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Titolo:
EFFECTS OF DIFFERENT PHENOTYPES OF HYPERLIPOPROTEINEMIA AND OF TREATMENT WITH FIBRIC ACID-DERIVATIVES ON THE RATES OF CHOLESTEROL 7-ALPHA-HYDROXYLATION IN HUMANS
Autore:
BERTOLOTTI M; CONCARI M; LORIA P; ABATE N; PINETTI A; GUICCIARDI ME; CARULLI N;
Indirizzi:
UNIV MODENA POLICLIN,IST PATOL MED,VIA POZZO 71 I-41100 MODENA ITALY UNIV MODENA,DEPT CHEM I-41100 MODENA ITALY UNIV MODENA,DEPT INTERNAL MED I-41100 MODENA ITALY
Titolo Testata:
Arteriosclerosis, thrombosis, and vascular biology
fascicolo: 8, volume: 15, anno: 1995,
pagine: 1064 - 1069
SICI:
1079-5642(1995)15:8<1064:EODPOH>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL COMBINED HYPERLIPIDEMIA; DENSITY-LIPOPROTEIN RECEPTOR; BILIARY LIPID SECRETION; PHARMACOKINETIC PROPERTIES; NORMOLIPEMIC SUBJECTS; URSODEOXYCHOLIC ACID; THERAPEUTIC USE; METABOLISM; HYPERCHOLESTEROLEMIA; HYPERTRIGLYCERIDEMIA;
Keywords:
FAMILIAL HYPERCHOLESTEROLEMIA; FAMILIAL COMBINED HYPERLIPIDEMIA; BILE ACID SYNTHESIS; GEMFIBROZIL; BEZAFIBRATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
M. Bertolotti et al., "EFFECTS OF DIFFERENT PHENOTYPES OF HYPERLIPOPROTEINEMIA AND OF TREATMENT WITH FIBRIC ACID-DERIVATIVES ON THE RATES OF CHOLESTEROL 7-ALPHA-HYDROXYLATION IN HUMANS", Arteriosclerosis, thrombosis, and vascular biology, 15(8), 1995, pp. 1064-1069

Abstract

Little is known about the relationships between hyperlipidemia and bile acid metabolism. However, hypolipidemic treatment with fibric acid derivatives has been shown to increase biliary cholesterol secretion, presumably by reducing bile acid synthesis. To clarify such relationships, we investigated the effects of different hyperlipoproteinemic conditions and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation (the limiting step of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years) with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous familial hypercholesterolemia, a condition of reduced activity of LDL receptors, and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and clinical diagnosis of familial combined hyperlipidemia, a condition probably related to increased hepatic lipoprotein synthesis. Cholesterol 7 alpha-hydroxylation rates were assayed in vivo by tritium release assay after an intravenous injection of [7 alpha-H-3]cholesterol. The results were compared by ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to 83 years), with age as the covariate. Six patients were also studied after treatmentwith gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks). Hydroxylation rates were 0.82 +/- 0.22 mmol/d in the familial hypercholesterolemia group and 1.30 +/- 0.47 mmol/d in the familial combined hyperlipidemia. group (P < .05 between the two groups and between patients with familial combined hyperlipidemia and control subjects; P = NS between patients with familial hypercholesterolemia and control subjects, as determined by ANOVA). Treatment with both gemfibrozil and bezafibrate reduced serum cholesterol, slightly increased HDL cholesterol, and significantly reduced serum triglyceride and apo B concentrations. Cholesterol 7 alpha-hydroxylation rates were significantly reduced by nearly 55% both after gemfibrozil and after bezafibrate. Our findings indirectly suggest that cholesterol degradation to bile acid is independent of receptor-mediated uptake of LDL by the liver. Hydroxylation rates seem to parallel serum levels of triglyceride and apo B (particularly after fibrate treatment), possibly suggesting a coordinate reg ulation of bile acid and lipoprotein synthesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 03:07:18