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

Abstract

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.