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Recent:   

ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

Lee et al., Nature Communications, doi:10.1038/s41467-020-19145-6
Oct 2020  
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In Vitro study showing that ACE2 is highly localized within the motile cilia of airway epithelial cells, potentially representing an initial site of SARS-CoV-2 entry. Authors demonstrate that ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) do not increase ciliary ACE2 expression, indicating that these medications do not enhance susceptibility to SARS-CoV-2 infection. Immunohistochemistry and in situ hybridization techniques revealed ACE2 presence in the cilia across the nasal cavity, trachea, and bronchus, while ACE2 was absent in secretory goblet cells. Patient demographics, including age, sex, and smoking status, did not affect ciliary ACE2 expression.
Lee et al., 28 Oct 2020, peer-reviewed, 39 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperMiscellaneousAll
ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs
Ivan T Lee, Tsuguhisa Nakayama, Chien-Ting Wu, Yury Goltsev, Sizun Jiang, Phillip A Gall, Chun-Kang Liao, Liang-Chun Shih, Christian M Schürch, David R Mcilwain, Pauline Chu, Nicole A Borchard, David Zarabanda, Sachi S Dholakia, Angela Yang, Dayoung Kim, Han Chen, Tomoharu Kanie, Chia-Der Lin, Ming-Hsui Tsai, Katie M Phillips, Raymond Kim, Jonathan B Overdevest, Matthew A Tyler, Carol H Yan, Chih-Feng Lin, Yi-Tsen Lin, Da-Tian Bau, Gregory J Tsay, Zara M Patel, Yung-An Tsou, Alexandar Tzankov, Matthias S Matter, Chih-Jaan Tai, Te-Huei Yeh, Peter H Hwang, Garry P Nolan, Jayakar V Nayak, Peter K Jackson
Nature Communications, doi:10.1038/s41467-020-19145-6
ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs Ivan T
G., and S.J., contributed equally and have the right to list their name first in their CV. Funding and supervision were provided by G.P.N., J.V.N., and P.K.J. All authors reviewed and agreed with the content of this manuscript. Competing interests The authors declare no competing interests.
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Med.'}, { 'key': '19145_CR22', 'doi-asserted-by': 'publisher', 'first-page': '135', 'DOI': '10.1016/j.bbrc.2020.03.044', 'volume': '526', 'author': 'F Qi', 'year': '2020', 'unstructured': 'Qi, F., Qian, S., Zhang, S. & Zhang, Z. Single cell RNA sequencing of 13 ' 'human tissues identify cell types and receptors of human ' 'coronaviruses.\xa0Biochem. Biophys. Res. Commun. 526, 135–140 (2020).', 'journal-title': 'Biochem. Biophys. Res. Commun.'}, { 'key': '19145_CR23', 'doi-asserted-by': 'crossref', 'unstructured': 'Limburg, H. et al. TMPRSS2 is the major activating protease of influenza ' 'a virus in primary human airway cells and influenza b virus in human ' 'type II pneumocytes. J. Virol. 93, e00649-19 (2019).', 'DOI': '10.1128/JVI.00649-19'}, { 'key': '19145_CR24', 'doi-asserted-by': 'crossref', 'unstructured': 'Guo, J., Huang, Z., Lin, L. & Lv, J. Coronavirus Disease 2019 (COVID‐19) ' 'and cardiovascular disease: a viewpoint on the potential influence of ' 'angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers ' 'on onset and severity of severe acute respiratory syndrome coronavirus 2 ' 'infection. J. Am. Heart Assoc. 9, e016219 (2020).', 'DOI': '10.1161/JAHA.120.016219'}, { 'key': '19145_CR25', 'doi-asserted-by': 'publisher', 'first-page': '367', 'DOI': '10.1016/j.virol.2007.04.035', 'volume': '367', 'author': 'W Li', 'year': '2007', 'unstructured': 'Li, W. et al. The S proteins of human coronavirus NL63 and severe acute ' 'respiratory syndrome coronavirus bind overlapping regions of ACE2. ' 'Virology 367, 367–374 (2007).', 'journal-title': 'Virology'}, { 'key': '19145_CR26', 'doi-asserted-by': 'publisher', 'first-page': '1216', 'DOI': '10.1016/j.bbrc.2004.05.114', 'volume': '319', 'author': 'H Hofmann', 'year': '2004', 'unstructured': 'Hofmann, H. et al. Susceptibility to SARS coronavirus S protein-driven ' 'infection correlates with expression of angiotensin converting enzyme 2 ' 'and infection can be blocked by soluble receptor. Biochem. Biophys. Res. ' 'Commun. 319, 1216–1221 (2004).', 'journal-title': 'Biochem. Biophys. Res. Commun.'