Aortic stenosis (AS) is characterized by pressure overload and causes left ventricular (LV) fibrosis and inflammation, two mechanisms that eventually lead to cardiac dysfunction. Galectin-3 (Gal-3), a β-galactoside-binding lectin, promotes cardiac remodelling. In the present study, we investigated the role of Gal-3 in LV remodelling in patients with AS and the effects of Gal-3 blockade in rats subjected to short-term (6-week) supravalvular aortic banding (AS group). Myocardial biopsies were obtained from 25 patients with severe AS referred for aortic valve replacement and from necropsies of 11 cardiovascular disease-free control individuals. Gal-3 was up-regulated in myocardial biopsies from AS patients compared with controls. Gal-3 directly correlated with parameters assessing myocardial fibrosis and inflammation in AS patients. Normotensive AS animals presented decreased LV diastolic diameter compared with controls. At the histological level, AS rats exhibited a slight increase in LV cross-sectional area and LV wall thickness, and augmented cardiomyocyte width and cross-sectional area. AS animals presented enhanced cardiac Gal-3 expression, which paralleled higher myocardial fibrosis and inflammation. Cardiac Gal-3 was associated with fibrosis and inflammatory markers. Gal-3 pharmacological inhibition prevented the increase in cardiac Gal-3 and normalized histological and molecular alterations in AS rats. In short-term AS, the increase in myocardial Gal-3 expression was associated with cardiac fibrosis and inflammation, alterations that were prevented by Gal-3 blockade. These data suggest that Gal-3 inhibition could be a novel therapeutic approach in the prevention of AS-associated early pathological cardiac remodelling.
A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis
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Vanessa Arrieta, Ernesto Martinez-Martinez, Jaime Ibarrola, Virginia Alvarez, Rafael Sádaba, Amaia Garcia-Peña, Amaya Fernández-Celis, Victoria Cachofeiro, Patrick Rossignol, Natalia López-Andrés; A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis. Clin Sci (Lond) 1 May 2017; 131 (10): 935–949. doi: https://doi.org/10.1042/CS20170145
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