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

McGrath, KCY; Li, XH; Puranik, R; Liong, EC; Tan, JTM; Dy, VM; Dibartolo, BA; Barter, PJ; Rye, KA; Heather, AK

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

McGrath, KCY

Li, XH Puranik, R Liong, EC Tan, JTM Dy, VM Dibartolo, BA Barter, PJ Rye, KA Heather, AK

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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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Field	Value	Language
dc.contributor.author	McGrath, KCY https://orcid.org/0000-0002-6244-3929	en_US
dc.contributor.author	Li, XH	en_US
dc.contributor.author	Puranik, R	en_US
dc.contributor.author	Liong, EC	en_US
dc.contributor.author	Tan, JTM	en_US
dc.contributor.author	Dy, VM	en_US
dc.contributor.author	Dibartolo, BA	en_US
dc.contributor.author	Barter, PJ	en_US
dc.contributor.author	Rye, KA	en_US
dc.contributor.author	Heather, AK	en_US
dc.date.issued	2009-06-01	en_US
dc.identifier.citation	Arteriosclerosis, Thrombosis, and Vascular Biology, 2009, 29 (6), pp. 877 - 882	en_US
dc.identifier.issn	1079-5642	en_US
dc.identifier.uri	http://hdl.handle.net/10453/17018
dc.description.abstract	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.	en_US
dc.relation.ispartof	Arteriosclerosis, Thrombosis, and Vascular Biology	en_US
dc.relation.isbasedon	10.1161/ATVBAHA.109.184663	en_US
dc.subject.classification	Cardiovascular System & Hematology	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Endothelial Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Rabbits	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Arteritis	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Oxidoreductases Acting on CH-CH Group Donors	en_US
dc.subject.mesh	Cholesterol, Dietary	en_US
dc.subject.mesh	Lipoproteins, HDL	en_US
dc.subject.mesh	Tumor Necrosis Factor-alpha	en_US
dc.subject.mesh	Apolipoprotein A-I	en_US
dc.subject.mesh	NF-kappa B	en_US
dc.subject.mesh	Vascular Cell Adhesion Molecule-1	en_US
dc.subject.mesh	Nerve Tissue Proteins	en_US
dc.subject.mesh	RNA, Small Interfering	en_US
dc.subject.mesh	Infusions, Intravenous	en_US
dc.subject.mesh	Gene Expression Profiling	en_US
dc.subject.mesh	Transfection	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	RNA Interference	en_US
dc.subject.mesh	I-kappa B Proteins	en_US
dc.subject.mesh	Atherosclerosis	en_US
dc.subject.mesh	I-kappa B Kinase	en_US
dc.subject.mesh	Promoter Regions, Genetic	en_US
dc.subject.mesh	NF-KappaB Inhibitor alpha	en_US
dc.title	Role of 3β-hydroxysteroid-Δ24 reductase in mediating antiinflammatory effects of high-density lipoproteins in endothelial cells	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.citation.volume	29	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1103 Clinical Sciences	en_US
dc.location.activity	ISI:000266242700016	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	29	en_US

Abstract:

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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http://hdl.handle.net/10453/17018