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Journal of Lipid Research, Vol. 44, 1224-1231, June 2003
Copyright © 2003 by Lipid Research, Inc.

PPAR and PPAR activators suppress the monocyte-macrophage apoB-48 receptor¹

Go Haraguchi^*, Yasushi Kobayashi^*, Matthew L. Brown, Akira Tanaka, Mitsuaki Isobe^*, Sandra H. Gianturco^2, and William A. Bradley^2,

^* Tokyo Medical and Dental University, Department of Cardiovascular Medicine, Tokyo 113-8519, Japan
University of Alabama at Birmingham, Department of Medicine, Division of Gerontology and Geriatric Medicine, Birmingham, AL 35294-0012
Kanto Gakuin University, Department of Health and Nutrition, College of Human and Environmental Studies, Yokohama 236-8501, Japan

² To whom correspondence should be addressed. e-mail: wbradley{at}uab.edu, shg{at}ucb.edu

Certain triglyceride-rich lipoproteins (TRLs), specifically chylomicrons, dyslipemic VLDLs, and their remnants, are atherogenic and can induce monocyte-macrophage foam cell formation in vitro via the apolipoprotein B-48 receptor (apoB-48R). Human atherosclerotic lesion foam cells express the apoB-48R, as determined immunohistochemically, suggesting it can play a role in the conversion of macrophages into foam cells in vivo. The regulation of the apoB-48R in monocyte-macrophages is not fully understood, albeit previous studies indicated that cellular sterol levels and state of differentiation do not affect apoB-48R expression. Since peroxisome proliferator-activated receptors (PPARs) regulate some aspects of cellular lipid metabolism and may be protective in atherogenesis by up-regulation of liver X-activated receptor and ATP-binding cassette transporter A1, we examined the regulation of apoB-48R by PPAR ligands in human monocyte-macrophages. Using real-time PCR, Northern, Western, and functional cellular lipid accumulation assays, we show that PPAR and PPAR activators significantly suppress the expression of apoB-48R mRNA in human THP-1 and blood-borne monocyte-macrophages. Moreover, PPAR activators inhibit the expression of the apoB-48R protein and, notably, the apoB-48R-mediated lipid accumulation of TRL by THP-1 monocytes in vitro.

If PPAR activators also suppress the apoB-48R pathway in vivo, diminished apoB-48R-mediated monocyte-macrophage lipid accumulation may be yet another antiatherogenic effect of the action of PPAR ligands.

Supplementary key words lipoproteins • triglyceride • atherosclerosis • apolipoprotein B • foam cells • peroxisome proliferator-activated receptor

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