title: Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats.
abstract: Moderate consumption of red wine reduces risk of death from cardiovascular disease. The polyphenols in red wine are ultimately responsible for this effect, exerting antiatherogenic actions through their antioxidant capacities and modulating intracellular signaling pathways and transcriptional activities. Lipoprotein metabolism is crucial in atherogenesis, and liver is the principal organ controlling lipoprotein homeostasis. This study was intended to identify the primary effects of procyanidins, the most abundant polyphenols in red wine, on both plasma lipoprotein profile and the expression of genes controlling lipoprotein homeostasis in the liver. We show that procyanidins lowered plasma triglyceride, free fatty acids, apolipoprotein B (apoB), LDL-cholesterol and nonHDL:nonLDL-cholesterol levels and slightly increased HDL-cholesterol. Liver mRNA levels of small heterodimer partner (SHP), cholesterol 7alpha-hydroxylase (CYP7A1), and cholesterol biosynthetic enzymes increased, whereas those of apoAII, apoCI, and apoCIII decreased. Lipoprotein lipase (LPL) mRNA levels increased in muscle and decreased in adipose tissue. In conclusion, procyanidins improve the atherosclerotic risk index in the postprandial state, inducing in the liver the overexpression of CYP7A1 (suggesting an increase of cholesterol elimination via bile acids) and SHP, a nuclear receptor emerging as a key regulator of lipid homeostasis at the transcriptional level. These results could explain, at least in part, the beneficial long-term effects associated with moderate red wine consumption.
authors.affiliation: Departament de Bioquímica i Biotecnologia. CeRTA. Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Del Bas
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Larrea
authors.forename: Mayte
authors.initials: M
authors.lastname: Blay
authors.forename: Anna
authors.initials: A
authors.lastname: Ardèvol
authors.forename: Maria Josepa
authors.initials: MJ
authors.lastname: Salvadó
authors.forename: Lluis
authors.initials: L
authors.lastname: Arola
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
mesh_terms: D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics; D053302:Apolipoprotein C-I; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000097:blood; D001056:Apolipoproteins C / Q000235:genetics; D001161:Arteriosclerosis / Q000517:prevention & control; D002784:Cholesterol / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D002788:Cholesterol Esters / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015870:Gene Expression; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012639:Seeds / Q000737:chemistry*; D014280:Triglycerides / Q000032:analysis / Q000097:blood; D027843:Vitis / Q000737:chemistry*; D014920:Wine / Q000032:analysis
chemical_list: D016633:Apolipoprotein A-II; D053302:Apolipoprotein C-I; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D044945:Proanthocyanidins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014280:Triglycerides; C099713:nuclear receptor subfamily 0, group B, member 2; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase