Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection

Brittany D Brumback; Oleksandr Dmytrenko; Ashley N Robinson; Adam L Bailey; Pan Ma; Jing Liu; Stephanie C Hicks; Sherwin Ng; Gang Li; David M Zhang; Catherine E Lipovsky; Chieh-Yu Lin; Michael S Diamond; Kory J Lavine; Stacey L Rentschler

doi:10.1016/j.jacbts.2022.09.001

Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection

JACC Basic Transl Sci. 2023 Feb;8(2):109-120. doi: 10.1016/j.jacbts.2022.09.001. Epub 2022 Sep 14.

Authors

Brittany D Brumback^{1

2}, Oleksandr Dmytrenko¹, Ashley N Robinson¹, Adam L Bailey^{3

4}, Pan Ma¹, Jing Liu¹, Stephanie C Hicks¹, Sherwin Ng¹, Gang Li^{1

2}, David M Zhang¹, Catherine E Lipovsky^{1

5}, Chieh-Yu Lin³, Michael S Diamond^{3

6

7}, Kory J Lavine^{1

3

5}, Stacey L Rentschler^{1

2

5}

Affiliations

¹ Department of Medicine, Cardiovascular Division, Washington University in St. Louis, St. Louis, Missouri, USA.
² Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
⁴ Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
⁵ Department of Developmental Biology, Washington University in St. Louis, St. Louis, Missouri, USA.
⁶ Department of Medicine, Infectious Disease, Washington University School of Medicine, St. Louis, Missouri, USA.
⁷ Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.

Abstract

COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19.

Keywords: ACE2, angiotensin-converting enzyme 2; COVID-19; IFN, interferon; MOI, multiplicity of infection; PDGFRβ, platelet-derived growth factor receptor beta; SARS-CoV-2; cardiovascular disease; pericytes.

Abstract

Grants and funding