Galectin-3-induced oxidized low-density lipoprotein promotes the phenotypic transformation of vascular smooth muscle cells

Oxidized low-density lipoprotein (oxLDL) is involved in the pathological phenotypic transformation of vascular smooth muscle cells in atherosclerosis. Galectin-3 also has an important role in atherosclerosis. However, little is currently known regarding the effects of galectin-3 on the oxLDL-induced phenotypic transformation of vascular smooth muscle cells. In the present study, primary culture human umbilical vascular smooth muscle cells were treated with various oxLDL concentrations (0-50 μg/ml) for 72 h, and phenotypic changes were subsequently recorded. The results of the present study suggested that oxLDL increases the expression levels of galectin-3, and induces the phenotypic transformation of vascular smooth muscle cells. The oxLDL-induced cells exhibited increased expression levels of osteopontin, a smooth muscle synthetic protein, and calponin and α-actin, smooth muscle contractile proteins. The oxLDL-induced changes in cellular phenotype were associated with increased migration, proliferation, and phagocytosis. Concordant with these results, oxLDL-treated smooth muscle cells exhibited activation of canonical Wnt signaling, as determined by an increase in the protein expression levels of β-catenin. Silencing of galectin-3 by small interfering RNA reversed the phenotypic transformation and functional changes observed in the oxLDL-treated cells, suggesting these changes were dependent on the activation of galectin-3. In addition, galectin-3 knockdown decreased the protein expression levels of β-catenin in both the cytoplasm and nucleus; however, the mRNA expression levels of β-catenin remained unchanged. These results suggest that galectin-3 is responsible for the phenotypic transformation of human umbilical vascular smooth muscle cells, and the canonical Wnt/β-catenin signaling pathway may be involved in this process.