{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:24:00Z","timestamp":1791721440045,"version":"4.3.4"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1496\/7-1, KU 1496\/7-3, INST 392\/141-1 FUGG"],"award-info":[{"award-number":["KU 1496\/7-1, KU 1496\/7-3, INST 392\/141-1 FUGG"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004168","name":"Universit\u00e4t zu L\u00fcbeck","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004168","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pflugers Arch - Eur J Physiol"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Proinflammatory cytokines target vascular endothelial cells during COVID-19 infections. In particular, the endothelial glycocalyx (eGC), a proteoglycan-rich layer on top of endothelial cells, was identified as a vulnerable, vasoprotective structure during infections. Thus, eGC damage can be seen as a hallmark in the development of endothelial dysfunction and inflammatory processes. Using sera derived from patients suffering from COVID-19, we could demonstrate that the eGC became progressively worse in relation to disease severity (mild vs severe course) and in correlation to IL-6 levels. This could be prevented by administering low doses of spironolactone, a well-known and highly specific aldosterone receptor antagonist. Our results confirm that SARS-CoV-2 infections cause eGC damage and endothelial dysfunction and we outline the underlying mechanisms and suggest potential therapeutic options.<\/jats:p>","DOI":"10.1007\/s00424-022-02726-3","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T06:02:58Z","timestamp":1658469778000},"page":"1069-1076","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mineralocorticoid receptor-antagonism prevents COVID-19-dependent glycocalyx damage"],"prefix":"10.1007","volume":"474","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5597-5751","authenticated-orcid":false,"given":"Benedikt","family":"Fels","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sovon","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-6267","authenticated-orcid":false,"given":"Carl","family":"Vahldieck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-147X","authenticated-orcid":false,"given":"Tobias","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"K\u00e4ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-1233","authenticated-orcid":false,"given":"Jan","family":"Rupp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3831-1440","authenticated-orcid":false,"given":"Kristina","family":"Kusche-Vihrog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"2726_CR1","doi-asserted-by":"publisher","unstructured":"Lampsas S, Tsaplaris P, Pantelidis P, Oikonomou E, Marinos G, Charalambous G, Souvaliotis N, Mystakidi V-C, Goliopoulou A, Katsianos E, Siasos G, Vavuranakis M-A, Tsioufis C, Vavuranakis M, Tousoulis D 2021 The role of endothelial related circulating biomarkers in COVID-19. A systematic review and meta-analysis. Curr Med Chem. https:\/\/doi.org\/10.2174\/0929867328666211026124033","DOI":"10.2174\/0929867328666211026124033"},{"key":"2726_CR2","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","volume":"395","author":"Z Varga","year":"2020","unstructured":"Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H (2020) Endothelial cell infection and endotheliitis in COVID-19. The Lancet 395:1417\u20131418. https:\/\/doi.org\/10.1016\/S0140-6736(20)30937-5","journal-title":"The Lancet"},{"key":"2726_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.607306","volume":"12","author":"PP Wadowski","year":"2021","unstructured":"Wadowski PP, Jilma B, Kopp CW, Ertl S, Gremmel T, Koppensteiner R (2021) Glycocalyx as possible limiting factor in COVID-19. Front Immunol 12:607306. https:\/\/doi.org\/10.3389\/fimmu.2021.607306","journal-title":"Front Immunol"},{"key":"2726_CR4","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.bj.2020.08.007","volume":"43","author":"M