Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome

Rationale: ACE2 (angiotensin-converting enzyme 2), the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is expressed in type 2 alveolar epithelial cells (AT2) that may play key roles in postinjury repair. An imbalance between ACE2 and ACE has also been hypothesized to...

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Veröffentlicht in:American journal of respiratory and critical care medicine 2021-11, Vol.204 (9), p.1024-1034
Hauptverfasser: Gerard, Ludovic, Lecocq, Marylene, Bouzin, Caroline, Hoton, Delphine, Schmit, Gregory, Pereira, Joao Pinto, Montiel, Virginie, Plante-Bordeneuve, Thomas, Laterre, Pierre-François, Pilette, Charles
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container_end_page 1034
container_issue 9
container_start_page 1024
container_title American journal of respiratory and critical care medicine
container_volume 204
creator Gerard, Ludovic
Lecocq, Marylene
Bouzin, Caroline
Hoton, Delphine
Schmit, Gregory
Pereira, Joao Pinto
Montiel, Virginie
Plante-Bordeneuve, Thomas
Laterre, Pierre-François
Pilette, Charles
description Rationale: ACE2 (angiotensin-converting enzyme 2), the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is expressed in type 2 alveolar epithelial cells (AT2) that may play key roles in postinjury repair. An imbalance between ACE2 and ACE has also been hypothesized to contribute to lung injury. Objectives: To characterize the expression and distribution of ACE2 and ACE and to compare AT2 with endothelial cell expression in coronavirus disease (COVID-19)-related or -unrelated acute respiratory distress syndrome (ARDS) and controls. Methods: Lung tissue stainings (using multiplex immunofluorescence) and serum concentrations of ACEs were determined retrospectively in two different cohorts of patients. AT2 and endothelial cells were stained in lung tissue for ProSPC (pro-surfactant protein C) and CD31, respectively. Measurements and Main Results: Pulmonary ACE2 expression was increased in patients with COVID-19-related and -unrelated ARDS (0.06% of tissue area and 0.12% vs. 0.006% for control subjects; P = 0.013 and P < 0.0001, respectively). ACE2 was upregulated in endothelial cells (0.32% and 0.53% vs. 0.01%; P = 0.009 and P < 0.0001) but not in AT2 cells (0.13% and 0.08% vs. 0.03%; P = 0.94 and P = 0.44). Pulmonary expression of ACE was decreased in both COVID-19-related and -unrelated ARDS (P = 0.057 and P = 0.032). Similar increases in ACE2 and decreases in ACE were observed in sera of COVID-19 (P = 0.0054 and P < 0.0001) and non-COVID-19 ARDS (P < 0.0001 and P = 0.016). In addition, AT2 cells were decreased in patients with COVID-19-related ARDS compared with COVID-19-unrelated ARDS (1.395% vs. 2.94%, P = 0.0033). Conclusions: ACE2 is upregulated in lung tissue and serum of both COVID-19-related and -unrelated ARDS, whereas a loss of AT2 cells is selectively observed in COVID-19-related ARDS.
doi_str_mv 10.1164/rccm.202012-4461OC
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An imbalance between ACE2 and ACE has also been hypothesized to contribute to lung injury. Objectives: To characterize the expression and distribution of ACE2 and ACE and to compare AT2 with endothelial cell expression in coronavirus disease (COVID-19)-related or -unrelated acute respiratory distress syndrome (ARDS) and controls. Methods: Lung tissue stainings (using multiplex immunofluorescence) and serum concentrations of ACEs were determined retrospectively in two different cohorts of patients. AT2 and endothelial cells were stained in lung tissue for ProSPC (pro-surfactant protein C) and CD31, respectively. Measurements and Main Results: Pulmonary ACE2 expression was increased in patients with COVID-19-related and -unrelated ARDS (0.06% of tissue area and 0.12% vs. 0.006% for control subjects; P = 0.013 and P &lt; 0.0001, respectively). ACE2 was upregulated in endothelial cells (0.32% and 0.53% vs. 0.01%; P = 0.009 and P &lt; 0.0001) but not in AT2 cells (0.13% and 0.08% vs. 0.03%; P = 0.94 and P = 0.44). Pulmonary expression of ACE was decreased in both COVID-19-related and -unrelated ARDS (P = 0.057 and P = 0.032). Similar increases in ACE2 and decreases in ACE were observed in sera of COVID-19 (P = 0.0054 and P &lt; 0.0001) and non-COVID-19 ARDS (P &lt; 0.0001 and P = 0.016). In addition, AT2 cells were decreased in patients with COVID-19-related ARDS compared with COVID-19-unrelated ARDS (1.395% vs. 2.94%, P = 0.0033). Conclusions: ACE2 is upregulated in lung tissue and serum of both COVID-19-related and -unrelated ARDS, whereas a loss of AT2 cells is selectively observed in COVID-19-related ARDS.