ABSTRACT
Cardiovascular disease [CVD] is the leading cause of death and disability in developed countries. Atherosclerosis is the major cause of CVD, accounting for about half of the attributed deaths. Cholesterol homeostasis is one of the most important factors in atherosclerosis. ATP-Binding cassette transporters cholesterol. Omega [omega] 3 fatty acids are important ligands for regulation of ABC transporters such as ABCG1. Concern has been raised that the low absolute intakes of EPA and high ratios of omega -6 polyunsaturated fatty acids [omega-6 PUFA] to EPA may predispose some individuals to CVD. Eicosapentaenoic acid [EPA] is the most abundant omega 3 fatty acid in the diet. The objective of this study was to evaluate the effect of different concentrations of EPA on the expression of ABCG1 gene in the human monocyte THP-1 cells. In this study, THP-1 cells were cultured in RPMI 1640 medium, THP-1 monocytes were then differentiated to macrophages with PMA [phorbol myristic acid] and stimulated with 50, 75 and 100 micro M of EPA for 24 h at 37°C. We examined the effects of EPA treatment on the expression of ABCG1 gene using Quantitative Real time RT-PCR [qRT-PCR]. Our results, indicate that ABCG1 mRNA expression was significantly reduced by 50, 75 and 100 micro M EPA fatty acid treatments as compared to the control cells [p = 0.009, p < 0.001 and p = 0.002, respectively]. These results suggest that polyunsaturated fatty acids [PUFAs] such as EPA have an effect on the cholesterol homeostasis in macrophages, and they can change the expression of ABCG1 gene. It seems that EPA has different effects on gene expression and lipid metabolism
ABSTRACT
Background: there is evidence that CD36 promotes foam cell formation through internalizing oxidized LDL [ox- LDL] into macrophages; therefore, it plays a key role in pathogenesis of atherosclerosis. In addition, CD36 expression seems to be mediated by nuclear receptor peroxisome proliferator-activated receptor gamma [PPAR-[gamma]]. The aim of the present study was to evaluate and compare the effect of PPAR-[gamma] ligands, eicosapentaenoic acid [EPA] as an anti-atherogenic factor and ox-LDL as an atherogenic factor on CD36 expression. Mechanism of PPAR-[gamma] action and its ligands in CD36 expression were also investigated
Methods: raw 264.7 macrophage cell line was treated with ox-LDL [100 and 150 [micro]g protein/LDL] and EPA [100 and 200 [micro]M] for 24 and 48 hours in absence or presence of PPAR-[gamma] inhibitor, T0070907. Quantitative real-time PCR and Western-blotting were used for analysis of gene and protein expression, respectively
Results: raw 264.7 exposures to ox-LDL and EPA resulted in increased expression of CD36 mRNA and protein; however, mRNA and PPAR-[gamma] protein were not upregulated significantly. Pre-incubation of cells with T0070907 led to decreased expression of CD36 when treated with ox-LDL and EPA
Conclusion: it was confirmed that both EPA and ox-LDL increased CD36 expression but not PPAR-[gamma], and also co-treatment with PPAR-[gamma] inhibitor decreased CD36 expression. We concluded that upregulation of CD36 depends on PPAR-[gamma] activation and is not related to increased expression of PPAR-[gamma]. Induction of CD36 by EPA showed that CD36 suppression is not the means by which [omega]-3 fatty acids [EPA] provide protection against formation of atherosclerotic plaque. Iran. Biomed. J. 17 [2]: 84-92, 2013
ABSTRACT
Several dietary factors are involved in cardiovascular coronary heart diseases, including trans fatty acids, which are generally formed during hydrogenation of vegetable oils, a process that causes conversion of liquid oils into semisolid fats. Nowadays, it is well-known that trans fatty acids form a major risk factor in the occurrence and progression of atherosclerosis. On the other hand, it has been identified that some nuclear receptors, such as PPARs, are involved and play important roles in lipid homeostasis and pathogenesis of cardiovascular diseases. Therefore, we studied the effect of elaidic acid on gene expression of peroxisome proliferator activated receptor gamma [PPARgamma]. Murine macrophage RAW264.7 cells were treated by 0.5, 1, and 2 mM concentrations of elaidic acid for 6 h. The control group was treated by 50% ethanol [as solvent], equivalent to the amount of ethanol used in 2 mM concentration of elaidic acid. Later, the total RNA was extracted and its cDNA was synthesized. Finally, the quantity of PPARgamma gene expression was measured by real-time PCR. Overall, 0.5, 1, and 2 mM concentrations of elaidic acid decreased PPARgamma gene expression in RAW264.7 macrophage cell line by -1.36, -1.68, and -3.24 folds compared with the control group, respectively. By decreasing the expression of nuclear receptor PPARgamma, elaidic acid causes, intensifies or accelerates the occurrence of cardiovascular diseases, especially atherosclerosis. This finding shows the importance of reducing the consumption of elaidic acid containing foods