Yamaoka-Tojo","year":"2020","unstructured":"Yamaoka-Tojo M (2020) Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19. Biomed J 43:399\u2013413. https:\/\/doi.org\/10.1016\/j.bj.2020.08.007","journal-title":"Biomed J"},{"key":"2726_CR5","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1007\/s00441-014-1853-5","volume":"355","author":"J Fels","year":"2014","unstructured":"Fels J, Jeggle P, Liashkovich I, Peters W, Oberleithner H (2014) Nanomechanics of vascular endothelium. Cell Tissue Res 355:727\u2013737. https:\/\/doi.org\/10.1007\/s00441-014-1853-5","journal-title":"Cell Tissue Res"},{"key":"2726_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.07.021","author":"ZC Cosgun","year":"2020","unstructured":"Cosgun ZC, Fels B, Kusche-Vihrog K (2020) Nanomechanics of the endothelial glycocalyx: from structure to function. Am J Pathol. https:\/\/doi.org\/10.1016\/j.ajpath.2019.07.021","journal-title":"Am J Pathol"},{"key":"2726_CR7","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1146\/annurev.bioeng.9.060906.151959","volume":"9","author":"S Weinbaum","year":"2007","unstructured":"Weinbaum S, Tarbell JM, Damiano ER (2007) The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng 9:121\u2013167. https:\/\/doi.org\/10.1146\/annurev.bioeng.9.060906.151959","journal-title":"Annu Rev Biomed Eng"},{"key":"2726_CR8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13049-018-0483-4","volume":"26","author":"A Rovas","year":"2018","unstructured":"Rovas A, Lukasz A-H, Vink H, Urban M, Sackarnd J, Pavenst\u00e4dt H, K\u00fcmpers P (2018) Bedside analysis of the sublingual microvascular glycocalyx in the emergency room and intensive care unit - the GlycoNurse study. Scand J Trauma Resusc Emerg Med 26:16. https:\/\/doi.org\/10.1186\/s13049-018-0483-4","journal-title":"Scand J Trauma Resusc Emerg Med"},{"key":"2726_CR9","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s10456-020-09753-7","volume":"24","author":"A Rovas","year":"2021","unstructured":"Rovas A, Osiaevi I, Buscher K, Sackarnd J, Tepasse P-R, Fobker M, K\u00fchn J, Braune S, G\u00f6bel U, Th\u00f6lking G, Gr\u00f6schel A, Pavenst\u00e4dt H, Vink H, K\u00fcmpers P (2021) Microvascular dysfunction in COVID-19: the MYSTIC study. Angiogenesis 24:145\u2013157. https:\/\/doi.org\/10.1007\/s10456-020-09753-7","journal-title":"Angiogenesis"},{"key":"2726_CR10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cytogfr.2020.05.003","volume":"53","author":"F Coperchini","year":"2020","unstructured":"Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M (2020) The cytokine storm in COVID-19: An overview of the involvement of the chemokine\/chemokine-receptor system. Cytokine Growth Factor Rev 53:25\u201332. https:\/\/doi.org\/10.1016\/j.cytogfr.2020.05.003","journal-title":"Cytokine Growth Factor Rev"},{"key":"2726_CR11","doi-asserted-by":"publisher","first-page":"E2315","DOI":"10.3390\/jcm9072315","volume":"9","author":"O Villard","year":"2020","unstructured":"Villard O, Morquin D, Molinari N, Raingeard I, Nagot N, Cristol J-P, Jung B, Roubille C, Foulongne V, Fesler P, Lamure S, Taourel P, Konate A, Maria ATJ, Makinson A, Bertchansky I, Larcher R, Klouche K, Le Moing V, Renard E, Guilpain P (2020) The plasmatic aldosterone and C-reactive protein levels, and the severity of Covid-19: the Dyhor-19 Study. J Clin Med 9:E2315. https:\/\/doi.org\/10.3390\/jcm9072315","journal-title":"J Clin Med"},{"key":"2726_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.575047","volume":"11","author":"B Buijsers","year":"2020","unstructured":"Buijsers B, Yanginlar C, de Nooijer A, Grondman I, Maciej-Hulme ML, Jonkman I, Janssen NAF, Rother N, de Graaf M, Pickkers P, Kox M, Joosten LAB, Nijenhuis T, Netea MG, Hilbrands L, van de Veerdonk FL, Duivenvoorden R, de Mast Q, van der Vlag J (2020) Increased plasma heparanase activity in COVID-19 patients. Front Immunol 11:575047. https:\/\/doi.org\/10.3389\/fimmu.2020.575047","journal-title":"Front