Document Detail


Mineralocorticoid Receptor Antagonists Modulate Galectin-3 and Interleukin-33/ST2 Signaling in Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction.
MedLine Citation:
PMID:  25458175     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: This study aimed to evaluate the specific role of the 2 available MRAs, eplerenone and spironolactone, on the modulation of galectin-3 (Gal-3) and interleukin (IL)-33/ST2 signaling in an experimental model of left ventricular systolic dysfunction after acute MI.
BACKGROUND: The molecular mechanisms of benefits of mineralocorticoid receptor antagonists (MRAs) in patients with left ventricular systolic dysfunction after myocardial infarction (MI) are not well understood.
METHODS: MI and left ventricular systolic dysfunction were induced by permanent ligation of the anterior coronary artery in 45 male Wistar rats, randomly assigned to no therapy (MI group, n = 15) or to receive MRAs (100 mg/kg/day) for 4 weeks; either eplerenone (n = 15) or spironolactone (n = 15) was used. A sham group was used as a control (n = 8). Elements of the pathway for Gal-3 including transforming growth factor (TGF)-β and SMAD3, as well as that for IL-33/ST2 (including IL-33 and soluble ST2 [sST2]) were analyzed in the infarcted and noninfarcted myocardium by quantitative real-time reverse transcription polymerase chain reaction. Expression of markers of fibrosis (collagen types I and III, tissue inhibitor of metalloproteinase-1) and inflammation (IL-6, tumor necrosis factor-α, monocyte chemotactic protein-1) was also examined.
RESULTS: In the infarcted myocardium, compared with sham animals, the MI group had higher concentrations of Gal-3, TGF-β, SMAD3, IL-33, and sST2, as well as higher concentrations of markers of fibrosis and inflammation. Treatment with MRAs down-regulated Gal-3, TGF-β, and SMAD3 and enhanced IL-33/ST2 signaling with lower expression of sST2; protective IL-33 up-regulation was unaffected by MRAs. Modulation of Gal-3 and IL-33/ST2 signaling induced by MRAs correlated with lower expression levels of fibrosis and inflammatory markers. No differences were found between eplerenone and spironolactone. In the noninfarcted myocardium, compared with sham animals, the MI group exhibited a higher expression of Gal-3 and IL-33, but no signs of inflammation or fibrosis were observed; in the presence of MRAs, IL-33 expression was significantly up-regulated, but Gal-3 was unaffected.
CONCLUSIONS: MRAs play a pivotal role in the Gal-3 and IL-33/ST2 modulation in post-MI cardiac remodeling.
Authors:
Antonio Lax; Jesus Sanchez-Mas; Maria C Asensio-Lopez; Maria J Fernandez-Del Palacio; Luis Caballero; Iris P Garrido; Francisco J Pastor-Perez; James L Januzzi; Domingo A Pascual-Figal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-12
Journal Detail:
Title:  JACC. Heart failure     Volume:  -     ISSN:  2213-1787     ISO Abbreviation:  JACC Heart Fail     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  101598241     Medline TA:  JACC Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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