University of North Carolina Greensboro, Joint School of Nanoscience and Nanoengineering, Greensboro, NC, United States.
University of North Carolina Greensboro, Joint School of Nanoscience and Nanoengineering, Greensboro, NC, United States.
Nanomedicine. 2017 Aug;13(6):2037-2048. doi: 10.1016/j.nano.2017.04.013. Epub 2017 Apr 27.
The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology.Lipoprotein-induced generation of TNF-α, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to be mediated through the NF-κB pathway as FD reduced expression of NF-κB and atherosclerosis-associated genes. Compared to controls, FD dramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization.
单核细胞来源的巨噬细胞向富含脂质的泡沫细胞的转化是动脉粥样硬化疾病的一个炎症过程。先前的研究表明，富勒烯衍生物（FDs）具有抗炎作用。因此，研究假设 FD 可以抑制泡沫细胞形成的转化过程。富勒烯衍生物通过脂染色和形态学来抑制佛波醇肉豆蔻酸/氧化低密度脂蛋白诱导的巨噬细胞向泡沫细胞的分化。与未经处理的细胞相比，FD 处理的细胞中脂蛋白诱导的 TNF-α产生、C5a 诱导的 MC 活化、ICAM-1 驱动的黏附和 CD36 表达明显受到抑制。抑制作用似乎是通过 NF-κB 途径介导的，因为 FD 降低了 NF-κB 和动脉粥样硬化相关基因的表达。与对照组相比，FD 可显著抑制载脂蛋白 E 基因敲除小鼠动脉中的斑块形成。因此，FD 可能是一种通过抑制泡沫细胞形成和 MC 稳定来预防动脉粥样硬化病变的未被识别的治疗方法。
