Essential role of ICAM-1 in aldosterone-induced atherosclerosis

Vittoria Pagliarini, Vincenzo Marzolla, Andrea Armani, Caterina Mammi, Mary E. Moss, Laura Pontecorvo, Antonella Antelmi, Andrea Fabbri, Giuseppe Rosano, Iris Z. Jaffe, Massimiliano Caprio

Risultato della ricerca: Contributo in rivistaArticolo in rivista

48 Citazioni (Scopus)

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 4 weeks 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.
Lingua originaleEnglish
pagine (da-a)233-242
Numero di pagine10
RivistaINTERNATIONAL JOURNAL OF CARDIOLOGY
Volume232
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Aldosterone
  • Animals
  • Atherosclerosis
  • Blotting, Western
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial cells
  • Endothelium, Vascular
  • Flow Cytometry
  • Gene Expression Regulation
  • Genotype
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1
  • Intercellular adhesion molecule-1
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mineralocorticoid receptor
  • RNA
  • Receptors, Mineralocorticoid

Fingerprint

Entra nei temi di ricerca di 'Essential role of ICAM-1 in aldosterone-induced atherosclerosis'. Insieme formano una fingerprint unica.

Cita questo