}, { 'key': '19145_CR27', 'doi-asserted-by': 'publisher', 'first-page': '1653', 'DOI': '10.1093/ntr/ntaa082', 'volume': '22', 'author': 'R Patanavanich', 'year': '2020', 'unstructured': 'Patanavanich, R. & Glantz, S. A. Smoking is associated with COVID-19 ' 'progression: a meta-analysis. Nicotine Tob. Res. 22, 1653–1656 (2020).', 'journal-title': 'Nicotine Tob. Res.'}, { 'key': '19145_CR28', 'doi-asserted-by': 'publisher', 'first-page': '1205', 'DOI': '10.1038/s41591-020-0962-9', 'volume': '26', 'author': 'NG Davies', 'year': '2020', 'unstructured': 'Davies, N. G. et al. Age-dependent effects in the transmission and ' 'control of COVID-19 epidemics. Nat. 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Preprint at\xa0bioRxiv ' 'https://doi.org/10.1101/2020.03.28.013672 (2020).', 'DOI': '10.1101/2020.03.28.013672'}, { 'key': '19145_CR31', 'doi-asserted-by': 'publisher', 'first-page': '102976', 'DOI': '10.1016/j.ebiom.2020.102976', 'volume': '60', 'author': 'ME Ortiz', 'year': '2020', 'unstructured': 'Ortiz, M. E. et al. Heterogeneous expression of the SARS-Coronavirus-2 ' 'receptor ACE2 in the human respiratory tract. EBioMedicine 60, 102976 ' '(2020).', 'journal-title': 'EBioMedicine'}, { 'key': '19145_CR32', 'doi-asserted-by': 'publisher', 'first-page': '114', 'DOI': '10.1016/j.ijcard.2016.04.096', 'volume': '215', 'author': 'P-Y Pai', 'year': '2016', 'unstructured': 'Pai, P.-Y., Muo, C.-H., Sung, F.-C., Ho, H.-C. & Lee, Y.-T. Angiotensin ' 'receptor blockers (ARB) outperform angiotensin-converting enzyme (ACE) ' 'inhibitors on ischemic stroke prevention in patients with hypertension ' 'and diabetes - A real-world population study in Taiwan. Int. J. Cardiol. ' '215, 114–119 (2016).', 'journal-title': 'Int. J. Cardiol.'}, { 'key': '19145_CR33', 'doi-asserted-by': 'crossref', 'unstructured': 'Antunes, M. B. & Cohen, N. A. in Rhinology and Facial Plastic Surgery ' '(eds Stucker, F. J. et al.) 83–90 (Springer, 2009).', 'DOI': '10.1007/978-3-540-74380-4_6'}, { 'key': '19145_CR34', 'doi-asserted-by': 'publisher', 'first-page': '817', 'DOI': '10.1161/HYPERTENSIONAHA.119.13382', 'volume': '74', 'author': 'JJ Reho', 'year': '2019', 'unstructured': 'Reho, J. J., Guo, D.-F., Morgan, D. A. & Rahmouni, K. Smooth muscle ' 'cell–specific disruption of the BBSome causes vascular dysfunction. ' 'Hypertension 74, 817–825 (2019).', 'journal-title': 'Hypertension'}, { 'key': '19145_CR35', 'doi-asserted-by': 'publisher', 'first-page': '15511', 'DOI': '10.1128/JVI.79.24.15511-15524.2005', 'volume': '79', 'author': 'AC Sims', 'year': '2005', 'unstructured': 'Sims, A. C. et al. Severe acute respiratory syndrome coronavirus ' 'infection of human ciliated airway epithelia: role of ciliated cells in ' 'viral spread in the conducting airways of the lungs. J. Virol. 79, ' '15511–15524 (2005).', 'journal-title': 'J. Virol.'}, { 'key': '19145_CR36', 'doi-asserted-by': 'crossref', 'unstructured': 'Widagdo, W. et al. Species-specific colocalization of middle east ' 'respiratory syndrome coronavirus attachment and entry receptors. J. ' 'Virol. 93, e00107-19 (2019).', 'DOI': '10.1128/JVI.00107-19'}, { 'key': '19145_CR37', 'doi-asserted-by': 'publisher', 'first-page': '5654', 'DOI': '10.1128/JVI.76.11.5654-5666.2002', 'volume': '76', 'author': 'L Zhang', 'year': '2002', 'unstructured': 'Zhang, L., Peeples, M. E., Boucher, R. C., Collins, P. L. & Pickles, R. ' 'J. Respiratory syncytial virus infection of human airway epithelial ' 'cells is polarized, specific to ciliated cells, and without obvious ' 'cytopathology. J. Virol. 76, 5654–5666 (2002).', 'journal-title': 'J. Virol.'}, { 'key': '19145_CR38', 'doi-asserted-by': 'publisher', 'first-page': '8060', 'DOI': '10.1128/JVI.00384-06', 'volume': '80', 'author': 'CI Thompson', 'year': '2006', 'unstructured': 'Thompson, C. I., Barclay, W. S., Zambon, M. C. & Pickles, R. J. ' 'Infection of human airway epithelium by human and avian strains of ' 'influenza a virus. J. Virol. 80, 8060–8068 (2006).', 'journal-title': 'J. Virol.'}, { 'key': '19145_CR39', 'doi-asserted-by': 'publisher', 'first-page': '906', 'DOI': '10.1093/infdis/jix640', 'volume': '217', 'author': 'KS Tan', 'year': '2018', 'unstructured': 'Tan, K. S. et al. In vitro model of fully differentiated human nasal ' 'epithelial cells infected with rhinovirus reveals epithelium-initiated ' 'immune responses. J. Infect. Dis. 217, 906–915 (2018).', 'journal-title': 'J. Infect. Dis.'