{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:46Z","timestamp":1760235766422,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>In some subjects with inherited pheochromocytoma\/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1\u03b1) stabilization\/activation could lead to an increase in angiotensin converting enzymes (ACE). This would result in the stimulation of angiotensin (AT) II production and, hence, reduce the availability of ACE 2. The latter would provide decreased numbers of binding sites for the spike protein of SARS-CoV-2 and, therefore, result in less points of viral entry into cells. Thus, subjects with HIF1\u03b1-associated PPG syndromes may benefit from an inherent protective effect against COVID-19. Such an implication of HIF1\u03b1 vis-\u00e0-vis COVID-19 could open ways of therapeutic interventions.<\/jats:p>","DOI":"10.3390\/medicina57101033","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T21:38:09Z","timestamp":1632865089000},"page":"1033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inherited\/Genetically-Associated Pheochromocytoma\/ Paraganglioma Syndromes and COVID-19"],"prefix":"10.3390","volume":"57","author":[{"given":"Ioannis","family":"Ilias","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, \u201cElena Venizelou\u201d Hospital, GR-11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5876-7883","authenticated-orcid":false,"given":"Gregory","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"1st Department of Propaedeutic and Internal Medicine, National and Kapodistrian University of Athens, GR-11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-709X","authenticated-orcid":false,"given":"Konstantinos","family":"Barkas","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, \u201cAgios Panteleimon\u201d General Hospital of Nikaia-Pireas, GR-12351 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, GR-11527 Athens, Greece"},{"name":"UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, GR-11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1080\/17446651.2019.1657007","article-title":"Addressing delays in the diagnosis of pheochromocytoma\/paraganglioma","volume":"14","author":"Ilias","year":"2019","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/S2213-8587(20)30342-9","article-title":"Catecholamine physiology and its implications in patients with COVID-19","volume":"8","author":"Gubbi","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4148","DOI":"10.1158\/1078-0432.CCR-10-0637","article-title":"Mutation of SDHB is a cause of hypoxia-related high-altitude paraganglioma","volume":"16","author":"Figuera","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s12022-020-09658-7","article-title":"What Have We Learned from Molecular Biology of Paragangliomas and Pheochromocytomas?","volume":"32","author":"Papathomas","year":"2021","journal-title":"Endocr. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1056\/NEJMra1612008","article-title":"Physiological Effects of Chronic Hypoxia","volume":"376","author":"West","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"584758","DOI":"10.1155\/2015\/584758","article-title":"Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway?","volume":"2015","author":"Kumar","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1101\/gad.250167.114","article-title":"Human high-altitude adaptation: Forward genetics meets the HIF pathway","volume":"28","author":"Bigham","year":"2014","journal-title":"Genes Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1089\/ham.2010.1099","article-title":"Hypoxia: Adapting to high altitude by mutating EPAS-1, the gene encoding HIF-2\u03b1","volume":"12","author":"Gassmann","year":"2011","journal-title":"High Alt. Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-4419-8997-0_7","article-title":"Hypoxia and high altitude. The molecular response","volume":"543","author":"Ogunshola","year":"2003","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"L631","DOI":"10.1152\/ajplung.90415.2008","article-title":"Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells","volume":"297","author":"Zhang","year":"2009","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Stephens, K.E., Chernyavskiy, P., and Bruns, D.R. (2021). Impact of altitude on COVID-19 infection and death in the United States: A modeling and observational study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0245055"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1089\/ham.2020.0114","article-title":"Lower Incidence of COVID-19 at High Altitude: Facts and Confounders","volume":"21","author":"Pun","year":"2020","journal-title":"High Alt. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103443","DOI":"10.1016\/j.resp.2020.103443","article-title":"Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude?","volume":"277","author":"Dutschmann","year":"2020","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1080\/22221751.2021.1932607","article-title":"Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate","volume":"10","author":"Bosch","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/s41401-020-00554-8","article-title":"Hypoxia, HIF-1\u03b1, and COVID-19: From pathogenic factors to potential therapeutic targets","volume":"41","author":"Serebrovska","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104833","DOI":"10.1016\/j.phrs.2020.104833","article-title":"Physiological and pathological regulation of ACE2, the SARS-CoV-2 receptor","volume":"157","author":"Li","year":"2020","journal-title":"Pharmacol. Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/10\/1033\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:06:26Z","timestamp":1760166386000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/10\/1033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":16,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["medicina57101033"],"URL":"https:\/\/doi.org\/10.3390\/medicina57101033","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2021,9,28]]}}}