Cholesterol attenuates linoleic acid-induced endothelial cell activation

Purushothaman Meerarani, Eric J. Smart, Michal Toborek, Gilbert A. Boissonneault, Bernhard Hennig

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Vascular endothelial cell activation and dysfunction are critical early events in atherosclerosis. Even though very low or high levels of cholesterol can compromise cellular functions, cholesterol is a critical membrane component and may protect the vascular endothelium from oxidative stress and polyunsaturated fatty acid-mediated inflammatory responses. We have previously shown that the parent omega-6 fatty acid linoleic acid can markedly activate vascular endothelial cells. We now propose that membrane cholesterol can modify and inhibit linoleic acid-mediated endothelial cell dysfunction. To test this hypothesis, pulmonary artery endothelial cells were incubated with cholesterol (0 to 100 μmol/L) for 24 hours and then treated with 90 μmol/L of linoleic acid (18:2n-6) for 6 to 24 hours. In control cells, treatment with linoleic acid reduced intracellular glutathione levels and induced the DNA binding activity of nuclear factor-κB (NF-κB) leading to the upregulation of interleukin-6 (IL-6). In addition, the expression of endothelial nitric oxide synthase (eNOS) was altered, with linoleic acid increasing eNOS activity. In contrast, enrichment with cholesterol enhanced glutathione levels and reduced the linoleic acid-induced activation of NF-κBand the production of IL-6. Prior exposure to 50 μmol/L cholesterol also prevented the fatty acid-induced increase in eNOS activation. Cholesterol loading activated peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that can decrease inflammatory responses. Furthermore, the PPAR-γ agonist thiazolidinedione markedly downregulated the NF-κB activation mediated by linoleic acid. Our data suggest that signaling pathways linked to endothelial cell activation by prooxidant and proinflammatory insults may be influenced by cellular cholesterol levels.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalMetabolism: clinical and experimental
Volume52
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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