Dynamic Regulation of SARS-Cov-2 Binding and Cell Entry Mechanisms in Remodeled Human Ventricular Myocardium

Michael R. Bristow, Lawrence S. Zisman, Natasha L. Altman, Edward M. Gilbert, Brian D. Lowes, Wayne A. Minobe, Dobromir Slavov, Jessica A. Schwisow, Erin M. Rodriguez, Ian A. Carroll, Thomas A. Keuer, Peter M. Buttrick, David P. Kao

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Using serial analysis of myocardial gene expression employing endomyocardial biopsy starting material in a dilated cardiomyopathy cohort, we show that mRNA expression of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) cardiac myocyte receptor ACE2 is up-regulated with remodeling and with reverse remodeling down-regulates into the normal range. The proteases responsible for virus-cell membrane fusion were expressed but not regulated with remodeling. In addition, a new candidate for SARS-CoV-2 cell binding and entry was identified, the integrin encoded by ITGA5. Up-regulation in ACE2 in remodeled left ventricles may explain worse outcomes in patients with coronavirus disease 2019 who have underlying myocardial disorders, and counteracting ACE2 up-regulation is a possible therapeutic approach to minimizing cardiac damage.

Original languageEnglish (US)
Pages (from-to)871-883
Number of pages13
JournalJACC: Basic to Translational Science
Volume5
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • angiotensin converting enzyme 2
  • coronavirus disease 2019
  • integrins
  • proteases
  • ventricular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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