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.
Keywords: ACE, angiotensin converting enzyme; ACE2, angiotensin converting enzyme 2; ARB, angiotensin receptor blocker; BNP, B-type natriuretic peptide; COVID-19, coronavirus disease-2019; EmBx, endomyocardial biopsies; F/NDC, nonischemic dilated cardiomyopathy with heart failure; HFrEF, heart failure with reduced (<0.50) left ventricular ejection fraction; IQR, interquartile range; LOCF, last observation carried forward; LV, left ventricle (ventricular); LVEF, left ventricular ejection fraction; NF, nonfailing; NR, nonresponder; PCR, polymerase chain reaction; R, responder; RAS, renin-angiotensin system; RGD, arginine-glycine-aspartic acid; RNA-Seq, ribonucleic acid sequencing; RV, right ventricle (ventricular); SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; angiotensin converting enzyme 2; coronavirus disease 2019; integrins; mRNA, messenger ribonucleic acid; proteases; ventricular remodeling.
© 2020 The Authors.