Polyunsaturated Fatty Acids and Modulation of Cholesterol Homeostasis in THP-1 Macrophage-Derived Foam Cells

Masoud Salehipour,Javad Zavvar Reza,Mansour Heidari,Mahmoud Doosti,Ebrahim Javadi,Shahla Rezaei,Malihe Paknejad,Naser Nejadi

doi:10.3390/ijms11114660

Abstract

Transformation of macrophages to foam cells is determined by the rates of cholesterol uptake and efflux. This study uses a real time RT-PCR technique to investigate the role of conjugated linoleic acid (CLA), α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) in the regulation of the ATP-binding cassette A1 (ABCA1) and liver X receptor α (LXR) genes, which are involved in cholesterol homeostasis. Accordingly, these fatty acids significantly reduced the total, free and esterified cholesterols within the foam cells. While the expression of the ABCA1 and LXRα genes was increased in the presence of the pharmacological LXRα ligand, T0901317, their mRNA expression was not significantly affected by CLA, ALA and EPA. These results suggest that although polyunsaturated fatty acids have an effect on cholesterol homeostasis, they cannot change the expression of the ABCA1 and LXRα genes. Alternatively, several other genes and proteins may be involved.

Highlights

Accumulation of cholesterol in the walls of arteries provides the possibility of the uptake of modified low-density lipoprotein (m-LDL) by macrophages and promotes a local pro-inflammatory response leading to a pathologic condition known as atherosclerosis [1]
XTT assay was performed in the presence of the different fatty acids conjugated linoleic acid (CLA), ALA and eicosapentaenoic acid (EPA), in addition to T0901317 as the LXRα ligand
The results showed that fatty acids and T091317 have no adverse effect on the viability of THP-1 cell line, in comparison with control group (Figure 1)

Summary

Introduction

Accumulation of cholesterol in the walls of arteries provides the possibility of the uptake of modified low-density lipoprotein (m-LDL) by macrophages and promotes a local pro-inflammatory response leading to a pathologic condition known as atherosclerosis [1]. The balance of cholesterol uptake and efflux in macrophages is a determining factor towards the formation of foam cells, which play a key role in the initiation and progression of atherosclerosis. Numerous genes and proteins, such as ATP-binding cassette A1 (ABCA1), liver X receptors (LXRs), sreol regulatory element binding proteins (SREBPs) and Peroxisome proliferator-activated receptors (PPARs), are involved in the process of foam cell formation, and study of these factors and their regulatory mechanisms is of great value for the prevention of cardiovascular disease (CVD). ABCA1 belongs to the large ATP-binding cassette transporter family. These transmembrane proteins transport cholesterol and phospholipids to lipid-free or lipid-poor apolipoprotein A-I (apoA-I). ABCA1, whose function is defective in Tangier disease, is a pivotal protein in regulation of plasma HDL-cholesterol levels and cellular cholesterol homeostasis [2,3,4,5]

Methods

Results

Conclusion