{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:50:28Z","timestamp":1786981828490,"version":"build-2736575974"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary","award":["ED_18-1-2019-0028"],"award-info":[{"award-number":["ED_18-1-2019-0028"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["GINOP-2.3.2-15-2016-00043"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00043"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","award":["GINOP-2.3.2-15-2016-00050"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00050"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"crossref","award":["EFOP-3.6.2-16-2017-00006"],"award-info":[{"award-number":["EFOP-3.6.2-16-2017-00006"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["FK 128809"],"award-info":[{"award-number":["FK 128809"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["K 116940"],"award-info":[{"award-number":["K 116940"]}]},{"name":"National Research, Development and Innovation Fund of Hungary","award":["K 132623"],"award-info":[{"award-number":["K 132623"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin-converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals. About 4 times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (88.3\u2009\u00b1\u200961.6.,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009111, 20.6\u2009\u00b1\u200913.4,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009540, and 16.1\u2009\u00b1\u20097.4\u00a0mU\/L,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200946, respectively). Patients with severe AS were older than patients with hypertension (80\u2009\u00b1\u20096\u00a0years vs. 60\u2009\u00b1\u200915\u00a0years,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05). Serum ACE2 activity correlated negatively with the left ventricular ejection fraction, aortic root area, TAPSE, and positively with the right ventricular systolic pressure, cardiac diameters in patients with AS. In contrast, circulating ACE2 activity was independent of the blood pressure, peak flow velocity at the aortic root, kidney function (GFR), and inflammatory state (CRP). We found no effect of RAAS inhibitory drugs on the serum ACE2 activity in this group of patients. Our results illustrate circulating ACE2 as a potential interface between chronic inflammation, cardiovascular disease, and COVID-19 susceptibility. Elderly patients with AS have markedly elevated ACE2 levels together with altered left and right ventricular functions, which may pose higher risks during COVID-19. Our clinical data do not support a role for RAAS inhibitors in regulating circulating ACE2 levels.\n                  <\/jats:p>","DOI":"10.1007\/s11357-020-00300-2","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T23:45:06Z","timestamp":1611099906000},"page":"19-29","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Level of the SARS-CoV-2 receptor ACE2 activity is highly elevated in old-aged patients with aortic stenosis: implications for ACE2 as a biomarker for the severity of COVID-19"],"prefix":"10.1007","volume":"43","author":[{"given":"Mikl\u00f3s","family":"Fagyas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Kert\u00e9sz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivetta M\u00e1nyin\u00e9","family":"Siket","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"B\u00e1nhegyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertalan","family":"Kracsk\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Szegedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Szokol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guszt\u00e1v","family":"Vajda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildik\u00f3","family":"R\u00e1cz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajnalka","family":"Guly\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mi","family":"Szkib\u00e1k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivienn","family":"R\u00e1cz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Csan\u00e1di","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-3653","authenticated-orcid":false,"given":"Attila","family":"T\u00f3th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ndor","family":"Sipka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"300_CR1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.bbrc.2020.02.071","volume":"525","author":"Y Chen","year":"2020","unstructured":"Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020;525:135\u201340. https:\/\/doi.org\/10.1016\/j.bbrc.2020.02.071.","journal-title":"Biochem Biophys Res Commun"},{"key":"300_CR2","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271\u201380. https:\/\/doi.org\/10.1016\/j.cell.2020.02.052 e8.","journal-title":"Cell."},{"key":"300_CR3","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/s41423-020-0400-4","volume":"17","author":"W Tai","year":"2020","unstructured":"Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & Molecular Immunology. 