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Essential role of ICAM-1 in aldosterone-induced atherosclerosis.

Marzolla, V; Armani, A; Mammi, C; Moss, ME; Pagliarini, V; Pontecorvo, L; Antelmi, A; Fabbri, A; Rosano, G; Jaffe, IZ; et al. Marzolla, V; Armani, A; Mammi, C; Moss, ME; Pagliarini, V; Pontecorvo, L; Antelmi, A; Fabbri, A; Rosano, G; Jaffe, IZ; Caprio, M (2017) Essential role of ICAM-1 in aldosterone-induced atherosclerosis. Int J Cardiol, 232. pp. 233-242. ISSN 1874-1754 https://doi.org/10.1016/j.ijcard.2017.01.013
SGUL Authors: Rosano, Giuseppe Massimo Claudio

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Abstract

OBJECTIVE: Elevated aldosterone is associated with increased risk of atherosclerosis complications, whereas treatment with mineralocorticoid receptor (MR) antagonists decreases the rate of cardiovascular events. Here we test the hypothesis that aldosterone promotes early atherosclerosis by modulating intercellular adhesion molecule-1 (ICAM-1) expression and investigate the molecular mechanisms by which aldosterone regulates ICAM-1 expression. METHODS AND RESULTS: Apolipoprotein-E (ApoE)-/- mice fed an atherogenic diet and treated with aldosterone for 4weeks showed increased vascular expression of ICAM-1, paralleled by enhanced atherosclerotic plaque size in the aortic root. Moreover, aldosterone treatment resulted in increased plaque lipid and inflammatory cell content, consistent with an unstable plaque phenotype. ApoE/ICAM-1 double knockout (ApoE-/-/ICAM-1-/-) littermates were protected from the aldosterone-induced increase in plaque size, lipid content and macrophage infiltration. Since aldosterone is known to regulate ICAM-1 transcription via MR in human endothelial cells, we explored MR regulation of the ICAM-1 promoter. Luciferase reporter assays performed in HUVECs using deletion constructs of the human ICAM-1 gene promoter showed that a region containing a predicted MR-responsive element (MRE) is required for MR-dependent transcriptional regulation of ICAM-1. CONCLUSIONS: Pro-atherogenic effects of aldosterone are mediated by increased ICAM-1 expression, through transcriptional regulation by endothelial MR. These data enhance our understanding of the molecular mechanism by which MR activation promotes atherosclerosis complications.

Item Type: Article
Additional Information: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Aldosterone, Atherosclerosis, Endothelial cells, Intercellular adhesion molecule-1, Mineralocorticoid receptor, Aldosterone, Animals, Atherosclerosis, Blotting, Western, Cells, Cultured, Disease Models, Animal, Endothelium, Vascular, Flow Cytometry, Gene Expression Regulation, Genotype, Immunohistochemistry, Intercellular Adhesion Molecule-1, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Receptors, Mineralocorticoid, Endothelium, Vascular, Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Disease Models, Animal, Aldosterone, Intercellular Adhesion Molecule-1, Receptors, Mineralocorticoid, RNA, Blotting, Western, Flow Cytometry, Immunohistochemistry, Gene Expression Regulation, Genotype, Male, Atherosclerosis, 1102 Cardiovascular Medicine And Haematology, Cardiovascular System & Hematology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Int J Cardiol
ISSN: 1874-1754
Language: eng
Dates:
DateEvent
1 April 2017Published
5 January 2017Published Online
3 January 2017Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
R01 HL095590National Institutes of Healthhttp://dx.doi.org/10.13039/100000002
GR-2009-1594563Italian Ministry of HealthUNSPECIFIED
PE-2011-02347070Italian Ministry of HealthUNSPECIFIED
PubMed ID: 28089144
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111198
Publisher's version: https://doi.org/10.1016/j.ijcard.2017.01.013

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