The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2

Abstract

A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients. Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction. And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition. The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2.

Cells and gene expression programs in the adult human heart

“…Related corona viral infections (SARS and MERS) also had cardiac involvement. Here, we found that expression of the viral receptor ACE2 is higher in pericytes than in CM, as previously reported 87 , but also that neither pericytes nor CM express the protease that prime viral entry, TMPRSS2 . Instead CM and pericytes express CTSB and CTSL , which may also promote viral entry.…”

Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection

“…Cardiac injury may be ischemia-mediated, and the profound inflammatory and hemodynamic impacts seen in COVID-19 have been hypothesized to cause atherosclerotic plaque rupture or oxygen supply-demand mismatch resulting in ischemia (Madjid et al, 2020). Alternatively, cardiac tissue expresses the ACE2 receptor, further suggesting feasibility of direct viral internalization in cardiomyocytes (Chen et al, 2020). Indeed, case studies have raised suspicion for cardiac injury mediated by direct myocardial viral infection and resulting fulminant myocarditis (Hu et al, 2020;Tavazzi et al, 2020;Zeng et al, 2020).…”

Clinical features and management of severe COVID-19: A retrospective study in Wuxi, Jiangsu Province, China

“…However, the mechanism still remains unclear. Chen et al found that SARS-CoV-2 might attack pericytes of human heart, thus causing capillary endothelial cell dysfunction, leading to cardiovascular disease and cardiac injury [29]. Jin et al suggested that gastrointestinal epithelial cells had a high affinity to ACE2, indicating the potential of fecal-oral transmission and the tendency of gastrointestinal symptoms in dissemination [3].…”