title: Lycopene regulation of cholesterol synthesis and efflux in human macrophages.
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.
authors.affiliation: Institute of General Pathology, Catholic University School of Medicine, Rome, Italy. p.palozza@rm.unicatt.it
authors.forename: Paola
authors.initials: P
authors.lastname: Palozza
authors.forename: Rossella
authors.initials: R
authors.lastname: Simone
authors.forename: Assunta
authors.initials: A
authors.lastname: Catalano
authors.forename: Nadia
authors.initials: N
authors.lastname: Parrone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monego
authors.forename: Franco O
authors.initials: FO
authors.lastname: Ranelletti
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D000077276:Lycopene; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D051242:Caveolin 1; D047495:PPAR gamma; D002338:Carotenoids; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D000077276:Lycopene