P152Galectin-3 is a potential mediator of aldosterone effects in vascular remodeling

    loading  Checking for direct PDF access through Ovid

Abstract

Background

Aldosterone (Aldo) is involved in extracellular matrix (ECM) remodeling and inflammation leading to heart failure (HF), but its mechanisms remains unknown. Galectin-3 (Gal-3), a β-galactosidase-binding lectin, plays an important role in inflammation and HF. We have investigated whether Gal-3 mediates Aldo-induced ECM remodeling in vascular smooth muscle cells (VSMCs) in vitro and in vivo.

Methods

In vitro, primary cultured VSMCs were stimulated with Aldo (10-8M) for 24h, with or without mineralocorticoid receptor (MR) antagonists (eplerenone, RU28318) and Gal-3 inhibitors (modified citrus pectin, N-acetyllactosamine, lactose). Gal-3 was over-expressed (transfection) and knocked-down (siRNA). In vivo, Wistar rats were treated with Aldo (1mg/kg/day) + salt or Aldo + salt + spironolactone (200mg/kg/day) for 3 weeks. Gal-3 expression, ECM production (collagen type I and III, fibronectin and elastin) and degradation (MMP activities) were evaluated by RT-PCR, Western blot, zymography and immunohistochemistry in VSMCs and aorta.

Results

Gal-3 was spontaneously expressed in cultured VSMCs. Its over-expression enhanced collagen type I production. Aldo up-regulated Gal-3 levels in a dose- and time-dependent manner via the mineralocorticoid receptor. Gal-3 chemical inhibitors blocked Aldo-induced ECM protein production. In addition, Gal-3 silencing abolished Aldo-induced collagen type I synthesis. In Aldo-salt hypertensive rats, aortic Gal-3 expression, ECM proteins and MMP activities were enhanced. Spironolactone treatment reversed all the above effects. Aortic Gal-3 expression was positively correlated with vascular collagen type I, elastin, MMP-2 and MMP-13 activities.

Conclusions

Aldo up-regulates Gal-3 expression via its mineralocorticoid receptor in VSMCs in vitro and in vivo. Gal-3 over-expression induces collagen type I synthesis. Moreover, Gal-3 is required for the fibrotic response to Aldo. Our data suggest a key role for Gal-3 in Aldo-induced vascular collagen accumulation.

Related Topics

    loading  Loading Related Articles