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Aldosterone Rapidly Induces Leukocyte Adhesion to Endothelial Cells: A New Link Between Aldosterone and Arteriosclerosis?

2007; Lippincott Williams & Wilkins; Volume: 50; Issue: 5 Linguagem: Inglês

10.1161/hypertensionaha.107.099531

1524-4563

Alexander W. Krug, Steffi Kopprasch, Christian G. Ziegler, Sandra Dippong, Rusan Catar, Stefan R. Bornstein, Henning Morawietz, Michael Gekle,

Apelin-related biomedical research

HomeHypertensionVol. 50, No. 5Aldosterone Rapidly Induces Leukocyte Adhesion to Endothelial Cells: A New Link Between Aldosterone and Arteriosclerosis? Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAldosterone Rapidly Induces Leukocyte Adhesion to Endothelial Cells: A New Link Between Aldosterone and Arteriosclerosis? Alexander W. Krug, Steffi Kopprasch, Christian G. Ziegler, Sandra Dippong, Rusan A. Catar, Stefan R. Bornstein and Henning Morawietz Michael Gekle Alexander W. KrugAlexander W. Krug Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Dresden, Germany , Steffi KoppraschSteffi Kopprasch Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Dresden, Germany , Christian G. ZieglerChristian G. Ziegler Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Dresden, Germany , Sandra DippongSandra Dippong Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Dresden, Germany , Rusan A. CatarRusan A. Catar Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Dresden, Germany , Stefan R. BornsteinStefan R. Bornstein Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Dresden, Germany and Henning MorawietzHenning Morawietz Carl Gustav Carus University Hospital, Medical Clinic III, University of Dresden, Dresden, Germany Michael GekleMichael Gekle Julius-Bernstein-Institut für Physiologie, University Halle-Wittenberg, Halle, Germany Originally published24 Sep 2007https://doi.org/10.1161/HYPERTENSIONAHA.107.099531Hypertension. 2007;50:e156–e157Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 24, 2007: Previous Version 1 To the Editor:Aldosterone is known to induce cardiovascular dysfunction, including fibrosis, inflammation, and endothelial dysfunction, as well as thrombosis formation.1 Clinical trials have shown aldosterone to be an independent predictor of increased mortality in patients with chronic heart failure,2 and high circulating plasma aldosterone levels predict the clinical outcome in patients after myocardial infarction.3 Mineralocorticoid receptor blockade proved to exert beneficial effects in clinical trials, such as the Randomised Aldactone Evaluation Study and the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study.4 Recent studies provided evidence for a role of aldosterone in the pathogenesis of arteriosclerosis.5 However, the exact mechanisms of adverse aldosterone actions in the cardiovascular system are largely unknown. Here, we aimed at elucidating rapid (60 minutes) aldosterone effects on interactions between endothelial cells and leukocytes.We performed adhesion experiments using primary cultures of freshly isolated human endothelial cells from the umbilical cord vein (HUVECs) and polymorphonuclear leukocytes (PMNs).6 Adhesion of leukocytes is mediated by adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and e-selectin.7 Therefore, we assessed expression of these molecules by Western blot analysis and immunohistochemistry8 in isolated HUVECs and human umbilical artery endothelial cells.Figure 1A shows stimulated adhesion of PMNs to a monolayer of HUVECs after incubation of endothelial cells with increasing aldosterone concentrations (1 to 100 nmol/L). The effect observed was concentration dependent, indicating specificity for aldosterone. Leukocyte adhesion reaches a maximum after 1 hour with no further increase (Figure 1B). Figure 1C shows representative light microscopic images of adhering leukocytes after treatment of HUVECs with 10 nmol/L