Immunol"},{"key":"2726_CR13","doi-asserted-by":"publisher","first-page":"E9712","DOI":"10.3390\/ijms21249712","volume":"21","author":"M Yamaoka-Tojo","year":"2020","unstructured":"Yamaoka-Tojo M (2020) Vascular endothelial glycocalyx damage in COVID-19. Int J Mol Sci 21:E9712. https:\/\/doi.org\/10.3390\/ijms21249712","journal-title":"Int J Mol Sci"},{"key":"2726_CR14","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1186\/s13054-021-03816-x","volume":"25","author":"A Zarbock","year":"2021","unstructured":"Zarbock A, Chawla L, Bellomo R (2021) Why the renin-angiotensin-aldosterone system (RAAS) in critically ill patients can no longer be ignored. Crit Care 25:389. https:\/\/doi.org\/10.1186\/s13054-021-03816-x","journal-title":"Crit Care"},{"key":"2726_CR15","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1016\/j.ijrobp.2008.05.061","volume":"73","author":"CA Hahn","year":"2009","unstructured":"Hahn CA, Zhou S-M, Raynor R, Tisch A, Light K, Shafman T, Wong T, Kirkpatrick J, Turkington T, Hollis D, Marks LB (2009) Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction. Int J Radiat Oncol Biol Phys 73:1082\u20131087. https:\/\/doi.org\/10.1016\/j.ijrobp.2008.05.061","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2726_CR16","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s00063-018-0469-z","volume":"113","author":"A-H Lukasz","year":"2018","unstructured":"Lukasz A-H, K\u00fcmpers P (2018) Angiopoietin-2 regulates endothelial glycocalyx. Med Klin Intensivmed Notfmed 113:497\u2013500. https:\/\/doi.org\/10.1007\/s00063-018-0469-z","journal-title":"Med Klin Intensivmed Notfmed"},{"key":"2726_CR17","doi-asserted-by":"publisher","first-page":"12157","DOI":"10.1038\/s41598-021-91231-1","volume":"11","author":"M Targosz-Korecka","year":"2021","unstructured":"Targosz-Korecka M, Kubisiak A, Kloska D, Kopacz A, Grochot-Przeczek A, Szymonski M (2021) Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors. Sci Rep 11:12157. https:\/\/doi.org\/10.1038\/s41598-021-91231-1","journal-title":"Sci Rep"},{"key":"2726_CR18","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1172\/JCI107470","volume":"52","author":"EA Jaffe","year":"1973","unstructured":"Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52:2745\u20132756. https:\/\/doi.org\/10.1172\/JCI107470","journal-title":"J Clin Invest"},{"key":"2726_CR19","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1007\/s00424-007-0341-0","volume":"455","author":"K Kusche-Vihrog","year":"2008","unstructured":"Kusche-Vihrog K, Sobczak K, Bangel N, Wilhelmi M, Nechyporuk-Zloy V, Schwab A, Schillers H, Oberleithner H (2008) Aldosterone and amiloride alter ENaC abundance in vascular endothelium. Pflugers Arch 455:849\u2013857. https:\/\/doi.org\/10.1007\/s00424-007-0341-0","journal-title":"Pflugers Arch"},{"key":"2726_CR20","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1007\/s00424-011-0999-1","volume":"462","author":"H Oberleithner","year":"2011","unstructured":"Oberleithner H, Peters W, Kusche-Vihrog K, Korte S, Schillers H, Kliche K, Oberleithner K (2011) Salt overload damages the glycocalyx sodium barrier of vascular endothelium. Pflugers Arch 462:519\u2013528. https:\/\/doi.org\/10.1007\/s00424-011-0999-1","journal-title":"Pflugers Arch"},{"key":"2726_CR21","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1093\/cvr\/cvaa230","volume":"116","author":"PC Evans","year":"2020","unstructured":"Evans PC, Rainger GE, Mason JC, Guzik TJ, Osto E, Stamataki Z, Neil D, Hoefer IE, Fragiadaki M, Waltenberger J, Weber C, Bochaton-Piallat M-L, B\u00e4ck M (2020) Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science. Cardiovasc Res 116:2177\u20132184. https:\/\/doi.org\/10.1093\/cvr\/cvaa230","journal-title":"Cardiovasc Res"},{"key":"2726_CR22","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/j.cjco.2021.05.020","volume":"3","author":"RM Touyz","year":"2021","unstructured":"Touyz RM, Boyd MOE, Guzik