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Titolo:
Squalene synthase inhibitors reduce plasma triglyceride through a low-density lipoprotein receptor-independent mechanism
Autore:
Hiyoshi, H; Yanagimachi, M; Ito, M; Saeki, T; Yoshida, I; Okada, T; Ikuta, H; Shinmyo, D; Tanaka, K; Kurusu, N; Tanaka, H;
Indirizzi:
Eisai & Co Ltd, Tsukuba Res Labs, Tsukuba, Ibaraki 3002635, Japan Eisai & Co Ltd Tsukuba Ibaraki Japan 3002635 kuba, Ibaraki 3002635, Japan
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 3, volume: 431, anno: 2001,
pagine: 345 - 352
SICI:
0014-2999(20011123)431:3<345:SSIRPT>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HMG-COA REDUCTASE; CORONARY-ARTERY DISEASE; WHHL-RABBIT; FAMILIAL HYPERCHOLESTEROLEMIA; ANIMAL-MODEL; B PRODUCTION; RISK FACTOR; CHOLESTEROL; PRAVASTATIN; ATHEROSCLEROSIS;
Keywords:
squalene synthase inhibitor; triglyceride; low-density lipoprotein (LDL) receptor; WHHL; rabbit; hypertriglyceridemia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Hiyoshi, H Eisai & Co Ltd, Tsukuba Res Labs, Tokodai 5-1-3, Tsukuba, Ibaraki 3002635,Japan Eisai & Co Ltd Tokodai 5-1-3 Tsukuba Ibaraki Japan 3002635apan
Citazione:
H. Hiyoshi et al., "Squalene synthase inhibitors reduce plasma triglyceride through a low-density lipoprotein receptor-independent mechanism", EUR J PHARM, 431(3), 2001, pp. 345-352

Abstract

Inhibitors of squalene synthase are considered to be candidate drugs to reduce both plasma cholesterol and triglyceride. However, little is known about the mechanism of squalene synthase inhibitor-specific effect on plasma triglyceride. In this study, we confirmed the triglyceride-lowering effect of ER-27856, a potent squalene synthase inhibitor prodrug, in rhesus monkeys. To determine the role of low-density lipoprotein (LDL) receptor in the triglyceride-lowering effect of squalene synthase inhibitors, we intravenously administered ER-28448, the active form of ER-27856, to Watanabe heritablehyperlipidemic (WHHL) rabbits for 4 days. In heterozygotes, ER-28448 reduced plasma cholesterol and triglyceride by 52% and 37%, respectively. In homozygous rabbits, in contrast, ER-28448 lowered plasma triglyceride by 40% but did not lower plasma cholesterol. Orally administered ER-27856 reduced plasma triglyceride in homozygous animals but atorvastatin and bezafibrate did not. In hepatocytes isolated from homozygous WHHL rabbits, squalene synthase inhibitors but not atorvastatin reduced triglyceride biosynthesis. These data demonstrate that squalene synthase inhibitors reduced plasma triglyceride through an LDL receptor-independent mechanism, which was distinct from that of the triglyceride-lowering action of atorvastatin or bezafibrate. The reduction of hepatic triglyceride biosynthesis may play an important role in the hypotrigyceridemic action of squalene synthase inhibitors. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 18:27:54