of aldosterone for 60 minutes. Figure 2 shows that expression of adhesion molecules is upregulated after a 1-hour treatment of HUVECs (Figure 2A and 2B) and human umbilical artery endothelial cells (Figure 2C and 2D) with 10 nmol/L of aldosterone. Download figureDownload PowerPointFigure 1. A, Dose response (1 to 100 nmol/L) of aldosterone-induced adhesion of PMNs to HUVECs; low-density lipoproteins (LDLs) served as positive controls. B, Time course (0 to 180 minutes) of aldosterone-induced adhesion of PMNs to HUVECs after incubation of the cells with 10 nmol/L of aldosterone. n=4 to 8 from ≥3 different cell preparations. C, Light-microscopic pictures show enhanced adhesion of PMNs to HUVECs after incubation of the cells with 10 nmol/L aldosterone for 60 minutes; mean±SEM, significance of difference was tested by ANOVA; *P<0.05.Download figureDownload PowerPointFigure 2. Regulation of adhesion molecule expression by aldosterone in HUVECs (A and B) and human umbilical artery endothelial cells (C and D). Increased protein expression of vascular cell adhesion molecule (VCAM)-1, e-selectin, and intercellular adhesion molecule-1 (ICAM-1) as demonstrated by Western blot (A and C) and immunofluorescence (B and D) after 60-minute incubation of cells with 10 nmol/L of aldosterone. Each blot is a representative blot from 3 to 5 different experiments from 2 to 5 different cell preparations. Blue indicates nuclear staining and green indicates fluoresceinisothiocyanate secondary antibody staining of VCAM-1.Exposure of HUVECs to aldosterone (10 to 100 nmol/L) induces adhesion of PMNs to the endothelial cells within 60 minutes, suggesting absence of de novo mineralocorticoid receptor–mediated protein synthesis. Aldosterone is known to exert rapid effects by interfering with peptide signaling cascades, such as extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases,9 and evidence suggests that rapid aldosterone effects might play a role in cardiac dysfunction.10 Mitogen-activated protein kinase activation plays an essential role in aldosterone-mediated cardiovascular damage, and mitogen-activated protein kinase activation is known to occur within minutes after aldosterone exposure to endothelial cells.11 Our data demonstrate a cellular mechanism of aldosterone-mediated endothelial dysfunction and support the idea of a rapid signaling mechanism as being responsible for the aldosterone-mediated upregulation of adhesion molecules.Nonhemodynamic cardiovascular effects of aldosterone result in fibrosis and inflammation. Future studies will have to address the possible receptor that mediates rapid aldosterone effects and also will have to critically evaluate their pathophysiological importance in vivo.Sources of FundingThis work was funded by grants to A.W.K. (MedDrive, University of Dresden and Dr Robert Pfleger Stiftung).DisclosuresNone.1 Schiffrin EL. Effects of aldosterone on the vasculature. Hypertension. 2006; 47: 312–318.LinkGoogle Scholar2 Güder G, Bauersachs J, Frantz S, Weismann D, Allolio B, Ertl G, Angermann CE, Störk S. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation. 2007; 115: 1754–1761.LinkGoogle Scholar3 Beygui F, Collet JP, Benoliel JJ, Vignolles N, Dumaine R, Barthélémy O, Montalescot G. High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation. 2006; 114: 2604–2610.LinkGoogle Scholar4 Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. 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. 2003; 348: 1309–1321.CrossrefMedlineGoogle Scholar5 Takai S, Jin D, Muramatsu M, Kirimura K, Sakonjo H, Miyazaki M. Eplerenone inhibits atherosclerosis in nonhuman primates. Hypertension. 2005; 46: 1135–1139.LinkGoogle Scholar6 Kopprasch S, Richter K, Leonhardt W, Pietzsch J, Grässler J. Urate attenuates oxidation of native low-density lipoprotein by hypochlorite and the subsequent lipoprotein-induced respiratory burst activities of polymorphonuclear leukocytes. Mol Cell Biochem. 