GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules

• Main Authors: Ying Yang, Yi-Tian Lian, Shi-Yuan Huang, Yong Yang, Long-Xian Cheng, Kun Liu
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2014-04-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Macrophage; Atherosclerosis; GABA; GABA receptor agonist; Cholesterol
• Online Access: http://www.karger.com/Article/FullText/358681
• ISSN: 1015-8987; 1421-9778

Aims: γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs). Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL)-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.