Endothelial Acyl-CoA synthetase 1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment

Xin Li, Oscar Gonzalez, Xia Shen, Shelley Barnhart, Farah Kramer, Jenny E. Kanter, Anuradha Vivekanandan-Giri, Kyoichiro Tsuchiya, Priya Handa, Subramaniam Pennathur, Francis Kim, Rosalind A. Coleman, Jean E. Schaffer, Karin E. Bornfeldt

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Objective-: Saturated fatty acids, such as palmitic and stearic acid, cause detrimental effects in endothelial cells and have been suggested to contribute to macrophage accumulation in adipose tissue and the vascular wall, in states of obesity and insulin resistance. Long-chain fatty acids are believed to require conversion into acyl-CoA derivatives to exert most of their detrimental effects, a reaction catalyzed by acyl-CoA synthetases (ACSLs). The Objective of this study was to investigate the role of ACSL1, an ACSL isoform previously shown to mediate inflammatory effects in myeloid cells, in regulating endothelial cell responses to a saturated fatty acid-rich environment in vitro and in vivo. METHODS AND RESULTS-: Saturated fatty acids caused increased inflammatory activation, endoplasmic reticulum stress, and apoptosis in mouse microvascular endothelial cells. Forced ACSL1 overexpression exacerbated the effects of saturated fatty acids on apoptosis and endoplasmic reticulum stress. However, endothelial ACSL1 deficiency did not protect against the effects of saturated fatty acids in vitro, nor did it protect insulin-resistant mice fed a saturated fatty acid-rich diet from macrophage adipose tissue accumulation or increased aortic adhesion molecule expression. CONCLUSION-: Endothelial ACSL1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.

Original languageEnglish
Pages (from-to)232-240
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume33
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • acyl-CoA synthetase
  • apoptosis
  • endothelium
  • inflammation

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    Li, X., Gonzalez, O., Shen, X., Barnhart, S., Kramer, F., Kanter, J. E., Vivekanandan-Giri, A., Tsuchiya, K., Handa, P., Pennathur, S., Kim, F., Coleman, R. A., Schaffer, J. E., & Bornfeldt, K. E. (2013). Endothelial Acyl-CoA synthetase 1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment. Arteriosclerosis, thrombosis, and vascular biology, 33(2), 232-240. https://doi.org/10.1161/ATVBAHA.112.252239