Role of 3β-hydroxysteroid-Δ24 reductase in mediating antiinflammatory effects of high-density lipoproteins in endothelial cells

Publication Type:
Journal Article
Citation:
Arteriosclerosis, Thrombosis, and Vascular Biology, 2009, 29 (6), pp. 877 - 882
Issue Date:
2009-06-01
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OBJECTIVE-: The purpose of this study was to investigate the ability of high-density lipoproteins (HDLs) to upregulate genes with the potential to protect against inflammation in endothelial cells. METHODS AND RESULTS-: Human coronary artery endothelial cells (HCAECs) were exposed to reconstituted HDLs (rHDLs) for 16 hours before being activated with tumor necrosis factor-α (TNF-α) for 5 hours. rHDLs decreased vascular cell adhesion molecule-1 (VCAM-1) promoter activity by 75% (P<0.05), via the nuclear factor-kappa B (NF-κB) binding site. rHDLs suppressed the canonical NF-κB pathway and decreased many NF-κB target genes. Suppression of NF-κB and VCAM-1 expression by rHDLs or native HDLs was dependent on an increase in 3β-hydroxysteroid-Δ24 reductase (DHCR24) levels (P<0.05). The effect of HDLs on DHCR24 is dependent on SR-BI but not ABCAI or ABCGI. Silencing DHCR24 expression increased NF-κB (1.2-fold, P<0.05), VCAM-1 (30-fold, P<0.05), and NF-κB p50 (4-fold, P<0.05) and p65 subunits (150-fold, P<0.05). TNF-α activation of siDHCR24-treated cells increased expression of VCAM-1 (550-fold, P<0.001) and NF-κB (9-fold, P<0.001) that could no longer be suppressed by rHDLs. CONCLUSIONS-: Results suggest that antiinflammatory effects of rHDLs are mediated partly through an upregulation of DHCR24. These findings raise the possibility of considering DHCR24 as a target for therapeutic modulation. © 2009 American Heart Association, Inc.
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