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Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in Experimental Hyperaldosteronism and HypertensionNovelty and Significance

Abstract : 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.
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https://hal.univ-lorraine.fr/hal-01745541
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Submitted on : Wednesday, March 28, 2018 - 12:24:17 PM
Last modification on : Saturday, December 5, 2020 - 2:08:02 PM

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Ernesto Martinez-Martinez, Laurent Calvier, Amaya Fernández-Celis, Elodie Rousseau, Raquel Jurado-López, et al.. Galectin-3 Blockade Inhibits Cardiac Inflammation and Fibrosis in Experimental Hyperaldosteronism and HypertensionNovelty and Significance. Hypertension, American Heart Association, 2015, 66 (4), pp.767 - 775. ⟨10.1161/HYPERTENSIONAHA.115.05876⟩. ⟨hal-01745541⟩

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