Wu Di, Liu Juntian, Pang Xiaoming, Wang Shuyue, Zhao Jingjing, Zhang Xiaolu, Feng Liuxin
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, P.R. China.
Int J Mol Med. 2014 Dec;34(6):1706-12. doi: 10.3892/ijmm.2014.1942. Epub 2014 Sep 22.
Atherosclerosis is a chronic inflammatory disease in the vessel, and inflammatory cytokines play an important role in the inflammatory process of atherosclerosis. A high level of free fatty acids (FFAs) produced in lipid metabolism disorders are known to participate in the formation of atherosclerosis through multiple bioactivities. As the main saturated fatty acid in FFAs, palmitic acid stimulates the expression of inflammatory cytokines in macrophages. However, it is unclear whether palmitic acid exerts a pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of palmitic acid on the expression of C-reactive protein (CRP), tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in VSMCs. Rat VSMCs were cultured, and palmitic acid was used as a stimulant for CRP, TNF-α and iNOS expression. mRNA expression was assayed with reverse transcription-polymerase chain reaction, and protein expression was detected with western blot analysis and immunocytochemistry. The results showed that palmitic acid significantly stimulated mRNA and protein expression of CRP, TNF-α and iNOS in VSMCs in time- and concentration-dependent manners, and therefore, palmitic acid is able to exert a pro-inflammatory effect on VSMCs via stimulating CRP, TNF-α and iNOS expression. The findings provide a novel explanation for the direct pro-inflammatory and atherogenic effects of palmitic acid, and for the association with metabolic syndrome, such as type 2 diabetes mellitus, obesity and atherosclerosis. Therefore, the intervention with anti-inflammatory agents may effectively delay the formation and progression of atherosclerosis in patients with metabolic syndrome.
动脉粥样硬化是一种血管慢性炎症性疾病，炎症细胞因子在动脉粥样硬化的炎症过程中起重要作用。已知脂质代谢紊乱产生的高水平游离脂肪酸（FFA）通过多种生物活性参与动脉粥样硬化的形成。作为FFA中的主要饱和脂肪酸，棕榈酸刺激巨噬细胞中炎症细胞因子的表达。然而，尚不清楚棕榈酸是否对血管平滑肌细胞（VSMC）产生促炎作用。本研究的目的是观察棕榈酸对VSMC中C反应蛋白（CRP）、肿瘤坏死因子α（TNF-α）和诱导型一氧化氮合酶（iNOS）表达的影响。培养大鼠VSMC，并用棕榈酸作为CRP、TNF-α和iNOS表达的刺激剂。用逆转录-聚合酶链反应检测mRNA表达，用蛋白质印迹分析和免疫细胞化学检测蛋白质表达。结果表明，棕榈酸以时间和浓度依赖性方式显著刺激VSMC中CRP、TNF-α和iNOS的mRNA和蛋白质表达，因此，棕榈酸能够通过刺激CRP、TNF-α和iNOS表达对VSMC发挥促炎作用。这些发现为棕榈酸的直接促炎和致动脉粥样硬化作用以及与代谢综合征（如2型糖尿病、肥胖症和动脉粥样硬化）的关联提供了新的解释。因此，用抗炎药物进行干预可能有效地延缓代谢综合征患者动脉粥样硬化的形成和进展。
