In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 21, No. 12 ( 2001-12), p. 2011-2018
Abstract:
Transforming growth factor β1 (TGF-β1) is secreted by various cells, including macrophages, smooth muscle cells, and endothelial cells. TGF-β1 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-β1 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-β1 before incubation with VLDL-REMs or oxVLDL-REMs significantly decreased CE (73% and 54%, respectively) and TG mass (42% and 41%, respectively). TGF-β1 inhibited the activity and expression of 2 key components needed for VLDL-REM uptake: lipoprotein lipase and low density lipoprotein receptor. TGF-β1 inhibited CE mass induced by oxVLDL-REMs in part by decreasing the expression of scavenger receptor type AI/II and CD36. Furthermore, TGF-β1 enhanced cholesterol efflux through upregulation of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. Thus, TGF-β1 inhibits macrophage foam cell formation induced by VLDL-REMs or oxVLDL-REMs, which suggests an antiatherogenic role for this cytokine.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/hq1201.099426
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2001
detail.hit.zdb_id:
1494427-3
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