SARS-CoV-2 infection causes prolonged cardiomyocyte swelling and inhibition of HIF1α translocation in an animal model COVID-19
Year: 2022
Type: article
Abstract: Recovered COVID-19 patients often display cardiac dysfunction, even after a mild infection. Most current histological results come from patients that are hospitalized and therefore represent more severe outcomes than most COVID-19 patients face. To overcome this limitation, we investigated the cardiac effects of SARS-CoV-2 infection in a hamster model. SARS-CoV-2 infected hamsters developed diastolic dysfunction after recovering from COVID-19. Histologically, increased cardiomyocyte size was present at the peak of viral load and remained at all time points investigated. As this increase is too rapid for hypertrophic remodeling, we found instead that the heart was oedemic. Moreover, cardiomyocyte swelling is associated with the presence of ischemia. Fibrin-rich microthrombi and pericyte loss were observed at the peak of viral load, resulting in increased HIF1α in cardiomyocytes. Surprisingly, SARS-CoV-2 infection inhibited the translocation of HIF1α to the nucleus both in hamster hearts, in cultured cardiomyocytes, as well as in an epithelial cell line. We propose that the observed diastolic dysfunction is the consequence of cardiac oedema, downstream of microvascular cardiac ischemia. Additionally, our data suggest that inhibition of HIF1α translocation could contribute to an exaggerated response upon SARS-CoV-2 infection.
Authors: Margo Daems, Laurens Liesenborghs, Robbert Boudewijns, Steven J. Simmonds, Sirima Kraisin, Jore Van Wauwe, Ilona Cuijpers, Jana Raman, Nadèche Geuens, Tina Van Buyten, Marleen Lox, Peter Verhamme, Sophie Van Linthout, Kimberly Martinod, Stephane Heymans, Carsten Tschöpe, Johan Neyts, Elizabeth A. V. Jones
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,760
Awards: MiCrovasculaR rarefaction in vascUlar Cognitive Impairement and heArt faiLure, G2152503775, G2344375386, Cardiac microvascular regression triggers the development of Heart Failure with preserved Ejection Fraction., G2594633648, G260260998, G434337789, G4369245229, Active microvascular regression drives diastolic dysfunction leading to heart failure, G5628460097, The role of BMP signaling in early arterial differentiation., G5698621524, G5977900945, G6122222817, G6722183715, DEVELOPMENT AND USE OF RELEVANT HAMSTER AND MOUSE SARS-COV-2 INFECTION MODELS TO AID IN THE DESIGN OF THERAPEUTIC AND PROPHYLACTIC OPTIONS FOR COVID-19, Cardiac resident macrophages versus recruited macrophages – developing targets to take advantage of their opposing roles in heart failure., G7864614722, G7905289576, Swift COronavirus therapeutics REsponse
OpenAlex ID: W4306385427