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Titolo:
Overexpression of apolipoprotein E3 in transgenic rabbits causes combined hyperlipidemia by stimulating hepatic VLDL production and impairing VLDL lipolysis
Autore:
Huang, YD; Ji, ZS; Brecht, WJ; Rall, SC; Taylor, JM; Mahley, RW;
Indirizzi:
Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA94141 USA Univ Calif San Francisco San Francisco CA USA 94141 rancisco, CA94141 USA Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94141 USAUniv Calif San Francisco San Francisco CA USA 94141 ancisco, CA 94141 USA Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94141 USA Univ Calif San Francisco San Francisco CA USA 94141 ancisco, CA 94141 USA Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94141 USA Univ Calif San Francisco San Francisco CA USA 94141 ancisco, CA 94141 USA Univ Calif San Francisco, Dept Med, San Francisco, CA 94141 USA Univ CalifSan Francisco San Francisco CA USA 94141 ancisco, CA 94141 USA
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 12, volume: 19, anno: 1999,
pagine: 2952 - 2959
SICI:
1079-5642(199912)19:12<2952:OOAEIT>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY LIPOPROTEINS; FAMILIAL COMBINED HYPERLIPIDEMIA; HEPARAN-SULFATE PROTEOGLYCANS; LIPASE-MEDIATED LIPOLYSIS; B-CONTAINING LIPOPROTEINS; IN-VIVO; III HYPERLIPOPROTEINEMIA; TRIGLYCERIDE; PLASMA; MICE;
Keywords:
apoB; lipoprotein lipase; VLDL clearance; hypertriglyceridemia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Huang, YD Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, POB 419100, San Francisco, CA 94141 USA Univ Calif San Francisco POB 419100 San Francisco CA USA 94141 A
Citazione:
Y.D. Huang et al., "Overexpression of apolipoprotein E3 in transgenic rabbits causes combined hyperlipidemia by stimulating hepatic VLDL production and impairing VLDL lipolysis", ART THROM V, 19(12), 1999, pp. 2952-2959

Abstract

The differential effects of overexpression of human apolipoprotein (apo) E3 on plasma cholesterol and triglyceride metabolism were investigated in transgenic rabbits expressing low (10 mg/dL), medium (10 to 20 mg/dL), or high (>20 mg/dL) levels of apoE3. Cholesterol levels increased progressively with increasing levels of apoE3, whereas triglyceride levels were not significantly affected at apoE3 levels up to 20 mg/dL but were markedly increasedat levels of apoE3 >20 mg/dL. The medium expressers had marked hypercholesterolemia (up to 3- to 4-fold over nontransgenics), characterized by an increase in low density lipoprotein (LDL) cholesterol, while the low expressers had only slightly increased plasma cholesterol levels. The medium expressers displayed an 18-fold increase in LDL but also had a 2-fold increase in hepatic very low density lipoprotein (VLDL) triglyceride production, an 8-fold increase in VLDL apoB, and a moderate decrease in the ability of the VLDL to be lipolyzed. However, plasma clearance of VLDL was increased, likelybecause of the increased apoE3 content. The increase in LDL appears to be due to an enhanced competition of VLDL for LDL receptor binding and uptake,resulting in the accumulation of LDL. The combined hyperlipidemia of the apoE3 high expressers (>20 mg/dL) was characterized by a 19-fold increase inLDL cholesterol but also a 4-fold increase in hepatic VLDL triglyceride production associated with a marked elevation of plasma VLDL triglycerides, cholesterol, and apoB 100 (4-, 9-, and 25-fold over nontransgenics, respectively). The VLDL from the high expressers was much more enriched in apoE3 and markedly depleted in apoC-II, which contributed to a >60% inhibition of VLDL lipolysis. The combined effects of stimulated VLDL production and impaired VLDL Lipolysis accounted for the increases in plasma triglyceride and VLDL concentrations in the apoE3 high expressers. The hyperlipidemic apoE3 rabbits have phenotypes similar to those of familial combined hyperlipidemia, in which VLDL overproduction is a major biochemical feature. Overall, elevated expression of apoE3 appears to determine plasma lipid levels by stimulating hepatic VLDL production, enhancing VLDL clearance, and inhibiting VLDL lipolysis. Thus, the differential expression of apoE may, within a rather narrow range of concentrations, play a critical role in modulating plasmacholesterol and triglyceride levels and may represent an important determinant of specific types of hyperlipoproteinemia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 23:53:46