Aldosterone induced galectin-3 secretion in vitro and in vivo: from cells to humans

PLoS One. 2014 Sep 2;9(9):e95254. doi: 10.1371/journal.pone.0095254. eCollection 2014.

Abstract

Context: Patients with primary aldosteronism are associated with increased myocardial fibrosis. Galectin-3 is one of the most important mediators between macrophage activation and myocardial fibrosis.

Objective: To investigate whether aldosterone induces galectin-3 secretion in vitro and in vivo.

Methods and results: We investigated the possible molecular mechanism of aldosterone-induced galectin-3 secretion in macrophage cell lines (THP-1 and RAW 264.7 cells). Aldosterone induced galectin-3 secretion through mineralocorticoid receptors via the PI3K/Akt and NF-κB transcription signaling pathways. In addition, aldosterone-induced galectin-3 expression enhanced fibrosis-related factor expression in fibroblasts. We observed that galectin-3 mRNA from peripheral blood mononuclear cells and serum galectin-3 levels were both significantly increased in mice implanted with aldosterone pellets on days 7 and 14. We then conducted a prospective preliminary clinical study to investigate the association between aldosterone and galectin-3. Patients with aldosterone-producing adenoma had a significantly higher plasma galectin-3 level than patients with essential hypertension. One year after adrenalectomy, the plasma galectin-3 level had decreased significantly in the patients with aldosterone-producing adenoma.

Conclusion: This study demonstrated that aldosterone could induce galectin-3 secretion in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy
  • Aldosterone / pharmacology*
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibrosis
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Hyperaldosteronism / genetics
  • Hyperaldosteronism / metabolism
  • Hyperaldosteronism / pathology
  • Hyperaldosteronism / surgery
  • Male
  • Mice
  • Myocardium / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Galectin 3
  • RNA, Messenger
  • Aldosterone

Grants and funding

This study was supported by grants from the National Taiwan University Hospital (NTUH 101-001974), National Taiwan University (National Taiwan University Cutting-Edge Steering Research 10R71608-1), NTU-NTUH MediaTek Innovative Medical Electronics Research Center (PC851), Taiwan National Science Council (NSC 100-2314-B-002-139, NSC 102-2314-B-002-078-MY3), and Taiwan National Science Council support for the Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan (NSC 101-2911-I-008-001). The funders had no role in study design, data collection or analysis, decision to publish, or preparation of the manuscript.