<br>Feprazone 通过减轻 TLR4/MyD88/NF-κB 通路的激活来预防游离脂肪酸（FFA）诱导的内皮炎症,ACS Omega

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Feprazone 通过减轻 TLR4/MyD88/NF-κB 通路的激活来预防游离脂肪酸（FFA）诱导的内皮炎症
ACS Omega ( IF 3.7 ) Pub Date : 2021-02-09 , DOI: 10.1021/acsomega.0c05826
Min Song ₁ , Liukun Meng ₁ , Xiaoxi Liu ₁ , Yan Yang ₁

Affiliation

游离脂肪酸（FFA）诱导的内皮功能障碍水平升高在动脉粥样硬化的发生和发展中起着重要作用。Feprazone 是一种非甾体抗炎化合物。然而，非泼酮对 FFA 诱导的内皮功能障碍的有益影响以前没有报道。在目前的研究中，我们发现 feprazone 治疗通过恢复细胞活力和减少乳酸脱氢酶（LDH）的释放来改善 FFA 诱导的人主动脉内皮细胞（HAECs）细胞死亡。重要的是，我们发现 feprazone 治疗通过减少线粒体活性氧（ROS）的产生来改善 FFA 诱导的氧化应激。此外，feprazone 阻止了 FFA 诱导的促炎细胞因子和趋化因子的表达和分泌，例如趋化因子配体 5 （CCL5）、白细胞介素-6 （IL-6）和白细胞介素-8 （IL-8）。我们还发现 feprazone 降低了基质金属蛋白酶-2 （MMP-2）和基质金属蛋白酶-9 （MMP-9）的表达。有趣的是，我们发现 feprazone 降低了细胞粘附分子的表达，例如血管细胞粘附分子-1 （VCAM-1）和细胞间细胞粘附分子-1 （ICAM-1）。我们的结果还表明，feprazone 阻止了 FFA 诱导的 toll 样受体 4 （TLR4） / 髓样分化因子 88 （MyD88） / 核因子 kappa-B （NF-κB）信号通路的激活。这些发现表明，feprazone 可能通过改善内皮功能作为治疗动脉粥样硬化的潜在药物。

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Feprazone Prevents Free Fatty Acid (FFA)-Induced Endothelial Inflammation by Mitigating the Activation of the TLR4/MyD88/NF-κB Pathway

Increased levels of free fatty acid (FFA)-induced endothelial dysfunction play an important role in the initiation and development of atherosclerosis. Feprazone is a nonsteroidal anti-inflammatory compound. However, the beneficial effects of feprazone on FFA-induced endothelial dysfunction have not been reported before. In the current study, we found that treatment with feprazone ameliorated FFA-induced cell death of human aortic endothelial cells (HAECs) by restoring cell viability and reducing the release of lactate dehydrogenase (LDH). Importantly, we found that treatment with feprazone ameliorated FFA-induced oxidative stress by reducing the production of mitochondrial reactive oxygen species (ROS). In addition, feprazone prevented FFA-induced expression and secretion of proinflammatory cytokines and chemokines, such as chemokine ligand 5 (CCL5), interleukin-6 (IL-6), and interleukin-8 (IL-8). We also found that feprazone decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Interestingly, we found that feprazone reduced the expression of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). Our results also demonstrate that feprazone prevented FFA-induced activation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway. These findings suggest that feprazone might serve as a potential agent for the treatment of atherosclerosis by improving the endothelial function.

更新日期：2021-02-23

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