[Balectin-3 affects the stability of vulnerable coronary atherosclerosis plaques by targeted modulation of lncARSR].

OBJECTIVE

To investigate the mechanism by which galectin-3 (Gal-3) affects the stability of vulnerable coronary atherosclerosis plaques through long non-coding RNA ARSR (lncARSR).

METHOD

Male BALB/c mice were randomly divided into normal diet group, high-fat diet group, high-fat diet+lncARSR inhibitor group (=20). The high-fat diet contained 15% fat and 0.25% cholesterol, and lncARSR inhibitor was injected intravenously at 50 nmol/L every other day. After 12 weeks of high-fat diet feeding and treatment, the mice were euthanized for analyzing coronary atherosclerosis and plaque damage using Sudan IV and oil red O staining. The protein expressions of Gal-3 and ARSR in the coronary artery of the mice were analyzed with Western blotting, and the expressions of PI3K and Akt were detected with immunohistochemistry. The coronary artery tissues were harvested from normal mice for cell culture, and the isolated cells were transfected with a Gal-3 mimic or a Gal-3 inhibitor. At 24 h after the transfection, dual luciferase reporter gene assay was performed to determine the target relationship between Gal-3 and lncARSR; the mRNA expressions of tumor necrosis factor (TNF-), interleukin-β (IL-β) and IL-6 in the transfected cells were detected with RT-qPCR.

RESULTS

The positively stained areas by Sudan IV and red oil O and the protein expression of lncARSR were the lowest in normal diet group and the highest in high-fat diet group ( < 0.05). The protein expression of PI3K and Akt and the mRNA expression of TNF-, IL-β and IL-6 in high-fat diet group were higher than those in normal diet group. The protein expression of PI3K and Akt and the mRNA expression of TNF-, IL-β and IL-6 in high-fat diet+ lncARSR inhibitor group were significantly lower than those in high-fat diet group ( < 0.05). In the cell experiment, the activity of WT-lncARSR was significantly higher in Gal-3 mimic transfection group than in the control group and Gal-3 inhibition group (=0.026), and was the lower in Gal-3 inhibition group than in the control group (=0.017).

CONCLUSION

Gal-3 and lncARSR are overexpressed in coronary atherosclerosis. Through a mechanism for targeted inhibition of lncARSR, Gal-3 regulates the PI3K/ Akt signaling pathway to suppress inflammation and thus regulate the stability of vulnerable coronary atherosclerosis plaques.