| Purpose:To observe the endogenous VEGF-A expression in vein graft adaptation and the regulation of venous marker EphB4,so as to discuss the mechanism role of VEGF-A in inhibiting vein graft intimal hyperplasia by regulating EphB4.Methods:Establish mouse auto-jugular vein graft model to determine VEGF-AmRNA, EphB4mRNA level in early and late phase as well as compare vascular wall thickening in vein graft adaptation; Knockdown endogenous VEGF-A in early phase by using siRNA and observe EphB4expression and tendency of intima-media thickening in later phase. Morphometry method was used to determine the difference between groups.Results:Knockdown endogenous VEGF-A by using siRNA lead to increase of intima-media thickening; early reduction in VEGF-A levels change later EphB4exprssionConclusion:VEGF is required for diminshed EphB4exprssion in vein graft. The mechanism role of VEGF-A inhibit intimal hyperplasia may via downregulation of EphB4. Background:Vein graft adaptation is characterized by both increased expression of VEGF-A, a stimulator of angiogenesis, as well as decreased expression of Eph-B4, a marker of venous identity. To determine whether VEGF-A is a potential mechanism responsible for diminished Eph-B4expression in adult veins, we examined whether VEGF-A regulates Eph-B4expression in venous endothelial cells.Methods:Murine endothelial cells were stimulated with VEGF-A, or pretreated with VEGF-R2, ERK1/2, or Akt inhibitors, and then Eph-B4expression was determined by qPCR.Results:VEGF-A down-regulated Eph-B4in a time-and dose-dependent fashion, and with a similar course as upregulation of Ephrin-B2. VEGF-A suppression of Eph-B4expression was dependent, at least in part, on VEGFR2and its downstream extracellular signal-regulated kinase (ERK)-1/2pathway but not the Akt pathway.Conclusions:VEGF-A directly downregulates Eph-B4in adult venous endothelial cells by VEGFR2-ERK1/2pathway. These results suggest additional mechanisms to control wall thickness during vein graft adaptation. |
PDF Full Text Request