SARS-CoV-2 infection downregulates myocardial ACE2 and potentiates cardiac inflammation in humans and hamsters.
Anissa ViveirosRyan S NoyceMahmoud GheblawiDaniele ColomboLeanne M BilawchukXavier Clemente-CasaresDavid J MarchantZamaneh KassiriFranca Del NonnoDavid H EvansGavin Y OuditPublished in: American journal of physiology. Heart and circulatory physiology (2022)
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.
Keyphrases
- sars cov
- angiotensin converting enzyme
- left ventricular
- respiratory syndrome coronavirus
- angiotensin ii
- oxidative stress
- endothelial cells
- cell proliferation
- single cell
- heart failure
- signaling pathway
- coronavirus disease
- induced apoptosis
- poor prognosis
- risk factors
- endoplasmic reticulum stress
- mesenchymal stem cells
- dendritic cells
- acute myeloid leukemia
- pulmonary hypertension