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.

Galectin‐3 and risk of cardiovascular events and all‐cause mortality in type 2 diabetes

“…Galectin‐3 has recently emerged as a potential novel biotarget in heart failure and renal fibrosis, and galectin‐3 has also been implicated in atherosclerosis . Persons with type 2 diabetes with or without cardiovascular disease are known to have higher galectin‐3 levels .…”

“…Expression of galectin‐3 was particularly up‐regulated in unstable regions of human atherosclerotic plaques, and the local increase in galectin‐3 concentration exacerbated the pro‐inflammatory state in atherosclerotic lesions by enhancing the recruitment of monocytes and macrophages to the artery wall . Galectin‐3 could also promote the activation of vascular smooth muscle cells induced by oxidized LDL in atherosclerotic plaques . Furthermore, galectin‐3 may be proatherogenic by inducing insulin resistance .…”

“…Galectin-3 has recently emerged as a potential novel biotarget in heart failure and renal fibrosis, and galectin-3 has also been implicated in atherosclerosis. [9][10][11][12] Persons with type 2 diabetes with or without cardiovascular disease are known to have higher galectin-3 levels. [22][23][24][25] In a cross-sectional study, Ozturk et al reported that serum galectin-3 levels correlated with the total number of diseased vessels and the number and type of plaques in type 2 diabetic individuals with coronary artery disease.…”

“…The role of galectin‐3 in atherosclerosis is more controversial. Some but all experimental studies have suggested that galectin‐3 may be involved in the pathogenesis of atherosclerosis, and inhibition of galectin‐3 can reduce atherosclerotic lesions and slow atherosclerotic plaque progression in mouse models . In high risk patients with coronary heart disease, galectin‐3 level has been shown to predict cardiovascular death and prognosis after myocardial infarction .…”

Galectin-3 in acute coronary syndrome

“…Finally, a pivotal process that contributes to plaque instability and progression of the atherosclerotic lesions is the phenotypic change of vascular smooth muscle cells (VSMCs) from a differentiated state to a dedifferentiated state. In vitro experiments have shown Gal-3 is involved in the phenotypic transformation of VSMCs [30].…”