ACE2 (Angiotensin-Converting Enzyme 2) and TMPRSS2 (Transmembrane Serine Protease 2) Expression and Localization of SARS-CoV-2 Infection in the Human Heart
Atsushi Sakamoto, Rika Kawakami, Kenji Kawai, Andrea Gianatti, Dario Pellegrini, Robert Kutys, Liang Guo, Masayuki Mori, Anne Cornelissen, Yu Sato, Antonio Bellasi, Lara Faggi, Charles C. Hong, Maria Romero, Giulio Guagliumi, Renu Virmani, Aloke V. Finn
Abstract
t least 20% of patients hospitalized with coronavirus disease 2019 (COVID-19) have evidence of cardiac injury and its presence increases mortality. 1ACE 2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) facilitate SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) viral infection.Although ACE2 is expressed in the respiratory epithelium, cardiac tropism for SARS-CoV-2 remains uncertain.Several reports have assessed ACE2 and TMPRSS2 expression by RNA sequencing of normal and diseased hearts 2,3 and reported that ACE2 expression was the highest in pericytes, but it was also appreciable in other cell types including cardiomyocytes, suggesting the heart may be a target for SARS-CoV-2 infection.To understand which cells in the heart are the most likely targets for infection, immunostaining for ACE2 and TMPRSS2, real-time polymerase chain reaction, and in-situ hybridization (ISH) of hearts from 15 COVID-19 victims from Bergamo, Italy was conducted.Control normal hearts, dilated cardiomyopathy, and viral myocarditis hearts (non-COVID-19) were selected from CVPath registry.The study was approved by the ethical committee at Ospedale Papa Giovanni XXIII and CVPath.Anti-ACE2 (R&D), anti-TMPRSS2 (SantaCruz), anti-CD31, anti-CD146, and anti-Connexin-43 (all Abcam) antibodies Downloaded from http://ahajournals.org