Brodeur Mathieu R, Bouvet Céline, Barrette Mathieu, Moreau Pierre
Laboratoire de Pharmacologie Vasculaire, Faculté de Pharmacie, Université de Montréal, Montréal, Qué., Canada.
J Vasc Res. 2013;50(5):430-41. doi: 10.1159/000354235. Epub 2013 Sep 27.
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.
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.
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.
ROS induction by palmitate leads to ERK1/2 phosphorylation and subsequently induces the osteogenic differentiation of VSMC. © 2013 S. Karger AG, Basel.
主动脉中层钙化是一个细胞调控过程，可导致动脉僵硬。尽管流行病学研究表明脂肪酸（FA）饱和度与动脉僵硬之间存在关联，但尚无证据表明饱和FA可诱导动脉钙化。本研究调查了棕榈酸（PA）诱导中层钙化的能力以及该过程中涉及的信号通路。
将大鼠主动脉段和血管平滑肌细胞（VSMC）暴露于添加了PA的钙化培养基中。在体内，用华法林处理大鼠以诱导钙化，并给予富含PA的饮食。
在体外和离体实验中，棕榈酸盐增加钙化和活性氧（ROS）生成。棕榈酸盐增加细胞外信号调节激酶（ERK1/2）磷酸化和成骨基因表达。用夹竹桃麻素或小干扰RNA抑制NADPH氧化酶可阻止这些效应。抑制ERK1/2可减弱棕榈酸盐诱导的成骨基因表达放大和钙化。在体内，富含PA的饮食会加剧中层钙化和脉搏波速度（PWV）。夹竹桃麻素同时处理的大鼠中钙化受到抑制且PWV恢复正常，这表明这些效应是由ROS生成介导的。
棕榈酸盐诱导的ROS导致ERK1/2磷酸化，随后诱导VSMC的成骨分化。© 2013 S. Karger AG，巴塞尔。
