Related Experiment Video
Updated: Jun 1, 2026
LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
Effect of sulfonylurea agents on reverse cholesterol transport in vitro and vivo
Yoshio Terao1, Makoto Ayaori, Masatsune Ogura
1Division of Anti-aging, Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Insights
Sulfonylurea agents (SUAs) like glibenclamide can inhibit cholesterol transport proteins at high doses. However, lower doses do not adversely affect cholesterol efflux or reverse cholesterol transport in vivo.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Pharmacology
Background:
- Reverse cholesterol transport (RCT) is crucial for HDL's anti-atherogenic effects.
- Sulfonylurea agents (SUAs) like glibenclamide may impair HDL function by inhibiting ATP binding-cassette transporter A1 (ABCA1).
- The in vivo impact of SUAs on RCT remains unclear.
Purpose of the Study:
- To investigate the effects of glibenclamide and glimepiride on ABCA1, ABCG1, and scavenger receptor class B type I (SR-BI) in macrophages.
- To determine the impact of these SUAs on overall RCT in vivo.
Main Methods:
- In vitro studies utilized RAW264.7, HEK293, and BHK-21 cell lines.
- In vivo RCT was assessed by injecting 3H-cholesterol-labeled cells into mice.
Main Results:
- High-dose glibenclamide inhibited ABCA1 function, apoA-I-mediated cholesterol efflux, and ABCA1 expression.
- Both glibenclamide and glimepiride inhibited ABCA1 and SR-BI-mediated cholesterol efflux at high doses.
- High doses increased ABCG1 expression, promoting HDL-mediated efflux independently of ABCG1.
- Low doses of SUAs did not affect cholesterol efflux or RCT in mice, despite increasing ABCA1/G1 expression.
Conclusions:
- High doses of SUAs inhibit ABCA1 and SR-BI functionality, but not ABCG1.
- Lower doses of SUAs demonstrate no adverse effects on cholesterol efflux or RCT in vivo.
- These findings suggest SUAs may not adversely affect atherosclerosis, contrasting with prior glibenclamide research.
Aim:
Reverse cholesterol transport (RCT) is a critical mechanism for the anti-atherogenic property of HDL. The inhibitory effect of the sulfonylurea agent (SUA) glibenclamide on ATP binding-cassette transporter (ABC) A1 may decrease HDL function but it remains unclear whether it attenuates RCT in vivo. We therefore investigated how the SUAs glibenclamide and glimepiride affected the functionality of ABCA1/ABCG1 and scavenger receptor class B type I (SR-BI) expression in macrophages in vitro and overall RCT in vivo.
Methods:
RAW264.7, HEK293 and BHK-21 cells were used for in vitro studies. To investigate RCT in vivo, 3H-cholesterol-labeled and acetyl LDL-loaded RAW264.7 cells were injected into mice.
Results:
High dose (500µM) of glibenclamide inhibited ABCA1 function and apolipoprotein A-I (apoA-I)-mediated cholesterol efflux, and attenuated ABCA1 expression. Although glimepiride maintained apoA-I-mediated cholesterol efflux from RAW264.7 cells, like glibenclamide, it inhibited ABCA1-mediated cholesterol efflux from transfected HEK293 cells. Similarly, the SUAs inhibited SR-BI-mediated cholesterol efflux from transfected BHK-21 cells. High doses of SUAs increased ABCG1 expression in RAW264.7 cells, promoting HDL-mediated cholesterol efflux in an ABCG1-independent manner. Low doses (0.1-100 µM) of SUAs did not affect cholesterol efflux from macrophages despite dose-dependent increases in ABCA1/G1 expression. Furthermore, they did not change RCT or plasma lipid levels in mice.
Conclusion:
High doses of SUAs inhibited the functionality of ABCA1/SR-BI, but not ABCG1. At lower doses, they had no unfavorable effects on cholesterol efflux or overall RCT in vivo. These results indicate that SUAs do not have adverse effects on atherosclerosis contrary to previous findings for glibenclamide.
Related Concept Videos
01:17Oral Hypoglycemic Agents: Sulfonylureas
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:16Methods for Studying Drug Absorption: In vitro
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
01:09Methods for Studying Drug Absorption: In situ
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are typically...
01:06Oral Hypoglycemic Agents: Glinides