2000; 206: 51–56.CrossrefMedlineGoogle Scholar7 Morawietz H, Rueckschloss U, Niemann B, Duerrschmidt N, Galle J, Hakim K, Zerkowski HR, Sawamura T, Holtz J. Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein. Circulation. 1999; 100: 899–902.CrossrefMedlineGoogle Scholar8 Krug AW, Vleugels K, Schinner S, Lamounier-Zepter V, Ziegler CG, Bornstein SR, Ehrhart-Bornstein M. Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of steroidogenic acute regulatory protein (StAR) and an angiotensin II-sensitization in human adrenocortical cells. Int J Obes (Lond). Epub 24 April, 2007; doi:10.1038/sj.ijo.0803642.Google Scholar9 Krug AW, Schuster C, Gassner B, Freudinger R, Mildenberger S, Troppmair J, Gekle M. Human epidermal growth factor receptor-1 expression renders Chinese hamster ovary cells sensitive to alternative aldosterone signaling. J Biol Chem. 2002; 277: 45892–45897.CrossrefMedlineGoogle Scholar10 Chai W, Garrelds IM, de Vries R, Batenburg WW, van Kats JP, Danser AH. Nongenomic effects of aldosterone in the human heart: interaction with angiotensin II. Hypertension. 2005; 46: 701–706.LinkGoogle Scholar11 Grossmann C, Benesic A, Krug AW, Freudinger R, Mildenberger S, Gassner B, Gekle M. Human mineralocorticoid receptor expression renders cells responsive for nongenotropic aldosterone actions. Mol Endocrinol. 2005; 19: 1697–1710.CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Abdellatif A, Fernandes-Rosa F, Boulkroun S and Zennaro M (2022) Vascular and hormonal interactions in the adrenal gland, Frontiers in Endocrinology, 10.3389/fendo.2022.995228, 13 Kalkman H (2020) The Association Between Vascular Inflammation and Depressive Disorder. Causality, Biomarkers and Targeted Treatment, Pharmaceuticals, 10.3390/ph13050092, 13:5, (92) Milla S, Massart S, Mathieu C, Wang N, Douny C, Douxfils J, Scippo M, De Pauw E, Dieu M, Silvestre F and Kestemont P (2018) Physiological and proteomic responses to corticosteroid treatments in Eurasian perch, Perca fluviatilis : Investigation of immune-related parameters, Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 10.1016/j.cbd.2017.11.005, 25, (86-98), Online publication date: 1-Mar-2018. (2014) Spironolactone for Heart Failure with Preserved Ejection Fraction, New England Journal of Medicine, 10.1056/NEJMc1405715, 371:2, (179-182), Online publication date: 10-Jul-2014. Ye L, Guo J and Ge R (2014) Environmental Pollutants and Hydroxysteroid Dehydrogenases Endocrine Disrupters, 10.1016/B978-0-12-800095-3.00013-4, (349-390), . 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Deuchar G, McLean D, Hadoke P, Brownstein D, Webb D, Mullins J, Chapman K, Seckl J and Kotelevtsev Y (2011) 11β-Hydroxysteroid Dehydrogenase Type 2 Deficiency Accelerates Atherogenesis and Causes Proinflammatory Changes in the Endothelium in Apoe−/− Mice, Endocrinology, 10.1210/en.2010-0925, 152:1, (236-246), Online publication date: 1-Jan-2011. Taneja S and Mandal R (2010) Antihypertensive effect of Cu and Mg enriched modified poultry eggΨ on Zn-induced hypertension in Wistar rat, Journal of Trace Elements in Medicine and Biology, 10.1016/j.jtemb.2010.01.001, 24:3, (185-192), Online publication date: 1-Jul-2010. Muller G and Morawietz H (2009) Nitric Oxide, NAD(P)H Oxidase, and Atherosclerosis, Antioxidants & Redox Signaling, 10.1089/ars.2008.2403, 11:7, (1711-1731), Online publication date: 1-Jul-2009. Kopprasch S, Pietzsch J, Ansurudeen I, Graessler J, Krug A, Ehrhart-Bornstein M and Bornstein S Prediabetic and diabetic in vivo modification of circulating low-density lipoprotein attenuates its stimulatory effect on adrenal aldosterone and cortisol secretion, Journal of Endocrinology, 10.1677/JOE-08-0293, 200:1, (45-52) November 2007Vol 50, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.107.099531PMID: 17893423 Originally publishedSeptember 24, 2007 PDF download Advertisement SubjectsMechanisms