T, Padmanabhan S, McCallum L, Delles C, Mark PB, Petrie JR, Rios F, Montezano AC, Sykes R, Berry C (2021) Cardiovascular and renal risk factors and complications associated with COVID-19. CJC Open 3:1257\u20131272. https:\/\/doi.org\/10.1016\/j.cjco.2021.05.020","journal-title":"CJC Open"},{"key":"2726_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2022.106975","volume":"144","author":"E Oikonomou","year":"2022","unstructured":"Oikonomou E, Souvaliotis N, Lampsas S, Siasos G, Poulakou G, Theofilis P, Papaioannou TG, Haidich A-B, Tsaousi G, Ntousopoulos V, Sakka V, Charalambous G, Rapti V, Raftopoulou S, Syrigos K, Tsioufis C, Tousoulis D, Vavuranakis M (2022) Endothelial dysfunction in acute and long standing COVID-19: a prospective cohort study. Vascul Pharmacol 144:106975. https:\/\/doi.org\/10.1016\/j.vph.2022.106975","journal-title":"Vascul Pharmacol"},{"key":"2726_CR24","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.1093\/eurheartj\/ehaa623","volume":"41","author":"P Libby","year":"2020","unstructured":"Libby P, L\u00fcscher T (2020) COVID-19 is, in the end, an endothelial disease. Eur Heart J 41:3038\u20133044. https:\/\/doi.org\/10.1093\/eurheartj\/ehaa623","journal-title":"Eur Heart J"},{"key":"2726_CR25","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00424-007-0212-8","volume":"454","author":"S Reitsma","year":"2007","unstructured":"Reitsma S, Slaaf DW, Vink H, van Zandvoort MAMJ, oudeEgbrink MGA, (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 454:345\u2013359. https:\/\/doi.org\/10.1007\/s00424-007-0212-8","journal-title":"Pflugers Arch"},{"key":"2726_CR26","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1186\/1742-2094-9-260","volume":"9","author":"B Chantong","year":"2012","unstructured":"Chantong B, Kratschmar DV, Nashev LG, Balazs Z, Odermatt A (2012) Mineralocorticoid and glucocorticoid receptors differentially regulate NF-kappaB activity and pro-inflammatory cytokine production in murine BV-2 microglial cells. J Neuroinflammation 9:260. https:\/\/doi.org\/10.1186\/1742-2094-9-260","journal-title":"J Neuroinflammation"},{"key":"2726_CR27","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1681\/ASN.2008020232","volume":"20","author":"V Leroy","year":"2009","unstructured":"Leroy V, Seigneux SD, Agassiz V, Hasler U, Rafestin-Oblin M-E, Vinciguerra M, Martin P-Y, F\u00e9raille E (2009) Aldosterone activates NF-\u03baB in the collecting duct. JASN 20:131\u2013144. https:\/\/doi.org\/10.1681\/ASN.2008020232","journal-title":"JASN"},{"key":"2726_CR28","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1007\/s00424-020-02407-z","volume":"472","author":"M Lipphardt","year":"2020","unstructured":"Lipphardt M, Song JW, Goligorsky MS (2020) Sirtuin 1 and endothelial glycocalyx. Pflugers Arch 472:991\u20131002. https:\/\/doi.org\/10.1007\/s00424-020-02407-z","journal-title":"Pflugers Arch"},{"key":"2726_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2021.100097","volume":"13","author":"V Masola","year":"2022","unstructured":"Masola V, Greco N, Gambaro G, Franchi M, Onisto M (2022) Heparanase as active player in endothelial glycocalyx remodeling. Matrix Biol Plus 13:100097. https:\/\/doi.org\/10.1016\/j.mbplus.2021.100097","journal-title":"Matrix Biol Plus"},{"key":"2726_CR30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12959-021-00308-4","volume":"19","author":"F Ogawa","year":"2021","unstructured":"Ogawa F, Oi Y, Nakajima K, Matsumura R, Nakagawa T, Miyagawa T, Sakai K, Saji R, Taniguchi H, Takahashi K, Abe T, Iwashita M, Nishii M, Takeuchi I (2021) Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19. Thromb J 19:55. https:\/\/doi.org\/10.1186\/s12959-021-00308-4","journal-title":"Thromb J"},{"key":"2726_CR31","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12959-021-00258-x","volume":"19","author":"K Suzuki","year":"2021","unstructured":"Suzuki K, Okada H, Tomita H, Sumi K, Kakino Y, Yasuda R, Kitagawa Y, Fukuta