Excessive intake of trans fatty acid accelerates atherosclerosis through promoting inflammation and oxidative stress in a mouse model of hyperlipidemia

Background: Epidemiological studies have demonstrated that trans fatty acids (TFAs) are a risk for coronary artery disease. However, the precise mechanism underlying the proatherogenic effect of TFA has not been completely elucidated. To obtain better understanding of the impact of TFA on vascular diseases, this study investigated the effect of TFA on oxidative stress using a mouse model of atherosclerosis. Methods: Low-density lipoprotein (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. Atherosclerotic lesion and oxidative stress in aortic wall were evaluated. In vitro experiments using smooth muscle cells were performed to corroborate in vivo findings. Results: The atherosclerotic lesion area was significantly larger in Trans group than that in control or Cis group. Lipoprotein fractionation was similar among groups, while plasma oxidized LDL level and superoxide production in the vessel wall were markedly increased in Trans group. Elaidic acids were accumulated in a variety of tissues including liver and adipose tissue, which was associated with the high level of inflammatory cytokines in these tissues and plasma. Aortic wall from Trans group showed augmented expression of reactive oxygen species and NAPDH oxidase (p22phox) in smooth muscle cells. In vitro experiments confirmed that elaidic acids upregulated expression of NADPH oxidase and inflammatory cytokines in cultured smooth muscle cells. Conclusion: Excessive intake of TFA contributes to the progression of atherosclerosis by evoking inflammation and oxidative stress in mice. (C) 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.