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Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1364-9. Epub 2005 May 26.

Antiinflammatory effects of tetradecylthioacetic acid involve both peroxisome proliferator-activated receptor alpha-dependent and -independent pathways.

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1
Institute of Medicine, Section of Medical Biochemistry, University of Bergen, Haukeland University Hospital, Bergen, Norway. endre.dyroy@med.uib.no

Abstract

OBJECTIVE:

Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs). Human endothelial cells express PPARs. We hypothesized that TTA could modulate endothelial cell activation at least partly through PPAR-related mechanisms.

METHODS AND RESULTS:

We explored this hypothesis by different experimental approaches involving both in vitro studies in human endothelial cells (HUVECs) and in vivo studies in humans and PPAR-alpha-/- mice. Our main findings were as follows: (1) TTA suppressed the tumor necrosis factor alpha-induced expression of vascular cell adhesion molecule 1 (VCAM-1) and interleukin 8 (IL-8) in HUVECs. (2) No TTA-mediated attenuation of VCAM-1 and chemokine expression was seen in the liver of PPAR-alpha-/- mice. (3) Whereas TTA markedly enhanced PPAR-alpha-target genes in the liver of wild-type, but not of PPAR-alpha-/-, mice, no such effect on PPAR-alpha-target genes was seen in HUVECs. (4) The relevance of our findings to human disease was suggested by a TTA-mediated downregulation of serum levels of soluble VCAM-1 and IL-8 in psoriasis patients.

CONCLUSIONS:

We show that TTA has the ability to attenuate tumor necrosis factor alpha-mediated endothelial cell activation, further supporting antiinflammatory effects of this fatty acid, possibly involving both PPAR-alpha-dependent and -independent pathways.

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