Department of Interventional Radiology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, No 600 Yishan road, Xuhui District, Shanghai, 200233, China.
Department of Interventional Radiology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, No 600 Yishan road, Xuhui District, Shanghai, 200233, China.
Biomed Pharmacother. 2018 Jul;103:290-300. doi: 10.1016/j.biopha.2018.04.039. Epub 2018 Apr 24.
The activity of glucagon-like peptide 1 (GLP-1R) is essential for preventing restenosis following vascular injury; however, the mechanism of dysfunctional GLP-1R glycosylation and ways to enhance the activity of GLP-1R on vascular surfaces in diabetic patients are poorly understood. In the present study, we investigated the N-glycosylation level and role of stress-associated endoplasmic reticulum protein 1 (SERP1) in preventing restenosis following carotid injury in diabetic rats. Our results showed that N-glycosylation levels in both rat aortic endothelial cells (RAOECs) and rat vascular smooth muscle cells (VSMCs) decreased gradually following glucose treatment in a concentration dependant manner. Furthermore, co-immunoprecipitation (Co-IP) analyses indicated that SERP1 could interact with GLP-1R in RAOECs and VSMCs. Moreover, SERP1 enhanced GLP-1R N-glycosylation and increased the production of phosphorylated endothelial nitric oxide synthase (eNOS) as well as proliferation of RAOECs. SERP1 also increased phosphorylated adenosine monophosphate activated protein kinase (AMPK) and decreased the migration of VSMCs. Importantly, intima media thickness (IMT) and neointimal hyperplasia were alleviated in the carotid artery of diabetic rats injected with SERP1 following balloon injury. We also found an increase in re-endothelialization and a decrease in VSMC proliferation in the carotid artery of diabetic rats injected with SERP1. In summary, the remarkable effects of SERP1 on reducing restenosis following vascular injury may contribute to future advancements in the treatment of diabetic vascular complications.
胰高血糖素样肽 1（GLP-1R）的活性对于防止血管损伤后的再狭窄至关重要；然而，功能失调的 GLP-1R 糖基化的机制以及在糖尿病患者中增强 GLP-1R 在血管表面活性的方法还知之甚少。在本研究中，我们研究了应激相关内质网蛋白 1（SERP1）在糖尿病大鼠颈动脉损伤后防止再狭窄中的 N-糖基化水平和作用。我们的结果表明，在葡萄糖处理下，大鼠主动脉内皮细胞（RAOECs）和大鼠血管平滑肌细胞（VSMCs）中的 N-糖基化水平逐渐降低，呈浓度依赖性。此外，免疫共沉淀（Co-IP）分析表明 SERP1 可以在 RAOECs 和 VSMCs 中与 GLP-1R 相互作用。此外，SERP1 增强了 GLP-1R 的 N-糖基化，增加了磷酸化内皮型一氧化氮合酶（eNOS）的产生以及 RAOECs 的增殖。SERP1 还增加了磷酸化的腺苷单磷酸激活蛋白激酶（AMPK）的产生，减少了 VSMCs 的迁移。重要的是，在球囊损伤后向糖尿病大鼠颈动脉内注射 SERP1 可减轻内膜中层厚度（IMT）和新生内膜过度增生。我们还发现，在向糖尿病大鼠颈动脉内注射 SERP1 后，再内皮化增加，VSMC 增殖减少。总之，SERP1 对减少血管损伤后再狭窄的显著作用可能有助于糖尿病血管并发症治疗的未来进展。
