Department of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, 44195, USA.
Heart Health, South Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.
Cardiovasc Diabetol. 2017 Sep 29;16(1):121. doi: 10.1186/s12933-017-0605-8.
Abnormalities of endothelial cell function are proposed to be a critical factor underlying adverse cardiovascular outcomes in the setting of hyperglycaemia. While high-density lipoproteins (HDL) have been demonstrated to be cardioprotective, the impact on the endothelium in hyperglycaemia has not been fully elucidated.
Human umbilical vein endothelial cells (HUVECs) were exposed to high-glucose conditions using dextrose, the main isoform of glucose, and native HDL. HUVEC proliferation and migration were determined. The key signalling pathways that regulate endothelial cell function were also characterized.
Increasing concentrations of dextrose resulted in significant reductions in HUVEC proliferation, this was attenuated by coincubation with HDL. In support of this, HDL was also found to rescue dextrose impaired expression of PCNA and the activation (phosphorylation) of the key transcription factor for proliferation ERK. Dextrose also dose-dependently inhibited HUVEC migration, which was mitigated by co-incubation with HDL. Consistent with this, HDL prevented dextrose-induced inhibition of p38 phosphorylation, responsible for cell migration. Finally, phosphorylation of the pro-survival transcription factor Akt was dose-dependently inhibited by dextrose, however, this was completely rescued by co-administration with HDL.
Dextrose-induced hyperglycaemia causes the impairment of endothelial cell proliferation and migration and inhibits the activation of ERK, p38 and Akt pathways. The protective effects of HDL in this milieu highlights the potential for HDL to improve vascular repair in patients with impaired glucose homeostasis.
内皮细胞功能异常被认为是高血糖导致不良心血管结局的关键因素。虽然高密度脂蛋白（HDL）已被证明具有心脏保护作用，但它对高血糖状态下内皮细胞的影响尚未完全阐明。
用人脐带静脉内皮细胞（HUVEC）的葡萄糖，葡萄糖的主要异构体和天然的高密度脂蛋白（HDL）来暴露在高血糖条件下。测定 HUVEC 的增殖和迁移。还对调节内皮细胞功能的关键信号通路进行了表征。
葡萄糖浓度的增加导致 HUVEC 增殖显著减少，而与 HDL 共孵育则减弱了这种减少。支持这一点的是，还发现 HDL 可恢复葡萄糖损害的 PCNA 表达和增殖关键转录因子 ERK 的激活（磷酸化）。葡萄糖还剂量依赖性地抑制 HUVEC 迁移，而与 HDL 共孵育则减轻了这种抑制。与此一致的是，HDL 可防止葡萄糖诱导的 p38 磷酸化抑制，p38 磷酸化负责细胞迁移。最后，促生存转录因子 Akt 的磷酸化被葡萄糖剂量依赖性抑制，但与 HDL 共同给药可完全挽救。
葡萄糖诱导的高血糖导致内皮细胞增殖和迁移受损，并抑制 ERK、p38 和 Akt 通路的激活。HDL 在这种环境中的保护作用突出了 HDL 改善葡萄糖稳态受损患者血管修复的潜力。
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