Galectin-3 induces vascular smooth muscle cells calcification via AMPK/TXNIP pathway.

Galectin-3 plays an important role in atherosclerosis. Upregulation of VSMCs calcification is involved in the progression and development of vulnerable plaques. Thioredoxin-interacting protein (TXNIP) has been regarded as an important determinant in regulating inflammation and oxidative stress. In this study, we evaluated the role of TXNIP in galectin-3-induced vascular calcification. A primary culture of mouse VSMCs was established by enzymatic digestion of aorta. Small interfering (si) RNA was used to knock down the expression of target gene. VSMCs were treated with 3-methyladenine (3-MA) or compound C respectively. Western blot was performed to detect the protein level in VSMCs, Alkaline phosphatase (ALP) and Alizarin red staining was used to observe calcium deposition. Dihydroethidium (DHE) staining was used to observe the reactive oxygen species (ROS) production. Here we showed that galectin-3 increased aorta and VSMCs calcification, which was associated with AMPK/TXNIP upregulation and autophagy activation. TXNIP inhibition decreased galectin-3-induced aorta and VSMCs calcification and autophagy activation. 3-MA or Atg5 siRNA decreased galectin-3-induced upregulation of Runx2, BMP2 and OPN. AMPK mediated galectin-3-induced VSMCs osteogenic differentiation. These findings illustrated that TXNIP mediated galectin-3-induced vascular calcification, AMPK and autophagy activation were also associated with this process.