2020;17:613\u201320. https:\/\/doi.org\/10.1038\/s41423-020-0400-4.","journal-title":"Cellular & Molecular Immunology"},{"key":"300_CR4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","volume":"181","author":"AC Walls","year":"2020","unstructured":"Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181:281\u2013292.e6. https:\/\/doi.org\/10.1016\/j.cell.2020.02.058.","journal-title":"Cell."},{"key":"300_CR5","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","volume":"581","author":"J Lan","year":"2020","unstructured":"Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581:215\u201320. https:\/\/doi.org\/10.1038\/s41586-020-2180-5.","journal-title":"Nature."},{"key":"300_CR6","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1056\/NEJMsr2005760","volume":"382","author":"M Vaduganathan","year":"2020","unstructured":"Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382:1653\u20139. https:\/\/doi.org\/10.1056\/NEJMsr2005760.","journal-title":"N Engl J Med"},{"key":"300_CR7","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41569-020-0360-5","volume":"17","author":"YY Zheng","year":"2020","unstructured":"Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17:259\u201360. https:\/\/doi.org\/10.1038\/s41569-020-0360-5.","journal-title":"Nat Rev Cardiol"},{"issue":"4","key":"300_CR8","doi-asserted-by":"publisher","first-page":"e87844","DOI":"10.1371\/journal.pone.0087844","volume":"9","author":"M Fagyas","year":"2014","unstructured":"Fagyas M, Uri K, Siket IM, Fulop GA, Csato V, Darago A, et al. New perspectives in the renin-angiotensin-aldosterone system (RAAS) II: albumin suppresses angiotensin converting enzyme (ACE) activity in human. PLoS One. 2014;9(4):e87844. https:\/\/doi.org\/10.1371\/journal.pone.0087844.","journal-title":"PLoS One"},{"key":"300_CR9","doi-asserted-by":"publisher","unstructured":"Uri K, Fagyas M, Kertesz A, Borbely A, Jenei C, Bene O et al. Circulating ACE2 activity correlates with cardiovascular disease development. Journal of the renin-angiotensin-aldosterone system : JRAAS. 2016;17(4). doi:https:\/\/doi.org\/10.1177\/1470320316668435.","DOI":"10.1177\/1470320316668435"},{"key":"300_CR10","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1001\/jama.2020.5394","volume":"323","author":"G Grasselli","year":"2020","unstructured":"Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region. Italy Jama. 2020;323:1574\u201381. https:\/\/doi.org\/10.1001\/jama.2020.5394.","journal-title":"Italy Jama"},{"issue":"3","key":"300_CR11","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s10753-012-9579-6","volume":"36","author":"N Cote","year":"2013","unstructured":"Cote N, Mahmut A, Bosse Y, Couture C, Page S, Trahan S, et al. Inflammation is associated with the remodeling of calcific aortic valve disease. Inflammation. 2013;36(3):573\u201381. https:\/\/doi.org\/10.1007\/s10753-012-9579-6.","journal-title":"Inflammation."},{"issue":"20","key":"300_CR12","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1161\/CIRCULATIONAHA.120.046941","volume":"141","author":"KJ Clerkin","year":"2020","unstructured":"Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and cardiovascular disease. Circulation. 2020;141(20):1648\u201355. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.120.046941.","journal-title":"Circulation."},{"issue":"4","key":"300_CR13","doi-asserted-by":"publisher","first-page":"e87845","DOI":"10.1371\/journal.pone.0087845","volume":"9","author":"K Uri","year":"2014","unstructured":"Uri K, Fagyas M, Manyine Siket I, Kertesz A, Csanadi Z, Sandorfi G, et al. New perspectives in the renin-angiotensin-aldosterone system (RAAS) IV: circulating ACE2 as a biomarker of systolic dysfunction in human hypertension and heart failure. PLoS One. 2014;9(4):e87845. https:\/\/doi.org\/10.1371\/journal.pone.0087845.","journal-title":"PLoS One"},{"key":"300_CR14","doi-asserted-by":"publisher","unstructured":"Esler M, Esler D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? Journal of Hypertension. 2020;Publish Ahead of Print. doi:https:\/\/doi.org\/10.1097\/hjh.0000000000002450.","DOI":"10.1097\/hjh.0000000000002450"},{"key":"300_CR15","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.atherosclerosis.2018.08.029","volume":"277","author":"KI Cho","year":"2018","unstructured":"Cho KI, Sakuma I, Sohn IS, Jo SH, Koh KK. Inflammatory and metabolic mechanisms underlying the calcific aortic valve disease. Atherosclerosis. 2018;277:60\u20135. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2018.08.029.","journal-title":"Atherosclerosis."},{"issue":"1","key":"300_CR16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/cce2.71","volume":"4","author":"JR Sysol","year":"2018","unstructured":"Sysol JR, Machado RF. Classification and pathophysiology of pulmonary hypertension. Continuing Cardiology Education. 