科研之友
微信
新浪微博
Facebook
分享链接
摘要
Objective: Considering the poor efficacy of local intramuscular injections with endothelial progenitor cells (EPCs) for critical limb ischemia in patients with diabetes, the study aimed to investigate the effect of alpha-tocopherol (alpha-T and alpha-tocopherol phosphate (alpha-TP) on apoptosis and angiogenesis in a rat model under oxidative stress conditions. @@@ Methods: Primary EPCs from Sprague-Dawley rats were harvested and treated with alpha-T and alpha-TP for 24 hours. Gene transcription and protein expression were evaluated by real-time polymerase chain reaction and Western blot, respectively. Cell apoptosis, migration, and tube formation ability were detected by flow cytometry, Transwell assay (Chemicon International, Temecula, Calif), and Matrigel-based angiogenesis assay (Corning Inc, Corning, NY). The in vivo experiments were carried out using 30 single hind limb ischemic models of diabetic rats that were treated with allogeneic EPCs. Capillary density was evaluated by immunohistochemistry. @@@ Results: alpha-T and alpha-TP attenuated high glucose/hypoxia-induced cell apoptosis by promoting Bcl-2 and Akt and inhibiting nuclear factor kB p65, JNK, Notch-1, and p38MAPK genes. Furthermore, alpha-T and alpha-TP promoted the transcription and expression of vascular endothelial growth factor receptor 2 and decreased the transcription and expression of Tie-2 and Notch-1 in EPCs under high-glucose/hypoxic conditions. Moreover, alpha-T and especially alpha-TP enhanced the migratory activity of EPCs under high-glucose/hypoxic conditions. Capillary density of ischemic hind limbs was increased on day 14 after administration of EPCs pretreated with alpha-T and alpha-TP. @@@ Conclusions: alpha-T, especially alpha-TP, possesses therapeutic potential in the inhibition of apoptosis and increases the migratory capacity of EPCs under high-glucose/hypoxic conditions. It promotes angiogenesis by upregulating Bcl-2, Akt, and vascular endothelial growth factor receptor 2 and decreasing nuclear factor kB p65, p38MAPK, Notch-1, JNK, and Tie-2. (J Vasc Surg 2018; 67: 1263-73.) @@@ Clinical Relevance: Considering the poor efficacy of local intramuscular injections with endothelial progenitor cells for critical limb ischemia in patients with diabetes, the study aimed to investigate the effect of alpha-tocopherol and alpha-tocopherol phosphate on apoptosis and angiogenesis in a rat model under oxidative stress conditions. alpha-Tocopherol, especially alpha-tocopherol phosphate, possesses therapeutic potential in the inhibition of apoptosis and increases the migratory capacity of endothelial progenitor cells under high-glucose/hypoxic conditions. It promotes angiogenesis by upregulating Bcl-2, Akt, and vascular endothelial growth factor receptor 2 and decreasing nuclear factor kB p65, p38MAPK, Notch-1, JNK, and Tie-2.
