Monguchi Tomoko, Hara Tetsuya, Hasokawa Minoru, Nakajima Hideto, Mori Kenta, Toh Ryuji, Irino Yasuhiro, Ishida Tatsuro, Hirata Ken-Ichi, Shinohara Masakazu
Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
J Cardiol. 2017 Aug;70(2):121-127. doi: 10.1016/j.jjcc.2016.12.012. Epub 2017 Feb 21.
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.
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.
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.
Excessive intake of TFA contributes to the progression of atherosclerosis by evoking inflammation and oxidative stress in mice.
流行病学研究表明，反式脂肪酸（TFAs）是冠状动脉疾病的一个风险因素。然而，TFA促动脉粥样硬化作用的确切机制尚未完全阐明。为了更好地了解TFA对血管疾病的影响，本研究使用动脉粥样硬化小鼠模型研究了TFA对氧化应激的影响。
给低密度脂蛋白（LDL）受体敲除小鼠喂食含0.5%胆固醇的饮食（对照组）、0.5%胆固醇+5%反油酸（反式组）和0.5%胆固醇+5%油酸（顺式组），持续8周。评估主动脉壁的动脉粥样硬化病变和氧化应激。进行平滑肌细胞的体外实验以证实体内研究结果。
反式组的动脉粥样硬化病变面积明显大于对照组或顺式组。各组间脂蛋白分级相似，而反式组的血浆氧化LDL水平和血管壁中超氧化物生成明显增加。反油酸在包括肝脏和脂肪组织在内的多种组织中蓄积，这与这些组织和血浆中高水平的炎性细胞因子有关。反式组的主动脉壁平滑肌细胞中活性氧和NAPDH氧化酶（p22phox）的表达增加。体外实验证实，反油酸上调了培养的平滑肌细胞中NADPH氧化酶和炎性细胞因子的表达。
过量摄入TFA通过引发小鼠炎症和氧化应激促进动脉粥样硬化进展。
