Modulation peroxisome proliferators activated receptor alpha (PPAR alpha) and acyl coenzyme A: cholesterol acyltransferase1 (ACAT1) gene expression by fatty acids in foam cell.
BACKGROUND
One of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as peroxisome proliferators activated receptors (PPARs) and acyl coenzyme A: cholesterol acyltransferase1 (ACAT1) are involved in cholesterol homeostasis. Fatty acids are important ligands of PPARalpha and the concentration of them can effect expression of ACAT1. So this study designed to clarified on the role of these genes and fatty acids on the lipid metabolism in foam cells.


METHODS
This study examined effects of c9, t11-conjugated linoleic acid(c9, t11-CLA), alpha linolenic acid (LA), eicosapentaenoic acid (EPA) on the PPARalpha and ACAT1 genes expression by using Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells.


RESULTS
Incubation of c9, t11-CLA, LA cause a significant reduction in intracellular total cholesterol, free cholesterol, cellular and esterified cholesterol concentrations (P < or = 0.05). CLA and LA had no significant effect on the mRNA levels of ACAT1, but EPA increased ACAT1 mRNA expression (P = 0.003). Treatment with EPA increased PPARalpha mRNA levels (P < or = 0.001), although CLA, LA had no significant effect on PPARalpha mRNA expression.


CONCLUSIONS
In conclusion, it seems that different fatty acids have different effects on gene expression and lipid metabolism and for complete conception study of the genes involved in lipid metabolism in foam cell all at once maybe is benefit.
Reza
Javad Zavvar
JZ
Department of Medical Biochemistry, Faculty of medicine, Tehran University of Medical Scenses, Tehran, Iran.
Doosti
Mahmoud
M
Salehipour
Masoud
M
Packnejad
Malehieh
M
Mojarrad
Majed
M
Heidari
Mansour
M
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002785:Sterol O-Acyltransferase / Q000235:genetics*; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
D044243:Linoleic Acids, Conjugated; D047492:Peroxisome Proliferator-Activated Receptors; D017962:alpha-Linolenic Acid; D002784:Cholesterol; D015118:Eicosapentaenoic Acid; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1