HDL inhibits saturated fatty acid mediated augmentation of innate immune responses in endothelial cells by a novel pathway

Wei Yang Zhang, Daniel A. Franco, Eric Schwartz, Karen D'Souza, Sheetal Karnick, Peter D. Reaven

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background and aims Peripheral insulin resistance is associated with several metabolic abnormalities, including elevated serum fatty acids that contribute to vascular injury and atherogenesis. Our goals were to examine whether saturated fatty acids can modify innate immune responses to subclinical concentrations of lipopolysaccharide (LPS) in endothelial cells, and to explore the underlying pathway and determine whether it is modified by high density lipoprotein (HDL) and other factors commonly altered in insulin resistance. Methods Physiologic concentrations of palmitic acid were added to human aortic endothelial cells with and without a variety of inhibitors or HDL and measures of cell inflammation and function assessed. Results Palmitic acid significantly amplified human aortic endothelial cell inflammatory responses to LPS. Similar results were obtained from lipolysis products of triglyceride rich lipoproteins. Metabolism of palmitic acid to ceramide and subsequent activation of PKC-ζ, MAPK and ATF3 appeared critical in amplifying LPS induced inflammation. The amplified response to palmitic acid/LPS was decreased by HDL, dose dependently, and this inhibition was dependent on activation of PI3K/AKT and reduction in ATF3. Conclusions These results indicate that endothelial cell innate immune responses are modified by metabolic abnormalities commonly present in insulin resistance and provide evidence for a novel mechanism by which HDL may reduce vascular inflammation.

Original languageEnglish (US)
Pages (from-to)83-96
Number of pages14
JournalAtherosclerosis
Volume259
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

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Keywords

  • ATF3
  • Cell signaling
  • HDL
  • Inflammation
  • MAP kinase
  • Saturated fatty acid

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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