Galectin-3 is Expressed in Vascular Smooth Muscle Cells and Promotes Pulmonary Hypertension through changes in Proliferation, Apoptosis and Fibrosis

A defining characteristic of Pulmonary Hypertension (PH) is the extensive remodeling of pulmonary arteries (PA) that results in progressive increases in vascular resistance and stiffness and eventual failure of the right ventricle. There is no cure for PH and identification of novel molecular mechanisms that underlie increased proliferation, reduced apoptosis and excessive extracellular matrix production in pulmonary artery smooth muscle cells (PASMC) is a vital objective. Galectin-3 (Gal-3) is a chimeric lectin and potent driver of many aspects of fibrosis, but its role in regulating PASMC behavior in PH remains poorly understood. Herein, we evaluated the importance of increased Gal-3 expression and signaling on PA vascular remodeling and cardiopulmonary function in experimental models of PH. Gal-3 expression was quantified by qRT-PCR, Western blotting and immunofluorescence imaging and its functional role was assessed by specific Gal-3 inhibitors and CRISPR-Cas9 mediated knockout of Gal-3 in the rat. In...