Lycopene regulation of cholesterol synthesis and efflux in human macrophages.

Giovanni Monego, Paola Palozza, Rossella Emanuela Simone, Assunta Catalano, Franco Oreste Ranelletti

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60 Citazioni (Scopus)

Abstract

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 μM) 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 (PPARγ) and liver X receptor alpha expressions. Concomitant addition of lycopene and the PPARγ 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 PPARγ and liver X receptor alpha activities and enhancement of ABCA1 and cav-1 expressions.
Lingua originaleEnglish
pagine (da-a)971-978
Numero di pagine8
RivistaJournal of Nutritional Biochemistry
Stato di pubblicazionePubblicato - 2011

Keywords

  • ABCA1
  • HMGCoA-reductase
  • THP-1
  • caveolin 1
  • cholesterol
  • lycopene

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