Tags

Type your tag names separated by a space and hit enter

Dysbalance of ACE2 levels - a possible cause for severe COVID-19 outcome in COPD.
J Pathol Clin Res. 2021 09; 7(5):446-458.JP

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to healthcare systems worldwide. Binding of the virus to angiotensin-converting enzyme 2 (ACE2) is an important step in the infection mechanism. However, it is unknown if ACE2 expression in patients with chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary arterial hypertension (IPAH), or pulmonary fibrosis (PF), is changed as compared to controls. We used lung samples from patients with COPD (n = 28), IPAH (n = 10), and PF (n = 10) as well as healthy control donor (n = 10) tissue samples to investigate the expression of ACE2 and related cofactors that might influence the course of SARS-CoV-2 infection. Expression levels of the ACE2 receptor, the putative receptor CD147/BSG, and the viral entry cofactors TMPRSS2 (transmembrane serine protease 2), EZR, and FURIN were determined by quantitative PCR and in open-access RNA sequencing datasets. Immunohistochemical and single-cell RNA sequencing (scRNAseq) analyses were used for localization and coexpression, respectively. Soluble ACE2 (sACE2) plasma levels were analyzed by enzyme-linked immunosorbent assay. In COPD as compared to donor, IPAH, and PF lung tissue, gene expression of ACE2, TMPRSS2, and EZR was significantly elevated, but circulating sACE2 levels were significantly reduced in COPD and PF plasma compared to healthy control and IPAH plasma samples. Lung tissue expressions of FURIN and CD147/BSG were downregulated in COPD. None of these changes were associated with changes in pulmonary hemodynamics. Histological analysis revealed coexpression of ACE2, TMPRSS2, and Ezrin in bronchial regions and epithelial cells. This was confirmed by scRNAseq analysis. There were no significant expression changes of the analyzed molecules in the lung tissue of IPAH and idiopathic PF as compared to control. In conclusion, we reveal increased ACE2 and TMPRSS2 expression in lung tissue with a concomitant decrease of protective sACE2 in COPD patients. These changes represent the possible risk factors for an increased susceptibility of COPD patients to SARS-CoV-2 infection.

Authors+Show Affiliations

Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.Division of Pulmonology, Medical University of Graz, Graz, Austria.Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria. Otto Loewi Research Center, Medical University of Graz, Graz, Austria.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33978304

Citation

Flieβer, Elisabeth, et al. "Dysbalance of ACE2 Levels - a Possible Cause for Severe COVID-19 Outcome in COPD." The Journal of Pathology. Clinical Research, vol. 7, no. 5, 2021, pp. 446-458.
Flieβer E, Birnhuber A, Marsh LM, et al. Dysbalance of ACE2 levels - a possible cause for severe COVID-19 outcome in COPD. J Pathol Clin Res. 2021;7(5):446-458.
Flieβer, E., Birnhuber, A., Marsh, L. M., Gschwandtner, E., Klepetko, W., Olschewski, H., & Kwapiszewska, G. (2021). Dysbalance of ACE2 levels - a possible cause for severe COVID-19 outcome in COPD. The Journal of Pathology. Clinical Research, 7(5), 446-458. https://doi.org/10.1002/cjp2.224
Flieβer E, et al. Dysbalance of ACE2 Levels - a Possible Cause for Severe COVID-19 Outcome in COPD. J Pathol Clin Res. 2021;7(5):446-458. PubMed PMID: 33978304.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dysbalance of ACE2 levels - a possible cause for severe COVID-19 outcome in COPD. AU - Flieβer,Elisabeth, AU - Birnhuber,Anna, AU - Marsh,Leigh M, AU - Gschwandtner,Elisabeth, AU - Klepetko,Walter, AU - Olschewski,Horst, AU - Kwapiszewska,Grazyna, Y1 - 2021/05/12/ PY - 2021/03/22/revised PY - 2021/02/15/received PY - 2021/04/21/accepted PY - 2021/5/13/pubmed PY - 2021/8/28/medline PY - 2021/5/12/entrez KW - ACE2 KW - COPD KW - COVID-19 KW - SARS-CoV-2 KW - TMPRSS2 KW - chronic lung disease KW - chronic obstructive pulmonary disease KW - pulmonary fibrosis KW - pulmonary hypertension SP - 446 EP - 458 JF - The journal of pathology. Clinical research JO - J Pathol Clin Res VL - 7 IS - 5 N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to healthcare systems worldwide. Binding of the virus to angiotensin-converting enzyme 2 (ACE2) is an important step in the infection mechanism. However, it is unknown if ACE2 expression in patients with chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary arterial hypertension (IPAH), or pulmonary fibrosis (PF), is changed as compared to controls. We used lung samples from patients with COPD (n = 28), IPAH (n = 10), and PF (n = 10) as well as healthy control donor (n = 10) tissue samples to investigate the expression of ACE2 and related cofactors that might influence the course of SARS-CoV-2 infection. Expression levels of the ACE2 receptor, the putative receptor CD147/BSG, and the viral entry cofactors TMPRSS2 (transmembrane serine protease 2), EZR, and FURIN were determined by quantitative PCR and in open-access RNA sequencing datasets. Immunohistochemical and single-cell RNA sequencing (scRNAseq) analyses were used for localization and coexpression, respectively. Soluble ACE2 (sACE2) plasma levels were analyzed by enzyme-linked immunosorbent assay. In COPD as compared to donor, IPAH, and PF lung tissue, gene expression of ACE2, TMPRSS2, and EZR was significantly elevated, but circulating sACE2 levels were significantly reduced in COPD and PF plasma compared to healthy control and IPAH plasma samples. Lung tissue expressions of FURIN and CD147/BSG were downregulated in COPD. None of these changes were associated with changes in pulmonary hemodynamics. Histological analysis revealed coexpression of ACE2, TMPRSS2, and Ezrin in bronchial regions and epithelial cells. This was confirmed by scRNAseq analysis. There were no significant expression changes of the analyzed molecules in the lung tissue of IPAH and idiopathic PF as compared to control. In conclusion, we reveal increased ACE2 and TMPRSS2 expression in lung tissue with a concomitant decrease of protective sACE2 in COPD patients. These changes represent the possible risk factors for an increased susceptibility of COPD patients to SARS-CoV-2 infection. SN - 2056-4538 UR - https://www.unboundmedicine.com/medline/citation/33978304/Dysbalance_of_ACE2_levels___a_possible_cause_for_severe_COVID_19_outcome_in_COPD_ DB - PRIME DP - Unbound Medicine ER -