Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits.

Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. Research Abstract Details 

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Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. Abstract Text:

Lee A Morehouse,Eliot D Sugarman,Patricia-Ann Bourassa,Thomas M Sand,Francesca Zimetti,Feng Gao,George H Rothblat,Anthony J Milici,

Cholesteryl ester transfer protein (CETP) inhibitors increase high density lipoprotein-cholesterol (HDL-C) in animals and humans, but whether CETP inhibition will be antiatherogenic is still uncertain. We tested the CETP inhibitor torcetrapib in rabbits fed an atherogenic diet at a dose sufficient to increase HDL-C by at least 3-fold (207 +/- 32 vs. 57 +/- 6 mg/dl in controls at 16 weeks). CETP activity was inhibited by 70-80% throughout the study. Non-HDL-C increased in both groups, but there was no difference apparent by the study's end. At 16 weeks, aortic atherosclerosis was 60% lower in torcetrapib-treated animals (16.4 +/- 3.4% vs. 39.8 +/- 5.4% in controls) and aortic cholesterol content was reduced proportionally. Sera from a separate group of rabbits administered torcetrapib effluxed 48% more cholesterol from Fu5AH cells than did sera from control animals, possibly explaining the reduced aortic cholesterol content. Regression analyses indicated that lesion area in the torcetrapib-treated group was strongly correlated with the ratio of total plasma cholesterol to HDL-C but not with changes in other lipid or lipoprotein levels. CETP inhibition with torcetrapib retards atherosclerosis in rabbits, and the reduced lesion area is associated with increased levels of HDL-C.

Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. Publishing Authors By Initials

LA Morehouse,ED Sugarman,PA Bourassa,TM Sand,F Zimetti,F Gao,GH Rothblat,AJ Milici,

For similar investigative techniques: epidemiologic methods: statistics as topic: regression analysis research abstracts see: investigative techniques: epidemiologic methods: statistics as topic: regression analysis research

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Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of lipid research

VOLUME: 48

Page Numbers: 1263-72

Journal Abbreviation: J. Lipid Res.

ISSN: 0022-2275

DAY: 26

MONTH: 02

YEAR: 2007

Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. Information

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LANGUAGE: eng

NlmUniqueID: 376606

Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. Keywords Mesh Terms:

KEYWORDS: Regression Analysis

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. Information

Substance Name: Cholesterol

Registry Number: 57-88-5

Grant and Affiliation Information for Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits.

AFFILIATION: Department of Cardiovascular and Metabolic and Endocrine Diseases, Pfizer Global Research and Development, Groton, CT. lee.a.morehouse@pfizer.com

Country: United States

AGENCY: United States NHLBI

GRANT: HL 63768

ACRONYM: HL

MEDLINETA: J Lipid Res

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