T, Miyake T, Yoshida S, Suzuki A, Ogura S (2021) Possible involvement of Syndecan-1 in the state of COVID-19 related to endothelial injury. Thromb J 19:5. https:\/\/doi.org\/10.1186\/s12959-021-00258-x","journal-title":"Thromb J"},{"key":"2726_CR32","doi-asserted-by":"publisher","first-page":"E2943","DOI":"10.3390\/jcm9092943","volume":"9","author":"M Vicenzi","year":"2020","unstructured":"Vicenzi M, Ruscica M, Iodice S, Rota I, Ratti A, Di Cosola R, Corsini A, Bollati V, Aliberti S, Blasi F (2020) The efficacy of the mineralcorticoid receptor antagonist canrenone in COVID-19 patients. J Clin Med 9:E2943. https:\/\/doi.org\/10.3390\/jcm9092943","journal-title":"J Clin Med"},{"key":"2726_CR33","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.3390\/v13112209","volume":"13","author":"N Kumar","year":"2021","unstructured":"Kumar N, Zuo Y, Yalavarthi S, Hunker KL, Knight JS, Kanthi Y, Obi AT, Ganesh SK (2021) SARS-CoV-2 Spike Protein S1-mediated endothelial injury and pro-inflammatory state is amplified by dihydrotestosterone and prevented by mineralocorticoid antagonism. Viruses 13:2209. https:\/\/doi.org\/10.3390\/v13112209","journal-title":"Viruses"},{"key":"2726_CR34","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1056\/NEJMoa030207","volume":"348","author":"B Pitt","year":"2003","unstructured":"Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M (2003) Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348:309\u20131321. https:\/\/doi.org\/10.1056\/NEJMoa030207","journal-title":"N Engl J Med"},{"key":"2726_CR35","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJM199909023411001","volume":"341","author":"B Pitt","year":"1999","unstructured":"Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341:709\u2013717. https:\/\/doi.org\/10.1056\/NEJM199909023411001","journal-title":"N Engl J Med"},{"key":"2726_CR36","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.kint.2018.08.024","volume":"95","author":"MJ Butler","year":"2019","unstructured":"Butler MJ, Ramnath R, Kadoya H, Desposito D, Riquier-Brison A, Ferguson JK, Onions KL, Ogier AS, ElHegni H, Coward RJ, Welsh GI, Foster RR, Peti-Peterdi J, Satchell SC (2019) Aldosterone induces albuminuria via matrix metalloproteinase-dependent damage of the endothelial glycocalyx. Kidney Int 95:94\u2013107. https:\/\/doi.org\/10.1016\/j.kint.2018.08.024","journal-title":"Kidney Int"}],"container-title":["Pfl\u00fcgers Archiv - European Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-022-02726-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00424-022-02726-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-022-02726-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T01:06:11Z","timestamp":1663808771000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00424-022-02726-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["2726"],"URL":"https:\/\/doi.org\/10.1007\/s00424-022-02726-3","relation":{},"ISSN":["0031-6768","1432-2013"],"issn-type":[{"value":"0031-6768","type":"print"},{"value":"1432-2013","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"assertion":[{"value":"10 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All sera of this study were collected according to the Declaration of Helsinki and after approval of the local ethics committee (patients with a mild course of COVID-19: Az 13-003; patients with severe course of COVID-19: Az 19-019\/A, control sera: Az 19-310, University of L\u00fcbeck). Primary human umbilical vein endothelial cells (HUVECs) were isolated from voluntary donated umbilical veins (approved by the local ethical committee (Az 18-325). All patients\/donors gave written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"See section above","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and animal ethics"}},{"value":"All patients gave their written informed consent to use patients sera for research projects.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}