SGLT2 inhibitors attenuate cholesterol accumulation in Human Aortic Smooth Muscle Cells

The influence of SGLT2 inhibitors (SGLT2i) on cholesterol accumulation in Human Aortic Smooth Muscle Cells (HAoSMCs) has not yet been evaluated. This study aimed to assess the effect of SGLT2 inhibitors on cholesterol accumulation in HAoSMCs.

HAoSMCs were treated with empagliflozin (1 and 10 ​μM), dapagliflozin (1 and 10 ​μM), and canagliflozin (1 and 10 ​μM), with or without cholesterol-methyl-β-cyclodextrin complex (cholesterol complex), for 144 ​h. Lipid accumulation was assessed using Oil Red O staining, and absorbance at 492 ​nm was measured to quantify lipid content. Relative absorbance values were calculated against a medium control.

Incubation of HAoSMCs with 10 ​μg/ml cholesterol complex resulted in a significant increase (31.8 ​%) in absorbance compared to untreated cells (p ​< ​0.0001). The presence of SGLT2 inhibitors significantly reduced the absorbance to 9.8-18.2 ​% in comparison to 31.8 ​% cholesterol complex alone. This effect was statistically significant for empagliflozin at 1 ​μM and 10 ​μM (p ​= ​0.0497 and p ​= ​0.0026, respectively) and dapagliflozin at 1 ​μM and 10 ​μM (p ​= ​0.0286 and p ​= ​0.0009, respectively). Interestingly, for canagliflozin, statistical significance was observed only at the higher concentration of 10 ​μM (p ​= ​0.0057).

SGLT2 inhibitors may have a protective effect against cholesterol complex accumulation in HAoSMCs. There were no significant differences between the doses and types of SGLT2 inhibitors; however, dapagliflozin and empagliflozin showed a significant effect regardless of the concentration, while canagliflozin only at higher concentration.