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Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation

Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out...

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Autores principales: Baker, Steven Andrew, Kwok, Shirley, Berry, Gerald J., Montine, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886150/
https://www.ncbi.nlm.nih.gov/pubmed/33592054
http://dx.doi.org/10.1371/journal.pone.0247060
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author Baker, Steven Andrew
Kwok, Shirley
Berry, Gerald J.
Montine, Thomas J.
author_facet Baker, Steven Andrew
Kwok, Shirley
Berry, Gerald J.
Montine, Thomas J.
author_sort Baker, Steven Andrew
collection PubMed
description Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010–2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40–83 years old in the ventilated cohort and 14–80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly.
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spelling pubmed-78861502021-02-23 Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation Baker, Steven Andrew Kwok, Shirley Berry, Gerald J. Montine, Thomas J. PLoS One Research Article Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010–2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40–83 years old in the ventilated cohort and 14–80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly. Public Library of Science 2021-02-16 /pmc/articles/PMC7886150/ /pubmed/33592054 http://dx.doi.org/10.1371/journal.pone.0247060 Text en © 2021 Baker et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Baker, Steven Andrew
Kwok, Shirley
Berry, Gerald J.
Montine, Thomas J.
Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
title Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
title_full Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
title_fullStr Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
title_full_unstemmed Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
title_short Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation
title_sort angiotensin-converting enzyme 2 (ace2) expression increases with age in patients requiring mechanical ventilation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886150/
https://www.ncbi.nlm.nih.gov/pubmed/33592054
http://dx.doi.org/10.1371/journal.pone.0247060
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