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.202012-4461OC</identifier><identifier>PMID: 34449302</identifier><language>eng</language><publisher>New York: American Thoracic Society</publisher><subject>Cells ; COVID-19 ; Enzymes ; Original ; Respiratory diseases ; Respiratory distress syndrome ; Studies</subject><ispartof>American journal of respiratory and critical care medicine, 2021-11, Vol.204 (9), p.1024-1034</ispartof><rights>Copyright American Thoracic Society Nov 1, 2021</rights><rights>Copyright © 2021 by the American Thoracic Society 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-c287f9c9c1a5ae2dcf618352f34a6167dbf47d19590adc22a517349e7277cf63</citedby><cites>FETCH-LOGICAL-c473t-c287f9c9c1a5ae2dcf618352f34a6167dbf47d19590adc22a517349e7277cf63</cites><orcidid>0000-0002-8842-6270</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,4011,27901,27902</link.rule.ids></links><search><creatorcontrib>Gerard, Ludovic</creatorcontrib><creatorcontrib>Lecocq, Marylene</creatorcontrib><creatorcontrib>Bouzin, Caroline</creatorcontrib><creatorcontrib>Hoton, Delphine</creatorcontrib><creatorcontrib>Schmit, Gregory</creatorcontrib><creatorcontrib>Pereira, Joao Pinto</creatorcontrib><creatorcontrib>Montiel, Virginie</creatorcontrib><creatorcontrib>Plante-Bordeneuve, Thomas</creatorcontrib><creatorcontrib>Laterre, Pierre-François</creatorcontrib><creatorcontrib>Pilette, Charles</creatorcontrib><title>Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome</title><title>American journal of respiratory and critical care medicine</title><description>Rationale: ACE2 (angiotensin-converting enzyme 2), the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is expressed in type 2 alveolar epithelial cells (AT2) that may play key roles in postinjury repair. An imbalance between ACE2 and ACE has also been hypothesized to contribute to lung injury. Objectives: To characterize the expression and distribution of ACE2 and ACE and to compare AT2 with endothelial cell expression in coronavirus disease (COVID-19)-related or -unrelated acute respiratory distress syndrome (ARDS) and controls. Methods: Lung tissue stainings (using multiplex immunofluorescence) and serum concentrations of ACEs were determined retrospectively in two different cohorts of patients. AT2 and endothelial cells were stained in lung tissue for ProSPC (pro-surfactant protein C) and CD31, respectively. Measurements and Main Results: Pulmonary ACE2 expression was increased in patients with COVID-19-related and -unrelated ARDS (0.06% of tissue area and 0.12% vs. 0.006% for control subjects; P = 0.013 and P &lt; 0.0001, respectively). ACE2 was upregulated in endothelial cells (0.32% and 0.53% vs. 0.01%; P = 0.009 and P &lt; 0.0001) but not in AT2 cells (0.13% and 0.08% vs. 0.03%; P = 0.94 and P = 0.44). Pulmonary expression of ACE was decreased in both COVID-19-related and -unrelated ARDS (P = 0.057 and P = 0.032). Similar increases in ACE2 and decreases in ACE were observed in sera of COVID-19 (P = 0.0054 and P &lt; 0.0001) and non-COVID-19 ARDS (P &lt; 0.0001 and P = 0.016). In addition, AT2 cells were decreased in patients with COVID-19-related ARDS compared with COVID-19-unrelated ARDS (1.395% vs. 2.94%, P = 0.0033). Conclusions: ACE2 is upregulated in lung tissue and serum of both COVID-19-related and -unrelated ARDS, whereas a loss of AT2 cells is selectively observed in COVID-19-related ARDS.</description><subject>Cells</subject><subject>COVID-19</subject><subject>Enzymes</subject><subject>Original</subject><subject>Respiratory diseases</subject><subject>Respiratory distress syndrome</subject><subject>Studies</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpdkc9q3DAQh0VpadJtX6AnQS-9ONE_W6tLYXHS1LCwkC6lN6HI462CLW0le8E95dQXyBvmSaplQ6E9adB8fMzMD6H3lFxQWonLaO1wwQgjlBVCVHRTv0DntORlIZQkL3NNJM8d9f0MvUnpnmRwSclrdMZF_uWEnaPfjbcRTIIWr_zOhRF8cr6ogz9AHJ3f4Wv_ax4AM2x8i9chJRw6vOoPEHoT8XbeA24aXEPfJ-w8rjffmquCqqeHxwi9GY9iO42AbyHtXTRjiDO-cmmMkFVfZ9_GMMBb9KozfYJ3z-8CbT9fb-svxXpz09SrdWGF5GNh2VJ2yipLTWmAtbar6JKXrOPCVLSS7V0nZEtVqYhpLWOmpJILBZJJmVm-QJ9O2v10N0BrwY_R9Hof3WDirINx-t-Odz_0Lhz0sqp4vl4WfHwWxPBzgjTqwSWbdzcewpQ0K6uK8AyKjH74D70PU_R5u0wpTpUQefYFYifKxnzaCN3fYSjRx5T1MWV9SlmfUuZ_AKOhnA0</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Gerard, Ludovic</creator><creator>Lecocq, Marylene</creator><creator>Bouzin, Caroline</creator><creator>Hoton, Delphine</creator><creator>Schmit, Gregory</creator><creator>Pereira, Joao