Dysfunction of endothelial progenitor cells (EPCs) contributes to cardiovascular complications in diabetes, and resveratrol has been shown to improve EPC functions. Syndecan-4 (Synd4), a cell surface heparin sulfate proteoglycan, has been shown to promote neovascularization. Thus, the present study was performed to determine whether resveratrol promoted angiogenesis of EPCs by regulating Synd4. Late EPCs were isolated from human peripheral blood and stimulated with AGEs. Western blot showed that AGEs induced Synd4 shedding in a dose- and time-dependent manner. AGE-induced Synd4 shedding was partly reversed by NAC or resveratrol, along with normalized ROS production. Overexpression of Synd4 or pretreatment of resveratrol reversed AGE-impaired tube formation of EPCs and regulated the Akt/eNOS pathway. Furthermore, resveratrol suppressed Synd4 shedding via the inhibition of oxidative stress and improved tube formation of late EPCs via the regulation of the Synd4/Akt/eNOS pathway.
Keyphrases
- endothelial cells
- high glucose
- diabetic rats
- oxidative stress
- peripheral blood
- transcription factor
- cell proliferation
- signaling pathway
- cell surface
- dna damage
- vascular endothelial growth factor
- cardiovascular disease
- type diabetes
- pi k akt
- cell death
- venous thromboembolism
- risk factors
- growth factor
- glycemic control
- reactive oxygen species
- induced pluripotent stem cells
- wound healing