Endothelial cells play essential roles in angiogenesis. Heat shock protein A12B (HSPA12B), a novel member of the multigene Hsp70 family, expresses specifically in endothelial cells. Alpha-lipoic acid (LA) has been used for the treatment of human diabetic complications for more than 20 years. However, little is known whether LA impacts endothelial proliferation and migration. To address these questions, primary human umbilical vein endothelial cells (HUVECs) were isolated and treated with LA. We found that LA reduced viable HUVECs but not caused LDH leakage and nuclear condensation, suggesting an inhibitory effect of LA on HUVEC proliferation. We also noticed that LA impeded wound closure of HUVEC monolayers. The expressions of C-Myc, VEGF, and eNOS and phosphorylation of focal adhesion kinase were reduced by LA. Moreover, LA decreased the expression of heat shock protein A12B (HSPA12B). Notably, overexpression of HSPA12B in endothelial cells prevented the LA-induced loss of VEGF. More importantly, HSPA12B overexpression attenuated the LA-induced inhibition of endothelial proliferation and migration. Collectively, the results demonstrated that LA inhibited proliferative and migratory abilities in human vascular endothelial cells through the downregulation of the HSPA12B/VEGF signaling axis. The data suggest that besides the treatment in diabetic complications, LA might represent a viable therapeutic potential for human diseases that involve high angiogenic activities such as cancers.

中文翻译：

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α-硫辛酸通过下调HSPA12B / VEGF信号转导轴来抑制人血管内皮细胞的增殖和迁移。

内皮细胞在血管生成中起重要作用。热休克蛋白A12B（HSPA12B）是多基因Hsp70家族的新成员，在内皮细胞中特异性表达。α-硫辛酸（LA）已用于治疗人类糖尿病并发症超过20年。但是，关于LA是否会影响内皮细胞的增殖和迁移尚知之甚少。为了解决这些问题，分离了原代人脐静脉内皮细胞（HUVEC）并用LA治疗。我们发现洛杉矶减少了可行的HUVEC，但没有引起LDH泄漏和核凝聚，表明LA对HUVEC增殖具有抑制作用。我们还注意到，LA阻止了HUVEC单层的伤口闭合。LA降低了C-Myc，VEGF和eNOS的表达以及粘着斑激酶的磷酸化。此外，LA降低了热休克蛋白A12B（HSPA12B）的表达。值得注意的是，内皮细胞中HSPA12B的过度表达阻止了LA诱导的VEGF的丢失。更重要的是，HSPA12B的过表达减弱了LA诱导的内皮细胞增殖和迁移的抑制作用。总体而言，结果表明LA通过下调HSPA12B / VEGF信号轴来抑制人血管内皮细胞的增殖和迁移能力。数据表明，除糖尿病并发症的治疗外，LA还可能代表对涉及血管生成活性高的人类疾病（例如癌症）的可行治疗潜力。HSPA12B的过表达减弱了LA诱导的内皮细胞增殖和迁移的抑制作用。总体而言，结果表明LA通过下调HSPA12B / VEGF信号轴来抑制人血管内皮细胞的增殖和迁移能力。数据表明，除糖尿病并发症的治疗外，LA还可能代表对涉及血管生成活性高的人类疾病（例如癌症）的可行治疗潜力。HSPA12B的过表达减弱了LA诱导的内皮细胞增殖和迁移的抑制作用。总体而言，结果表明LA通过下调HSPA12B / VEGF信号轴来抑制人血管内皮细胞的增殖和迁移能力。数据表明，除了糖尿病并发症的治疗外，LA还可能代表对涉及血管生成活性高的人类疾病（例如癌症）的可行治疗潜力。