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

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.

Antitumor effects of galectin-3 inhibition in human renal carcinoma cells

“…Gal-3 was abnormally regulated in pathological conditions, such as inflammation and cardiovascular diseases. 4,5 Moreover, expression and subcellular distribution of Gal-3 change with cellular differentiation, development, as well as carcinogenesis. 6 Interestingly, Gal-3 expression was reported to increase in RCC tissue and was supposed to associate with prevalence of RCC.…”

Intranuclear accumulation of galectin-3 is associated with a poor prognosis in patients with invasive intraductal papillary mucinous neoplasm

“…There were a few reports concerning the relationship between galectin3 expression in the pancreas and pancreatitis 35,36) . Recently, there has been focus on galectin-3 because of its roles in fibrosis in various diseases 34,[37][38] , although the precise mechanism has not yet been elucidated 39) . The incidence of dilatation of the main pancreatic ducts was higher in the high galectin-3 expression group.…”

Vascular Mineralocorticoid Receptors

“…Galectin-3-deficient mice were protected from aldosterone-induced cardiac remodeling. 42 In conclusion, inflammation is a key mechanism mediating the detrimental effects of aldosterone in the cardiovascular system. MR in endothelial cells determines leukocyte adhesion and transmigration throughout diverse experimental models of cardiovascular injury.…”

“…40 In experimental models, galectin-3 is upregulated by high-fat diet, 40 isoproteronol, 41 or aldosterone treatment. 42 Treatment with the galectin-3 inhibitor-modified citrus pectin 40,41 or spironolactone 41,42 similarly prevented cardiac and aortic inflammation and fibrosis. Galectin-3-deficient mice were protected from aldosterone-induced cardiac remodeling.…”