Abstract：
Vascular endothelial cell functions affect lower extremity arteriosclerosis obliterans (LEASO), while alpha-2-macroglobulin (A2M) and CCCTC-binding factor (CTCF) are closely related to the function of such cells. This paper aims to identify the influences of CTCF on vascular endothelial cells in LEASO by regulating A2M. A rat model of LEASO was established to measure intima-media ratio, blood lipid, and inflammatory factor levels. By constructing LEASO cell models, cell viability and apoptosis were assayed, while autophagy-related proteins, CTCF and A2M levels in femoral artery tissues and HUVECs were determined. The transcriptional regulation of CTCF on A2M was verified. In LEASO rat models, femoral artery lumen was narrowed and endothelial cells were disordered; levels of total cholesterol, IL-1, and TNF-α enhanced, and HDL-C decreased, with strong expression of A2M and low expression of CTCF. The viability of ox-LDL-treated HUVECs was decreased, together with higher apoptosis, lower LC3II/I expression, and higher p62 expression, which were reversed by sh-A2M transfection. Overexpression of CTCF inhibited A2M transcription, promoted the viability and autophagy of HUVECs, and decreased apoptosis. Collectively, CTCF improves the function of vascular endothelial cells in LEASO by inhibiting A2M transcription.
摘要：
血管内皮细胞功能影响下肢动脉硬化闭塞症（LEASO），而α-2-巨球蛋白（A2M）和CCCTC结合因子（CTCF）与此类细胞的功能密切相关。本文旨在研究CTCF通过调节A2M对LEASO血管内皮细胞的影响。建立LEASO大鼠模型，测量内膜-中膜比，血脂，和炎症因子水平。通过构建LEASO细胞模型，测定细胞活力和细胞凋亡，而自噬相关蛋白，测定股动脉组织和HUVECs中的CTCF和A2M水平。证实了CTCF对A2M的转录调控。在LEASO大鼠模型中,股动脉管腔变窄，内皮细胞紊乱；总胆固醇水平，IL-1和TNF-α增强，HDL-C下降，A2M强表达，CTCF低表达。ox-LDL处理的HUVECs的活力降低,伴随着更高的细胞凋亡，较低的LC3II/I表达，和更高的p62表达，通过sh-A2M转染逆转。CTCF过表达抑制A2M转录,促进HUVECs的活力和自噬，细胞凋亡减少。总的来说，CTCF通过抑制A2M转录改善LEASO中血管内皮细胞的功能。
