Endocrine Significance of SARS-CoV-2's Reliance on ACE2

Abstract

The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS-2; diabetes; renin-angiotensin system.

Figure 1.

Patterns of gene expression for ACE2 and TMPRSS2 across select human tissues and pancreatic islet cells. (A) Scatter plots showing mRNA expression in various human male and female tissues. Left panel: ACE2 expression levels; right panel: TMPRSS2 expression levels. Data shown are derived from the human protein atlas and genotype tissue expression project (26-28). (dbGap accession number: phs000424.vN.pN expression data accessed on May 30, 2020.) n = 34-293. Data plotted as mean ± SEM. (B) Top panel: Nonlinear multidimensional projection plotting using uniform maximal approximation projection (UMAP) plots for 5 prominent pancreatic islet single-cell RNAseq datasets. Data integration performed using Seurat’s SCTransform function (29)). Bottom panel: UMAP plot showing cellular subtype distribution of human pancreatic islet cells. Each point in both plots represents the relative transcriptional identity of a single cell. (C) Violin plots showing single cell RNAseq data for mRNA expression across all islet cell types. Data are derived from 4 single-cell RNAseq datasets of human pancreatic islets. Top panel: TMPRSS2 mRNA expression levels; bottom panel: ACE2 mRNA expression levels. n = 31. Shape of violin plots shows the probability density of mRNA expression for each cell type, whereas each point denotes the expression of an individual cell. (D) Violin plots showing single-cell RNAseq data for mRNA expression across human pancreatic islet beta cells (left) and alpha cells (right). Top panels: TMPRSS2 mRNA expression levels; bottom panel: ACE2 mRNA expression levels. GSE81076 (30): n = 5; GSE85241 (31): n = 4; GSE86469 (32): n = 8; E-MTAB-5061 (33): n = 10; GSE84133 (34) n = 4 (total cells across 5 datasets = 14 890). Shape of violin plots shows the probability density of mRNA expression for each cell type, whereas each point denotes the expression of an individual cell. (Data for B-D were accessed on May 28, 2020, and analyzed using the Seurat scRNAseq analysis package (35, 36)). ACE2, angiotensin-converting enzyme 2.