}, { 'key': '19145_CR40', 'doi-asserted-by': 'publisher', 'first-page': '1113', 'DOI': '10.1128/JVI.79.2.1113-1124.2005', 'volume': '79', 'author': 'L Zhang', 'year': '2005', 'unstructured': 'Zhang, L. et al. Infection of ciliated cells by human parainfluenza ' 'virus type 3 in an in vitro model of human airway epithelium. J. Virol. ' '79, 1113–1124 (2005).', 'journal-title': 'J. Virol.'}, { 'key': '19145_CR41', 'doi-asserted-by': 'publisher', 'first-page': 'e0130517', 'DOI': '10.1371/journal.pone.0130517', 'volume': '10', 'author': 'K-I Jeong', 'year': '2015', 'unstructured': 'Jeong, K.-I. et al. CX3CR1 is expressed in differentiated human ciliated ' 'airway cells and co-localizes with respiratory syncytial virus on cilia ' 'in a G protein-dependent manner. 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Med.'}, { 'key': '19145_CR44', 'doi-asserted-by': 'publisher', 'first-page': 'e8157', 'DOI': '10.1371/journal.pone.0008157', 'volume': '4', 'author': 'PL Leopold', 'year': '2009', 'unstructured': 'Leopold, P. L. et al. Smoking is associated with shortened airway cilia. ' 'PLoS ONE 4, e8157 (2009).', 'journal-title': 'PLoS ONE'}, { 'key': '19145_CR45', 'doi-asserted-by': 'publisher', 'first-page': '2441', 'DOI': '10.1056/NEJMoa2008975', 'volume': '382', 'author': 'HR Reynolds', 'year': '2020', 'unstructured': 'Reynolds, H. R. et al. Renin–angiotensin–aldosterone system inhibitors ' 'and risk of Covid-19. N. Engl. J. Med. 382, 2441–2448 (2020).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': '19145_CR46', 'doi-asserted-by': 'publisher', 'first-page': '2431', 'DOI': '10.1056/NEJMoa2006923', 'volume': '382', 'author': 'G Mancia', 'year': '2020', 'unstructured': 'Mancia, G., Rea, F., Ludergnani, M., Apolone, G. & Corrao, G. ' 'Renin–angiotensin–aldosterone system blockers and the risk of Covid-19. ' 'N. Engl. J. Med. 382, 2431–2440 (2020).', 'journal-title': 'N. Engl. J. Med.'}, { 'key': '19145_CR47', 'doi-asserted-by': 'publisher', 'first-page': '168', 'DOI': '10.1001/jama.2020.11301', 'volume': '324', 'author': 'EL Fosbøl', 'year': '2020', 'unstructured': 'Fosbøl, E. L. et al. Association of angiotensin-converting enzyme ' 'inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis ' 'and mortality. JAMA 324, 168–177 (2020).', 'journal-title': 'JAMA'}, { 'key': '19145_CR48', 'doi-asserted-by': 'publisher', 'first-page': '1705', 'DOI': '10.1016/S0140-6736(20)31030-8', 'volume': '395', 'author': 'FJ de Abajo', 'year': '2020', 'unstructured': 'de Abajo, F. J. et al. Use of renin–angiotensin–aldosterone system ' 'inhibitors and risk of COVID-19 requiring admission to hospital: a ' 'case-population study. 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' 'Histopathology 77, 198–209 (2020).', 'journal-title': 'Histopathology'}], 'container-title': 'Nature Communications', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41467-020-19145-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41467-020-19145-6', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41467-020-19145-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 12, 6]], 'date-time': '2022-12-06T01:48:02Z', 'timestamp': 1670291282000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41467-020-19145-6'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 10, 28]]}, 'references-count': 49, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2020, 12]]}}, 'alternative-id': ['19145'], 'URL': 'http://dx.doi.org/10.1038/s41467-020-19145-6', 'relation': { 'has-preprint': [ { 'id-type': 'doi', 'id': '10.1101/2020.05.08.20092866', 'asserted-by': 'object'}]}, 'ISSN': ['2041-1723'], 'subject': [], 'container-title-short': 'Nat Commun', 'published': {'date-parts': [[2020, 10, 28]]}, 'assertion': [ { 'value': '18 May 2020', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '30 September 2020', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '28 October 2020', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'The authors declare no competing interests.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '5453'}
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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