Background. Aldosterone (Aldo) plays a major role in extracellular matrix (ECM) remodeling leading to heart failure (HF), but the mechanisms remained unclear. Galectin-3 (Gal-3), a β-galactosidase-binding lectin, plays an important role in inflammation and HF. We 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) antagonist. Gal-3 was over-expressed (transfection) and knocked-down (siRNA). Gal-3 expression and ECM production were evaluated by RT-PCR, Western blot and immunohistochemistry. In vivo, Wistar rats were treated by Aldo (1mg/kg/day)+salt or Aldo+salt+spironolactone (200mg/kg/day) for 3 weeks. Gal-3 and ECM proteins (collagen type I and III, fibronectin and elastin) were quantified by Western Blot and immunohistochemistry, and metalloproteinase (MMP) activities by zymography.

Results. In vitro, VSMCs spontaneously expressed Gal-3. Gal-3 over-expression enhanced ECM synthesis. Aldo up-regulated Gal-3 and ECM protein expression via MR. The Gal-3 silencing blocked Aldo-induced ECM production by VSMCs. In Aldo-salt hypertensive rats, Gal-3 aortic expression, ECM proteins and MMP activities were enhanced. Spironolactone treatment reversed all the above effects. Aortic Gal-3 expression was positively correlated with collagen type I, elastin, MMP-2 and MMP-13 activity.

Conclusions. Gal-3 is spontaneously expressed by VSMCs and induces ECM synthesis. It mediates Aldo-induced ECM remodeling via MR activation in vitro and in vivo. Our data suggest a key role for Gal-3 in Aldo-induced vascular alterations.