2018;4(1):2\u201312. https:\/\/doi.org\/10.1002\/cce2.71.","journal-title":"Continuing Cardiology Education"},{"issue":"11","key":"300_CR17","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.jacc.2013.05.015","volume":"62","author":"RL Osnabrugge","year":"2013","unstructured":"Osnabrugge RL, Mylotte D, Head SJ, Van Mieghem NM, Nkomo VT, LeReun CM, et al. Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study. J Am Coll Cardiol. 2013;62(11):1002\u201312. https:\/\/doi.org\/10.1016\/j.jacc.2013.05.015.","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"300_CR18","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.jcmg.2019.09.005","volume":"13","author":"J Ramchand","year":"2020","unstructured":"Ramchand J, Patel SK, Kearney LG, Matalanis G, Farouque O, Srivastava PM, et al. Plasma ACE2 activity predicts mortality in aortic stenosis and is associated with severe myocardial fibrosis. JACC Cardiovasc Imaging. 2020;13(3):655\u201364. https:\/\/doi.org\/10.1016\/j.jcmg.2019.09.005.","journal-title":"JACC Cardiovasc Imaging"},{"issue":"19","key":"300_CR19","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1093\/eurheartj\/ehaa373","volume":"41","author":"IE Sama","year":"2020","unstructured":"Sama IE, Ravera A, Santema BT, van Goor H, Ter Maaten JM, Cleland JGF, et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. Eur Heart J. 2020;41(19):1810\u20137. https:\/\/doi.org\/10.1093\/eurheartj\/ehaa373.","journal-title":"Eur Heart J"},{"issue":"3","key":"300_CR20","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1161\/HYPERTENSIONAHA.107.100693","volume":"51","author":"S Der Sarkissian","year":"2008","unstructured":"Der Sarkissian S, Grobe JL, Yuan L, Narielwala DR, Walter GA, Katovich MJ, et al. Cardiac overexpression of angiotensin converting enzyme 2 protects the heart from ischemia-induced pathophysiology. Hypertension. 2008;51(3):712\u20138. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.107.100693.","journal-title":"Hypertension."},{"issue":"10","key":"300_CR21","doi-asserted-by":"publisher","first-page":"H1697","DOI":"10.1152\/ajpheart.00854.2014","volume":"309","author":"N Singh","year":"2015","unstructured":"Singh N, Joshi S, Guo L, Baker MB, Li Y, Castellano RK, et al. ACE2\/Ang-(1-7)\/mas axis stimulates vascular repair-relevant functions of CD34+ cells. Am J Physiol Heart Circ Physiol. 2015;309(10):H1697\u2013707. https:\/\/doi.org\/10.1152\/ajpheart.00854.2014.","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"11","key":"300_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015151","volume":"5","author":"M Maioli","year":"2010","unstructured":"Maioli M, Santaniello S, Montella A, Bandiera P, Cantoni S, Cavallini C, et al. Hyaluronan esters drive Smad gene expression and signaling enhancing cardiogenesis in mouse embryonic and human mesenchymal stem cells. PLoS One. 2010;5(11):e15151. https:\/\/doi.org\/10.1371\/journal.pone.0015151.","journal-title":"PLoS One"},{"key":"300_CR23","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1164\/rccm.202003-0817LE","volume":"201","author":"L Gattinoni","year":"2020","unstructured":"Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. Covid-19 does not lead to a \u201ctypical\u201d acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;201:1299\u2013300. https:\/\/doi.org\/10.1164\/rccm.202003-0817LE.","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"300_CR24","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1042\/cs20200163","volume":"134","author":"D Batlle","year":"2020","unstructured":"Batlle D, Wysocki J, Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clinical science (London, England : 1979). 2020;134(5):543\u20135. https:\/\/doi.org\/10.1042\/cs20200163.","journal-title":"Clinical science (London, England : 1979)"},{"issue":"7047","key":"300_CR25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature03712","volume":"436","author":"Y Imai","year":"2005","unstructured":"Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112\u20136. https:\/\/doi.org\/10.1038\/nature03712.","journal-title":"Nature."},{"key":"300_CR26","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.1016\/s2213-2600(20)30116-8","volume":"8","author":"L Fang","year":"2020","unstructured":"Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;8:e21. https:\/\/doi.org\/10.1016\/s2213-2600(20)30116-8.","journal-title":"Lancet Respir Med"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-020-00300-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-020-00300-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-020-00300-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T09:33:00Z","timestamp":1618479180000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-020-00300-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,20]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["300"],"URL":"https:\/\/doi.org\/10.1007\/s11357-020-00300-2","relation":{},"ISSN":["2509-2715","2509-2723"],"issn-type":[{"value":"2509-2715","type":"print"},{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,20]]},"assertion":[{"value":"1 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}