TNF-α induces acyl-CoA synthetase 3 to promote lipid droplet formation in human endothelial cells.

Abstract:

:Chronic inflammation contributes to cardiovascular disease. Increased levels of the inflammatory cytokine, TNF-α, are often present in conditions associated with cardiovascular disease risk, and TNF-α induces a number of pro-atherogenic effects in macrovascular endothelial cells, including expression of adhesion molecules and chemokines, and lipoprotein uptake and transcytosis to the subendothelial tissue. However, little is known about the roles of acyl-CoA synthetases (ACSLs), enzymes that esterify free fatty acids into their acyl-CoA derivatives, or about the effects of TNF-α on ACSLs in endothelial cells. Therefore, we investigated the effects of TNF-α on ACSLs and downstream lipids in cultured human coronary artery endothelial cells and human umbilical vein endothelial cells. We demonstrated that TNF-α induces ACSL1, ACSL3, and ACSL5, but not ACSL4, in both cell types. TNF-α also increased oleoyl-CoA levels, consistent with the increased ACSL3 expression. RNA-sequencing demonstrated that knockdown of ACSL3 had no marked effects on the TNF-α transcriptome. Instead, ACSL3 was required for TNF-α-induced lipid droplet formation in cells exposed to oleic acid. These results demonstrate that increased acyl-CoA synthesis as a result of ACSL3 induction is part of the TNF-α response in human macrovascular endothelial cells.

journal_name

J Lipid Res

authors

Jung HS,Shimizu-Albergine M,Shen X,Kramer F,Shao D,Vivekanandan-Giri A,Pennathur S,Tian R,Kanter JE,Bornfeldt KE

doi

10.1194/jlr.RA119000256

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

33-44

issue

1

eissn

0022-2275

issn

1539-7262

pii

jlr.RA119000256

journal_volume

61

pub_type

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