Pinto</creator><creator>Montiel, Virginie</creator><creator>Plante-Bordeneuve, Thomas</creator><creator>Laterre, Pierre-François</creator><creator>Pilette, Charles</creator><general>American Thoracic Society</general><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8842-6270</orcidid></search><sort><creationdate>20211101</creationdate><title>Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome</title><author>Gerard, Ludovic ; Lecocq, Marylene ; Bouzin, Caroline ; Hoton, Delphine ; Schmit, Gregory ; Pereira, Joao Pinto ; Montiel, Virginie ; Plante-Bordeneuve, Thomas ; Laterre, Pierre-François ; Pilette, Charles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-c287f9c9c1a5ae2dcf618352f34a6167dbf47d19590adc22a517349e7277cf63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cells</topic><topic>COVID-19</topic><topic>Enzymes</topic><topic>Original</topic><topic>Respiratory diseases</topic><topic>Respiratory distress syndrome</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gerard, Ludovic</creatorcontrib><creatorcontrib>Lecocq, Marylene</creatorcontrib><creatorcontrib>Bouzin, Caroline</creatorcontrib><creatorcontrib>Hoton, Delphine</creatorcontrib><creatorcontrib>Schmit, Gregory</creatorcontrib><creatorcontrib>Pereira, Joao Pinto</creatorcontrib><creatorcontrib>Montiel, Virginie</creatorcontrib><creatorcontrib>Plante-Bordeneuve, Thomas</creatorcontrib><creatorcontrib>Laterre, Pierre-François</creatorcontrib><creatorcontrib>Pilette, Charles</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gerard, Ludovic</au><au>Lecocq, Marylene</au><au>Bouzin, Caroline</au><au>Hoton, Delphine</au><au>Schmit, Gregory</au><au>Pereira, Joao Pinto</au><au>Montiel, Virginie</au><au>Plante-Bordeneuve, Thomas</au><au>Laterre, Pierre-François</au><au>Pilette, Charles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><date>2021-11-01</date><risdate>2021</risdate><volume>204</volume><issue>9</issue><spage>1024</spage><epage>1034</epage><pages>1024-1034</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>Rationale: ACE2 (angiotensin-converting enzyme 2), the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is expressed in type 2 alveolar epithelial cells (AT2) that may play key roles in postinjury repair. An imbalance between ACE2 and ACE has also been hypothesized to contribute to lung injury. Objectives: To characterize the expression and distribution of ACE2 and ACE and to compare AT2 with endothelial cell expression in coronavirus disease (COVID-19)-related or -unrelated acute respiratory distress syndrome (ARDS) and controls. Methods: Lung tissue stainings (using multiplex immunofluorescence) and serum concentrations of ACEs were determined retrospectively in two different cohorts of patients. AT2 and endothelial cells were stained in lung tissue for ProSPC (pro-surfactant protein C) and CD31, respectively. Measurements and Main Results: Pulmonary ACE2 expression was increased in patients with COVID-19-related and -unrelated ARDS (0.06% of tissue area and 0.12% vs. 0.006% for control subjects; P = 0.013 and P &lt; 0.0001, respectively). ACE2 was upregulated in endothelial cells (0.32% and 0.53% vs. 0.01%; P = 0.009 and P &lt; 0.0001) but not in AT2 cells (0.13% and 0.08% vs. 0.03%; P = 0.94 and P = 0.44). Pulmonary expression of ACE was decreased in both COVID-19-related and -unrelated ARDS (P = 0.057 and P = 0.032). Similar increases in ACE2 and decreases in ACE were observed in sera of COVID-19 (P = 0.0054 and P &lt; 0.0001) and non-COVID-19 ARDS (P &lt; 0.0001 and P = 0.016). In addition, AT2 cells were decreased in patients with COVID-19-related ARDS compared with COVID-19-unrelated ARDS (1.395% vs. 2.94%, P = 0.0033). Conclusions: ACE2 is upregulated in lung tissue and serum of both COVID-19-related and -unrelated ARDS, whereas a loss of AT2 cells is selectively observed in COVID-19-related ARDS.</abstract><cop>New York</cop><pub>American Thoracic Society</pub><pmid>34449302</pmid><doi>10.1164/rccm.202012-4461OC</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8842-6270</orcidid><oa>free_for_read</oa></addata></record>
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source American Thoracic Society (ATS) Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Cells
COVID-19
Enzymes
Original
Respiratory diseases
Respiratory distress syndrome
Studies
title Increased Angiotensin-Converting Enzyme 2 and Loss of Alveolar Type II Cells in COVID-19–related Acute Respiratory Distress Syndrome
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