Abstract
The present study aimed to explore the role of peroxisome proliferator-activated receptor γ (PPARγ) in the development of deep vein thrombosis (DVT), as well as to discover the potential regulatory mechanism of PPARγ. Human umbilical vein endothelial cells (HUVECs) were treated with modified glycated human serum albumin (M-HSA) to mimic DVT. PPARγ expression and activity were detected using western blot analysis and the corresponding activity detection kit, respectively. Cell Counting Kit-8 and the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays were employed to detect cell viability and apoptosis, respectively. The levels of thrombosis-related factors and inflammatory cytokines were detected by ELISA. The levels of oxidative stress-related factors were determined by the corresponding commercial kits. In addition, tunicamycin (TM), the agonist of endoplasmic reticulum stress (ERS), was applied to investigate the potential mechanism. The results indicated that M-HSA caused reduced expression and activity of PPARγ in HUVECs; these effects were reversed by PPARγ overexpression, which significantly inhibited M-HSA-induced cell viability loss, cell apoptosis, inflammation and oxidative stress in HUVECs. In addition, ERS was activated following M-HSA stimulation in HUVECs, but was suppressed by PPARγ overexpression. Furthermore, TM partly abolished the protective role of PPARγ overexpression against cell viability loss, cell apoptosis, inflammation and oxidative stress in M-HSA-induced HUVECs. In summary, PPARγ antagonized M-HSA-induced HUVEC injury by suppressing the activation of ERS, which provides a novel strategy for the treatment of DVT.