Oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation plays an important role in the development of cardiovascular diseases. G protein-coupled receptors (GPCR) are gaining traction as potential treatment targets due to their roles in mediating a wide range of physiological processes. GPR120 is a recently identified omega-3 fatty acid receptor. We hypothesized that agonism of GPR120 might attenuate ox-LDL-induced endothelial dysfunction. In the present study, we tested the effects of two GPR120 agonists-GW9508 and TUG-891-in mitigating endothelial insult induced by ox-LDL in human aortic endothelial cells (HAECs). Real-time PCR, western blot, and ELISA analyses were used in our experiments. Our findings demonstrate that GPR120 is downregulated by exposure to ox-LDL, suggesting a role for GPR120 in mediating ox-LDL insult. Furthermore, we found that agonism of GPR120 could suppress oxidative stress and inflammation by inhibiting the production of reactive oxygen species and the expression of proinflammatory cytokines. Importantly, we show that agonism of GPR120 prevents the attachment of monocytes to endothelial cells by suppressing the expression of VCAM-1 and E-selectin. Finally, we show that agonism of GPR120 exerts a remarkable atheroprotective effect by elevating the expression level of Krüppel-like factor 2 (KLF2). Together, our results demonstrate a potential role for specific agonism of GPR120 in the prevention of endothelial damages induced by ox-LDL.

中文翻译：

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GPR120 的激动作用可防止 ox-LDL 诱导的单核细胞与内皮细胞的附着。

氧化低密度脂蛋白（ox-LDL）诱导的内皮炎症在心血管疾病的发展中起着重要作用。G 蛋白偶联受体 (GPCR) 由于其在介导广泛的生理过程中的作用而成为潜在的治疗靶点。GPR120 是最近发现的 omega-3 脂肪酸受体。我们假设 GPR120 的激动作用可能会减轻 ox-LDL 诱导的内皮功能障碍。在本研究中，我们测试了两种 GPR120 激动剂 GW9508 和 TUG-891 在减轻人主动脉内皮细胞 (HAEC) 中 ox-LDL 诱导的内皮损伤方面的作用。我们的实验中使用了实时 PCR、蛋白质印迹和 ELISA 分析。我们的研究结果表明，GPR120 通过暴露于 ox-LDL 而下调，表明 GPR120 在介导 ox-LDL 损伤中发挥作用。此外，我们发现 GPR120 的激动作用可以通过抑制活性氧的产生和促炎细胞因子的表达来抑制氧化应激和炎症。重要的是，我们发现 GPR120 的激动作用通过抑制 VCAM-1 和 E-选择素的表达来阻止单核细胞与内皮细胞的附着。最后，我们发现 GPR120 的激动剂通过提高 Krüppel 样因子 2 (KLF2) 的表达水平发挥显着的动脉粥样硬化作用。总之，我们的结果证明了 GPR120 的特异性激动在预防 ox-LDL 诱导的内皮损伤中具有潜在作用。