Abstract 14652: Trans Fatty Acids Induce Systemic Inflammation and Atherosclerosis Through Toll-Like Receptor-Mediated Pathway in LDL Receptor Knockout Mice
Background: Epidemiological studies have demonstrated that trans fatty acids (TFA) are a risk of coronary artery disease. However, the precise mechanism underlying the proatherogenic effect of TFA has not been completely elucidated.This study was undertaken to investigate the effect of TFA on arteriosclerosis using a mouse model of atherosclerosis.
Methods and Results: LDL receptor knockout mice were fed with diet containing 0.5% cholesterol (control), 0.5% cholesterol + 5% elaidic acids (Trans group), and 0.5% cholesterol + 5% oleic acids (Cis group) for 8 weeks. The atherosclerotic lesion area was significant larger in Trans group than that in control or Cis group. Plasma lipid profile was similar in these three groups. However, plasma levels of oxidized LDL were markedly increased in Trans group, and isolated LDL fraction after TFA treatment was susceptible to oxidation. Furthermore, gas chromatography/mass spectrometry analysis revealed that fatty acid elongation reaction was attenuated in the Trans group, implying the delayed catabolism of fatty acids. Levels of inflammatory cytokines such as TNFα and IL-1β in plasma and aorta were significantly higher in the Trans group than those in control or Cis group. In Trans group, elaidic acids were accumulated in a variety of tissues including liver and adipose tissue, and evoked inflammation in these tissues. Cell culture experiments revealed that TFA upregulated a variety of pro-atherogenic and pro-thrombogenic molecules in vascular endothelial cells by activation of the toll-like receptor (TLR) 2/4, mitogen-activated protein kinases, and NFkB pathway.
Conclusion: TFA evoke systemic inflammation and promote arteriosclerosis by deteriorating atheroprotective phenotype of vascular endothelial cells, promoting of LDL oxidation, and inhibiting fatty acid catabolism.These effects are mediated through TLR-dependent mechanism.
- © 2013 by American Heart Association, Inc.