TY - JOUR
T1 - Galectin-3 mediates aldosterone-induced vascular fibrosis
AU - Calvier, Laurent
AU - Miana, Maria
AU - Reboul, Pascal
AU - Cachofeiro, Victoria
AU - Martinez-Martinez, Ernesto
AU - De Boer, Rudolf A.
AU - Poirier, Françoise
AU - Lacolley, Patrick
AU - Zannad, Faiez
AU - Rossignol, Patrick
AU - López-Andrés, Natalia
PY - 2013/1
Y1 - 2013/1
N2 - Objective-Aldosterone (Aldo) is involved in arterial stiffness and heart failure, but the mechanisms have remained unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, plays an important role in inflammation, fibrosis, and heart failure. We investigated here whether Gal-3 is involved in Aldo-induced vascular fibrosis. Methods and Results-In rat vascular smooth muscle cells Gal-3 overexpression enhanced specifically collagen type I synthesis. Moreover Gal-3 inhibition by modified citrus pectin or small interfering RNA blocked Aldo-induced collagen type I synthesis. Rats were treated with Aldo-salt combined with spironolactone or modified citrus pectin for 3 weeks. Hypertensive Aldo-treated rats presented vascular hypertrophy, inflammation, fibrosis, and increased aortic Gal-3 expression. Spironolactone or modified citrus pectin treatment reversed all the above effects. Wild-type and Gal-3 knock-out mice were treated with Aldo for 6 hours or 3 weeks. Aldo increased aortic Gal-3 expression, inflammation, and collagen type I in wild-type mice at both the short-and the long-term, whereas no changes occurred in Gal-3 knock-out mice. Conclusion-Our data indicate that Gal-3 is required for inflammatory and fibrotic responses to Aldo in vascular smooth muscle cells in vitro and in vivo, suggesting a key role for Gal-3 in vascular fibrosis.
AB - Objective-Aldosterone (Aldo) is involved in arterial stiffness and heart failure, but the mechanisms have remained unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, plays an important role in inflammation, fibrosis, and heart failure. We investigated here whether Gal-3 is involved in Aldo-induced vascular fibrosis. Methods and Results-In rat vascular smooth muscle cells Gal-3 overexpression enhanced specifically collagen type I synthesis. Moreover Gal-3 inhibition by modified citrus pectin or small interfering RNA blocked Aldo-induced collagen type I synthesis. Rats were treated with Aldo-salt combined with spironolactone or modified citrus pectin for 3 weeks. Hypertensive Aldo-treated rats presented vascular hypertrophy, inflammation, fibrosis, and increased aortic Gal-3 expression. Spironolactone or modified citrus pectin treatment reversed all the above effects. Wild-type and Gal-3 knock-out mice were treated with Aldo for 6 hours or 3 weeks. Aldo increased aortic Gal-3 expression, inflammation, and collagen type I in wild-type mice at both the short-and the long-term, whereas no changes occurred in Gal-3 knock-out mice. Conclusion-Our data indicate that Gal-3 is required for inflammatory and fibrotic responses to Aldo in vascular smooth muscle cells in vitro and in vivo, suggesting a key role for Gal-3 in vascular fibrosis.
KW - aldosterone
KW - collagen type I
KW - fibrosis
KW - galectin-3
KW - vascular smooth muscle cells
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U2 - 10.1161/ATVBAHA.112.300569
DO - 10.1161/ATVBAHA.112.300569
M3 - Article
C2 - 23117656
AN - SCOPUS:84871813952
SN - 1079-5642
VL - 33
SP - 67
EP - 75
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 1
ER -