Payne
- Cardiopulmonary Research Program, University of Alabama at Birmingham, Birmingham, AL, United States
- Gregory A. Payne
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, United States
- Gregory A. Payne
- Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, United States
- Gregory A. Payne
- Medical Service at Birmingham VA Medical Center, Birmingham, AL, United States
- Gregory A. Payne
- 2Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL, United States
- DOI
- https://doi.org/10.3389/fmed.2023.1118024
- Journal volume & issue
-
Vol. 10
Abstract
ObjectivesOur objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics.BackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear.MethodsAutopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue.ResultsWe observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels.ConclusionOur results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis, and endothelial activation as key drivers of cardiovascular events during COVID-19.
Keywords
- spatial transcriptomic
- severe acute respiratory syndrome coronavirus-2
- myocarditis
- endothelium
- cell programming
