In atherosclerosis, macrophage-derived foam cell formation is considered to be a hallmark of the pathological process; this occurs via the uptake of modified lipoproteins. In the present study, we aim to determine the role of transaldolase in foam cell formation and atherogenesis and reveal the mechanisms underlying its role. Bone marrow-derived macrophages (BMDMs) isolated from mice successfully form foam cells after treatment with oxidized low-density lipoprotein (80 μg/mL). Elevated transaldolase levels in the foam cell model are assessed by quantitative polymerase chain reaction and western blot analysis. Transaldolase overexpression and knockdown in BMDMs are achieved via plasmid transfection and small interfering RNA technology, respectively. We find that transaldolase overexpression effectively attenuates, whereas transaldolase knockdown accelerates, macrophage-derived foam cell formation through the inhibition or activation of cholesterol uptake mediated by the scavenger receptor cluster of differentiation 36 (CD36) in a p38 mitogen-activated protein kinase (MAPK) signaling-dependent manner. Transaldolase-mediated glutathione (GSH) homeostasis is identified as the upstream regulator of p38 MAPK-mediated CD36-dependent cholesterol uptake in BMDMs. Transaldolase upregulates GSH production, thereby suppressing p38 activity and reducing the CD36 level, ultimately preventing foam cell formation and atherosclerosis. Thus, our findings indicate that the transaldolase-GSH-p38-CD36 axis may represent a promising therapeutic target for atherosclerosis.

中文翻译：

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转醛醇酶通过调节谷胱甘肽-p38 信号传导抑制 CD36 表达，对巨噬细胞泡沫细胞形成发挥保护作用。

在动脉粥样硬化中，巨噬细胞衍生的泡沫细胞形成被认为是病理过程的标志。这是通过吸收修饰的脂蛋白而发生的。在本研究中，我们的目的是确定转醛醇酶在泡沫细胞形成和动脉粥样硬化形成中的作用，并揭示其作用的机制。从小鼠体内分离的骨髓源性巨噬细胞 (BMDM) 在用氧化低密度脂蛋白 (80 μg/mL) 处理后成功形成泡沫细胞。通过定量聚合酶链反应和蛋白质印迹分析评估泡沫细胞模型中升高的转醛醇酶水平。BMDM 中转醛醇酶的过表达和敲低分别通过质粒转染和小干扰 RNA 技术实现。我们发现，转醛醇酶过表达可有效减弱巨噬细胞衍生的泡沫细胞形成，而转醛醇酶敲低可通过抑制或激活 p38 丝裂原激活蛋白激酶 (MAPK) 中的分化清道夫受体簇 36 (CD36) 介导的胆固醇摄取来加速巨噬细胞衍生的泡沫细胞形成。信号依赖方式。转醛醇酶介导的谷胱甘肽 (GSH) 稳态被确定为 BMDM 中 p38 MAPK 介导的 CD36 依赖性胆固醇摄取的上游调节因子。转醛醇酶上调 GSH 的产生，从而抑制 p38 活性并降低 CD36 水平，最终防止泡沫细胞形成和动脉粥样硬化。因此，我们的研究结果表明转醛醇酶-GSH-p38-CD36轴可能代表动脉粥样硬化的有希望的治疗靶点。