TY - JOUR
T1 - Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension
AU - Martínez-Martínez, Ernesto
AU - Calvier, Laurent
AU - Fernández-Celis, Amaya
AU - Rousseau, Elodie
AU - Jurado-López, Raquel
AU - Rossoni, Luciana V.
AU - Jaisser, Frederic
AU - Zannad, Faiez
AU - Rossignol, Patrick
AU - Cachofeiro, Victoria
AU - López-Andrés, Natalia
N1 - Publisher Copyright:
© 2015 American Heart Association, Inc.
PY - 2015/10/11
Y1 - 2015/10/11
N2 - Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.
AB - Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension.
KW - aldosterone
KW - fibrosis
KW - galectin 3
KW - hypertension
KW - inflammation
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U2 - 10.1161/HYPERTENSIONAHA.115.05876
DO - 10.1161/HYPERTENSIONAHA.115.05876
M3 - Article
C2 - 26238446
AN - SCOPUS:84941217103
SN - 0194-911X
VL - 66
SP - 767
EP - 775
JO - Hypertension
JF - Hypertension
IS - 4
ER -