HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wrenn, S. M. Articles by Rudel, L. L. Search for Related Content PubMed PubMed Citation Articles by Wrenn, S. M., Jr Articles by Rudel, L. L. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 36, 1199-1210, Copyright © 1995 by Lipid Research, Inc.

ARTICLES

ACAT inhibitors CL 283,546 and CL 283,796 reduce LDL cholesterol without affecting cholesterol absorption in African green monkeys

SM Wrenn Jr, JS Parks, FW Immermann and LL Rudel
Lederle Laboratories, Medical Research Division, American Cyanamid Co., Pearl River, NY 10965, USA.

Previous studies with a number of selective acylcoenzyme A:cholesterol acyltransferase (ACAT) inhibitors in several animal models have demonstrated significant reductions in plasma cholesterol and, in some studies, triglyceride levels. This study was conducted to examine the effects of two ACAT inhibitors, CL 283,546 and CL 283,796, in cholesterol-high fat diet fed African green monkeys, a relevant primate model of hyperlipidemia and coronary artery atherosclerosis. Treatment with CL 283,546 or CL 283,796 resulted in significant reductions (ca. 25-30%) in total plasma cholesterol at both 10 and 30 mg/kg per day doses. This reduction in plasma cholesterol was due almost entirely to reduction in low density lipoprotein (LDL) cholesterol (ca. 45%) without significantly affecting high density lipoprotein (HDL) cholesterol, very low density lipoprotein + intermediate density lipoprotein (VLDL + IDL) cholesterol, or triglyceride concentrations. There were no significant effects on plasma concentrations of apolipoproteins A-I, E, or B and, thus, the reduction seen in LDL cholesterol appears to be due to a diminished cholesterol content of LDL particles. Our studies revealed that treatment with these compounds did not reduce cholesterol absorption, which was somewhat surprising as ACAT inhibitors are generally thought to exert their hypolipidemic effects, at least in part, by inhibition of intestinal cholesterol absorption. Our data are consistent with a principal activity of these drugs on the liver to reduce cholesteryl ester secretion in VLDL, leading to a diminished LDL-cholesterol content, and, presumably, enhanced biliary cholesterol-bile acid excretion.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Ye, Y. Huang, K. Mullendorff, L. Dong, G. Giedt, E. C. Meng, F. E. Cohen, I. D. Kuntz, K. H. Weisgraber, and R. W. Mahley Apolipoprotein (apo) E4 enhances amyloid {beta} peptide production in cultured neuronal cells: ApoE structure as a potential therapeutic target PNAS, December 20, 2005; 102(51): 18700 - 18705. [Abstract] [Full Text] [PDF]

				Z. Zhang, W. K. K. Ho, Y. Huang, A. E. James, L. W. Lam, and Z.-Y. Chen Hawthorn Fruit Is Hypolipidemic in Rabbits Fed a High Cholesterol Diet J. Nutr., January 1, 2002; 132(1): 5 - 10. [Abstract] [Full Text] [PDF]

				P. T. Chan, W. P. Fong, Y. L. Cheung, Y. Huang, W. K. K. Ho, and Z.-Y. Chen Jasmine Green Tea Epicatechins Are Hypolipidemic in Hamsters (Mesocricetus auratus) Fed a High Fat Diet J. Nutr., June 1, 1999; 129(6): 1094 - 1101. [Abstract] [Full Text]

				O. Lee, C. C. Y. Chang, W. Lee, and T.-Y. Chang Immunodepletion experiments suggest that acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) protein plays a major catalytic role in adult human liver, adrenal gland, macrophages, and kidney, but not in intestines J. Lipid Res., August 1, 1998; 39(8): 1722 - 1727. [Abstract] [Full Text]