doi: 10.1161/hq1201.099426
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Transforming Growth Factor-ß1 Inhibits Macrophage Cholesteryl Ester Accumulation Induced by Native and Oxidized VLDL Remnants
From the Departments of Medicine and Biochemistry and The John P. Robarts Research Institute at the University of Western Ontario, London, Canada.
Correspondence to Dr Murray W. Huff, The John P. Robarts Research Institute, Room 4-16, 100 Perth Dr, London, Ontario, Canada N6A 5K8. E-mail mhuff{at}uwo.ca
Transforming growth factor ß1 (TGF-ß1) is secreted by various cells, including macrophages, smooth muscle cells, and endothelial cells. TGF-ß1 is present in atherosclerotic lesions, but its role in regulating macrophage foam cell formation is not understood. Hypertriglyceridemic very low density lipoprotein (VLDL) remnants (VLDL-REMs) in their native or oxidized form will induce cholesteryl ester (CE) and triglyceride (TG) accumulation in macrophages. Therefore, we examined whether TGF-ß1 can modulate the macrophage uptake of native or oxidized VLDL-REMs (oxVLDL-REMs). Incubation of J774A.1 macrophages with VLDL-REMs and oxVLDL-REMs compared with control cells increased cellular CE (13- and 21-fold, respectively) and TG mass (21-and 18-fold, respectively). Preincubation with TGF-ß1 before incubation with VLDL-REMs or oxVLDL-REMs significantly decreased CE (73% and 54%, respectively) and TG mass (42% and 41%, respectively). TGF-ß1 inhibited the activity and expression of 2 key components needed for VLDL-REM uptake: lipoprotein lipase and low density lipoprotein receptor. TGF-ß1 inhibited CE mass induced by oxVLDL-REMs in part by decreasing the expression of scavenger receptor type AI/II and CD36. Furthermore, TGF-ß1 enhanced cholesterol efflux through upregulation of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. Thus, TGF-ß1 inhibits macrophage foam cell formation induced by VLDL-REMs or oxVLDL-REMs, which suggests an antiatherogenic role for this cytokine.
Key Words: atherosclerosis • macrophages • transforming growth factor-ß1 • lipoproteins
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