VEGF Regulated Permeability Of Endothelial Cells And Drug's Inhibitory Effects In Vitro And In Vivo

The vascular permeability factor (VPF) was originally described as a tumor secreted protein which caused vascular leakage. This protein was later independently cloned and named vascular endothelial growth factor (VEGF). VEGF stimulates vascular endothelial cell growth in vitro, induces angiogensis, and enhances vascular permeability in vivo. VEGF appears to play a important role in the formation or development of many myocardial diseases (such as atherosclerosis,AS). We examine the regulation of recombinant human vascular endothelial growth factor (VEGF) on the ?51-low density lipoprotein (?51-LDL) permeability of bovine aortic endothelial cells (BAEC)~ coronary endothelial cells(BCEC). cerebral microvascular endothelial cells(BCMEC) coculture endothelial cells and smooth muscle cells (BCMEC/BCSMC) and the inhibitory effect of salvianolic acid B in vitro. We also studied the effect of VEGF/VPF on the permeability of rat brain and the inhibitory effect of salvianolic acid 13 in vivo.The main results:1.The bovine aortic endothelial cells (BAEC) were cultured to investigate the effect of recombinant human vascular endothelial growth factor (VEGF) on the low density lipoprotein (LDL) permeability. The confluence BAEC monolayers were cultured with normal medium and medium containing VEGF at various concentrations and for various time periods. The Iodine labeled low density lipoprotein (LDL) flux across the nionolayers was then performed, and the radioactivity was measured by SN-695 automatic liquid scintillation counter. Addition of purified human recombinant VEGF to the BAEC monolayers could significantly increase the permeability of the monolayer to [1251] LDL (P24h) and the effect is durable, A significant'' "'I-LDL permeabiIity was observed 45 min later. The permeabiIityincrease in I-LDL permeabiIity was observed 45 min later. The permeabiIityrate increase from 5,0l 1(). l8% to 7. 051()' 82%' The effect was strengthenedwith the increasing of dose.3. We examine the effect of recombinant human vascuIar endothelial growthfactor (VEGF) /vasGUlar permeability factor(VPF) on the permeabiIity of ratbrain and the inhibitory effect of saIvianoiic acid B in vivo. The action of VEGFin the rat brain was determined by using uItraviolet spectrophotometry toexamine Evans blue staining after injection of VEGF into r8t lateral ventric1e orinto femoral artery. The dnJg inhibitory effect was observed by injectedsalvianoIic acid B into vein or IateraI ventricIe 30 minutes before the VEGFinjection. Injection of VEGF into rat IateraI ventricle or into femoral artety dose-dependently increased the Evans blue staining of the brain, but there was nosignificantIy deference between them. SaIvianoIic acid B intravenous injection(0.1mg/ml, lL/kg) could markedIy inhibit the permeabiIity effect of VEGFhoweve...