Lycopene regulation of cholesterol synthesis and efflux in human macrophages

作者：Palozza Paola^*; Simone Rossella; Catalano Assunta; Parrone Nadia; Monego Giovanni; Ranelletti Franco O

来源：Journal of Nutritional Biochemistry, 2011, 22(10): 971-978.

DOI：10.1016/j.jnutbio.2010.08.010

• Lycopene
• Cholesterol
• HMG-CoA reductase
• ABCA1
• Caveolin-1
• THP-1 cells

Hypercholesterolemia is one of the most important risk factors for atherosclerosis, and tomato lycopene has been suggested to have beneficial effects against such a disease, although the exact molecular mechanism is unknown. We tested the hypothesis that lycopene may exert its antiatherogenic role through changes in cholesterol metabolism. Incubation of THP-1 cells with lycopene (0.5-2 mu M) dose-dependently reduced intracellular total cholesterol. Such an effect was associated with a decrease in reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase expression and with an increase in ABCA1 and caveolin-1 (cav-1) expressions. In addition, lycopene enhanced RhoA levels in the cytosolic fraction, activating peroxisome proliferator-activated receptor gamma (PPAR gamma) and liver X receptor alpha expressions. Concomitant addition of lycopene and the PPAR gamma inhibitor GW9662 or lycopene and mevalonate blocked the carotenoid-induced increase in ABCA1 and cav-1 expressions. These results imply a potential role of lycopene in attenuating foam cell formation and, therefore, in preventing atherosclerosis by a cascade mechanism involving inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, RhoA inactivation and subsequent increase in PPAR gamma and liver X receptor alpha activities and enhancement of ABCA1 and cav-1 expressions.

• 出版日期2011-10