Palmitic Acid Increases Medial Calcification by Inducing Oxidative Stress
Palmitic Acid Increases Medial Calcification by Inducing Oxidative Stress
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DOI：
10.1159/000354235
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发表时间：
2013-01-01
影响因子：
1.7
通讯作者：
Moreau, Pierre
中科院分区：
文献类型：
--
作者：
Brodeur, Mathieu R.;Bouvet, Celine;Moreau, Pierre
背景：主动脉中膜钙化是一个细胞调节的过程，导致动脉硬化。尽管流行病学研究表明脂肪酸（FA）饱和度与动脉僵硬度之间存在关联，但没有证据表明饱和的FA可诱导动脉钙化。本研究探讨了棕榈酸（PA）诱导中膜钙化的能力以及参与这一过程的信号通路。方法：将大鼠主动脉节段和血管平滑肌细胞（VSMC）暴露于含PA的钙化培养基中。在体内，用华法林处理大鼠以诱导钙化，并喂食富含PA的饮食。结果：在体外和离体，棕榈酸盐增加钙化和ROS的产生。棕榈酸增加细胞外信号调节激酶（ERK 1/2）磷酸化和成骨基因表达。用夹竹桃素或siRNA抑制NADPH氧化酶可防止这些作用。ERK 1/2抑制减弱棕榈酸诱导的成骨基因表达和钙化的扩增。在体内，富含PA的饮食放大了中膜钙化和脉搏波速度（PWV）。这些作用是由ROS产生介导的，如伴随用夹竹桃麻素处理的大鼠中的钙化和PWV正常化的抑制所示。结论：棕榈酸酯诱导ROS的产生，导致ERK 1/2磷酸化，进而诱导VSMC向成骨细胞分化。(C)2013 S. Karger AG，巴塞尔
Background: Aortic medial calcification is a cellular-regulated process leading to arterial stiffness. Although epidemiological studies have suggested an association between the saturation of fatty acids (FA) and arterial stiffness, there is no evidence that saturated FA can induce arterial calcification. This study investigated the capacity of palmitic acid (PA) to induce medial calcification and the signaling pathway(s) implicated in this process. Methods: Rat aortic segments and vascular smooth muscle cells (VSMC) were exposed to calcification medium supplemented with PA. In vivo, rats were treated with warfarin to induce calcification and fed a PA-enriched diet. Results: In vitro and ex vivo, palmitate increases calcification and ROS production. Palmitate increases extracellular-signal-regulated kinase (ERK1/2) phosphorylation and osteogenic gene expression. Inhibition of NADPH oxidase with apocynin or an siRNA prevents these effects. ERK1/2 inhibition attenuates the amplification of osteogenic gene expression and calcification induced by palmitate. In vivo, a PA-enriched diet amplified medial calcification and pulse wave velocity (PWV). These effects are mediated by ROS production as indicated by the inhibition of calcification and PWV normalization in rats concomitantly treated with apocynin. Conclusion: ROS induction by palmitate leads to ERK1/2 phosphorylation and subsequently induces the osteogenic differentiation of VSMC. (C) 2013 S. Karger AG, Basel