Imperial College London
Alternate

Claire L. Shovlin PhD FRCP

Faculty of Medicine, National Heart & Lung Institute

Professor of Practice (Clinical and Molecular Medicine)
 
 
 
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Contact

 

c.shovlin Website

 
 
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Location

 

534Block L Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Shovlin:2023:qjmed/hcaa241,
author = {Shovlin, CL and Vizcaychipi, MP},
doi = {qjmed/hcaa241},
journal = {QJM: an international journal of medicine},
pages = {629--634},
title = {Vascular inflammation and endothelial injury in SARS-CoV-2 infection: the overlooked regulatory cascades implicated by the ACE2 gene cluster},
url = {http://dx.doi.org/10.1093/qjmed/hcaa241},
volume = {116},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - COVID-19 has presented physicians with an unprecedented number of challenges and mortality. The basic question is why, in contrast to other "respiratory" viruses, SARS-CoV-2 infection can result in such multi-systemic, life-threatening complications and a severe pulmonary vasculopathy. It is widely known that SARS-CoV-2 uses membrane-bound angiotensin-converting enzyme 2 (ACE2) as a receptor, resulting in internalisation of the complex by the host cell. We discuss the evidence that failure to suppress coronaviral replication within 5 days results in sustained downregulation of ACE2 protein expression, and that ACE2 is under negative-feedback regulation. We then expose openly-available experimental repository data that demonstrate the gene for ACE2 lies in a novel cluster of interegulated genes on the X chromosome including PIR encoding pirin (quercetin 2,3-dioxygenase), and VEGFD encoding the predominantly lung-expressed vascular endothelial growth factor D. The five double-elite enhancer/promoters that are known to be operational, and shared read-through lncRNA transcripts, imply that ongoing SARS-CoV-2 infection will reduce host defences to reactive oxygen species, directly generate superoxide O2 - and H2O2 (a "ROS storm"), and impair pulmonary endothelial homeostasis. Published cellular responses to oxidative stress complete the loop to pathophysiology observed in severe COVID-19. Thus for patients who fail to rapidly suppress viral replication, the newly-appreciated ACE2 co-regulated cluster predicts delayed responses that would account for catastrophic deteriorations. We conclude that ACE2 homeostatic drives provide a unified understanding which should help optimise therapeutic approaches during the wait until safe, effective vaccines and antiviral therapies for SARS-CoV-2 are delivered.
AU  - Shovlin,CL
AU  - Vizcaychipi,MP
DO  - qjmed/hcaa241
EP  - 634
PY  - 2023///
SN  - 1460-2393
SP  - 629
TI  - Vascular inflammation and endothelial injury in SARS-CoV-2 infection: the overlooked regulatory cascades implicated by the ACE2 gene cluster
T2  - QJM: an international journal of medicine
UR  - http://dx.doi.org/10.1093/qjmed/hcaa241
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32777054
UR  - https://doi.org/10.1093/qjmed/hcaa241
UR  - http://hdl.handle.net/10044/1/81984
VL  - 116
ER  -
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