SARS-CoV-2 infection downregulates myocardial ACE2 and potentiates cardiac inflammation in humans and hamsters.
Am J Physiol Heart Circ Physiol
; 323(6): H1262-H1269, 2022 Dec 01.
Article
in English
| MEDLINE | ID: covidwho-2117986
ABSTRACT
Myocardial pathologies resulting from SARS-CoV-2 infections are consistently rising with mounting case rates and reinfections; however, the precise global burden is largely unknown and will have an unprecedented impact. Understanding the mechanisms of COVID-19-mediated cardiac injury is essential toward the development of cardioprotective agents that are urgently needed. Assessing novel therapeutic strategies to tackle COVID-19 necessitates an animal model that recapitulates human disease. Here, we sought to compare SARS-CoV-2-infected animals with patients with COVID-19 to identify common mechanisms of cardiac injury. Two-month-old hamsters were infected with either the ancestral (D614) or Delta variant (B.1.617.2) of SARS-CoV-2 for 2 days, 7 days, and/or 14 days. We measured viral RNA and cytokine expression at the earlier time points to capture the initial stages of infection in the lung and heart. We assessed myocardial angiotensin-converting enzyme 2 (ACE2), the entry receptor for the SARS-CoV-2 virus, and cardioprotective enzyme, as well as markers for inflammatory cell infiltration in the hamster hearts at days 7 and 14. In parallel, human hearts were stained for ACE2, viral nucleocapsid, and inflammatory cells. Indeed, we identify myocardial ACE2 downregulation and myeloid cell burden as common events in both hamsters and humans infected with SARS-CoV-2, and we propose targeting downstream ACE2 downregulation as a therapeutic avenue that warrants clinical investigation.NEW & NOTEWORTHY Cardiac manifestations of COVID-19 in humans are mirrored in the SARS-CoV-2 hamster model, recapitulating myocardial damage, ACE2 downregulation, and a consistent pattern of immune cell infiltration independent of viral dose and variant. Therefore, the hamster model is a valid approach to study therapeutic strategies for COVID-19-related heart disease.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Angiotensin-Converting Enzyme 2
/
COVID-19
Type of study:
Prognostic study
Topics:
Variants
Limits:
Animals
/
Humans
/
Infant
Language:
English
Journal:
Am J Physiol Heart Circ Physiol
Journal subject:
Cardiology
/
Physiology
Year:
2022
Document Type:
Article
Affiliation country:
Ajpheart.00578.2022
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