The expression level of angiotensin-converting enzyme 2 determines the severity of COVID-19: lung and heart tissue as targets

Abstract

Researchers have reported some useful information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to CoV disease 2019 (COVID-19). Several studies have been performed in order to develop antiviral drugs, from which a few have been prescribed to patients. Also, several diagnostic tests have been designed to accelerate the process of identifying and treating COVID-19. It has been well-documented that the surface of host cells is covered by some receptors, known as angiotensin-converting enzyme 2 (ACE2), which mediates the binding and entry of CoV. After entering, the viral RNA interrupts the cell proliferation system to activate self-proliferation. However, having all the information about the outbreakof the SARS-COV-2, it is not still clear which factors determine the severity of lung and heart function impairment induced by COVID-19. A major step in exploring SARS-COV-2 pathogenesis is to determine the distribution of ACE2 in different tissues . In this review, the structure and origin of CoV, the role of ACE2 as a receptor of SARS-COV-2 on the surface of host cells, and the ACE2 distribution in different tissues with a focus on lung and cardiovascular system have been discussed. It was also revealed that acute and chronic cardiovascular diseases (CVDs) may result in the clinical severity of COVID-19. In conclusion, this review may provide useful information in developing some promising strategies to end up with a worldwide COVID-19 pandemic.Communicated by Ramaswamy H. Sarma.

Keywords: ACE2; COVID-19; Coronavirus; MERS; SARS; SARS-CoV-2; heart; lung.

Figure 1.

a The structure of human ACE2 after interaction with SARS-CoV-2 S protein (Wang, Zhang, et al., 2020). b Single-cell map of human lung cells expressing ACE-2 (Zhao et al., 2020). Reprinted with permission from Refs. (Wang, Zhang, et al., ; Zhao et al., 2020). Abbreviation: tSNE: t-distributed Stochastic Neighbor Embedding.

Figure 2.

A: ACE2 expression pattern in different organs. a ACE2 expression from TCGA dataset. b ACE2 expression from FANTOM5 CAGE dataset. c ACE2 expression from TCGA in different oral cavity. d ACE2 expression in two kinds of oral sites and others (Xu, Zhong, et al., 2020). B: ACE2 expression pattern in human testes. a ACE2 expression in different cell types. b TMPRSS2 expression in different cells (Wang & Xu, 2020). C: SARS-CoV-2 infection-related susceptible organs, Red: high risk, Grey: low-risk (Zou et al., 2020). Reprinted with permission from Refs. (Wang & Xu, ; Xu, Zhong, et al., ; Zou et al., 2020). Abbreviations: TCGA: The Cancer Genome Atlas; FANTOM5 CAGE: Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression; SPG: spermatogonia; TMPRSS2: transmembrane serine protease 2.