PPARα and PPARγ activators suppress the monocyte-macrophage apoB-48 receptor1

• Main Authors: Go Haraguchi, Yasushi Kobayashi, Matthew L. Brown, Akira Tanaka, Mitsuaki Isobe, Sandra H. Gianturco, William A. Bradley
• Format: Article
• Language: English
• Published: Elsevier 2003-06-01
• Series: Journal of Lipid Research
• Subjects: lipoproteins; triglyceride; atherosclerosis; apolipoprotein B; foam cells; peroxisome proliferator-activated receptor
• Online Access: http://www.sciencedirect.com/science/article/pii/S002222752031124X

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 α 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 PPARα and PPARγ 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.