The present study was aimed at investigating the detailed functions of atorvastatin, a lipid-lowering agent, in the pathogenesis of coronary slow flow (CSF), a clinical disease characterized by delayed angiographic coronary opacity without obstructive coronary disease. In the present study, we successfully identified isolated endothelial progenitor cells (EPCs) from the peripheral blood of patients with CSF. Their VEGFA protein levels were determined using immunoblotting analyses. We determined cell viability using MTT assays, cell migration capacity using Transwell assays, and the angiogenic capacity using a tube formation assay. The target association between miR-221 and VEGFA was validated with a luciferase reporter assay. Atorvastatin treatment increased EPC VEGFA protein levels, proliferation, migration, and angiogenesis. miR-221 expression was downregulated after atorvastatin treatment; miR-221 overexpression exerted an opposing effect to atorvastatin treatment on VEGFA protein, EPC proliferation, migration, and angiogenesis. The protective effects of atorvastatin treatment on VEGFA protein and EPCs could be significantly suppressed by miR-221 overexpression. miR-221 directly bound the VEGFA 3'UTR to inhibit its expression. In conclusion, atorvastatin improves the cell proliferation, migration, and angiogenesis of EPCs via the miR-221/VEGFA axis. Thus, atorvastatin could be a potent agent against CSF, pending further in vivo and clinical investigations.

中文翻译：

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阿托伐他汀通过miR-221 / VEGFA轴改善内皮祖细胞中的细胞增殖和迁移。

本研究旨在研究阿托伐他汀（一种降脂药）在冠状动脉缓慢血流（CSF）的发病机理中的详细功能。冠状动脉缓慢血流（CSF）是一种临床疾病，其特征在于延迟性血管造影性冠状动脉混浊而不引起阻塞性冠心病。在本研究中，我们成功地从脑脊液患者的外周血中鉴定出分离的内皮祖细胞（EPC）。使用免疫印迹分析确定其VEGFA蛋白水平。我们使用MTT分析确定细胞活力，使用Transwell分析确定细胞迁移能力，并使用管形成分析确定血管生成能力。miR-221和VEGFA之间的靶点关联已通过萤光素酶报告基因分析得以验证。阿托伐他汀治疗可增加EPC VEGFA蛋白水平，增殖，迁移和血管生成。阿托伐他汀治疗后miR-221表达下调；miR-221过表达对阿托伐他汀治疗的VEGFA蛋白，EPC增殖，迁移和血管生成具有相反的作用。miR-221过表达可显着抑制阿托伐他汀治疗对VEGFA蛋白和EPC的保护作用。miR-221直接结合VEGFA 3'UTR以抑制其表达。总之，阿托伐他汀可通过miR-221 / VEGFA轴改善EPC的细胞增殖，迁移和血管生成。因此，阿托伐他汀可能是对抗脑脊液的有效药物，有待进一步的体内和临床研究。miR-221过表达可显着抑制阿托伐他汀对VEGFA蛋白和EPC的保护作用。miR-221直接结合VEGFA 3'UTR以抑制其表达。总之，阿托伐他汀可通过miR-221 / VEGFA轴改善EPC的细胞增殖，迁移和血管生成。因此，阿托伐他汀可能是对抗脑脊液的有效药物，有待进一步的体内和临床研究。miR-221过表达可显着抑制阿托伐他汀治疗对VEGFA蛋白和EPC的保护作用。miR-221直接结合VEGFA 3'UTR以抑制其表达。总之，阿托伐他汀可通过miR-221 / VEGFA轴改善EPC的细胞增殖，迁移和血管生成。因此，阿托伐他汀可能是对抗脑脊液的有效药物，有待进一步的体内和临床研究。