SGLT2 inhibitors attenuate cholesterol accumulation in Human Aortic Smooth Muscle Cells

Area of Science:

• Cardiovascular Pharmacology
• Cellular Biology
• Metabolic Disease Research

Background:

• Cholesterol accumulation in Human Aortic Smooth Muscle Cells (HAoSMCs) contributes to atherosclerosis.
• The impact of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors on cellular cholesterol levels remains largely unexplored.

Purpose of the Study:

• To investigate the effect of SGLT2 inhibitors on cholesterol accumulation in HAoSMCs.
• To evaluate potential protective mechanisms of SGLT2 inhibitors against lipid deposition in vascular cells.

Main Methods:

• HAoSMCs were treated with varying concentrations of empagliflozin, dapagliflozin, and canagliflozin.
• Cells were exposed to a cholesterol-methyl-β-cyclodextrin complex to induce lipid accumulation.
• Oil Red O staining quantified lipid content, with absorbance measured at 492 nm.

Main Results:

• Cholesterol complex significantly increased lipid accumulation in HAoSMCs (31.8%).
• SGLT2 inhibitors notably reduced cholesterol-induced lipid accumulation (9.8–18.2%).
• Empagliflozin and dapagliflozin showed significant effects at both tested concentrations, while canagliflozin was significant only at the higher concentration.

Conclusions:

• SGLT2 inhibitors demonstrate a potential protective role against cholesterol accumulation in HAoSMCs.
• The efficacy varied slightly among SGLT2 inhibitors, with empagliflozin and dapagliflozin showing consistent effects.
• These findings may have implications for managing vascular complications in patients treated with SGLT2 inhibitors.