A bioinformatics analysis on the potential role of ACE2 in cardiac impairment of patients with coronavirus disease 2019.

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been characterized as a pandemic around the world. Cardiac complications can occur in patients with COVID-19 and can be fatal in severe cases. Recently, it was reported that SARS-CoV-2 used the angiotensin-converting enzyme 2 (ACE2) as a cellular receptor to gain entry into the host cell. However, whether SARS-CoV-2 can directly infect heart tissues and the potential mechanism of cardiac injury in COVID-19 have not been determined. METHODS: To investigate the expression of ACE2 in heart tissues, we performed a bioinformatic analysis from public databases involving mRNA and protein expression. The correlation between ACE2 expression and virus-related genes was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Gene ontology (GO) and protein-protein interaction (PPI) analyses were performed to explore the roles of ACE2. RESULTS: ACE2 expression in the heart was significantly higher than that in the lung. Compared with the other coronavirus receptors, such as aminopeptidase N (ANPEP) or dipeptidyl peptidase 4 (DPP4), the mRNA and protein expression of ACE2 was increased in the heart. Moreover, the mRNA expression of ACE2 was substantially upregulated in patients with dilated cardiomyopathy. Importantly, the expression of ACE2 was positively correlated with genes that regulate viral reproduction and transmission. The GO and PPI analyses showed that the functions of proteins interacting with ACE2 were significantly enriched in the regulation of the viral process and inflammatory response. CONCLUSIONS: Our study provided bioinformatics evidence that the interaction between SARS-CoV-2 and ACE2 in the heart could contribute to COVID-19-mediated myocardial damage via the virus-induced cytopathic effect, triggering a cardiac inflammatory storm. Therefore, the close monitoring of cardiac function and early clinical intervention may be pivotal to preventing cardiac injury-related mortality in patients with COVID-19.