Role Of Nuclear Factor-κB Signal Transduction Pathway In The Pathogenesis Of Portal Hypertensive Vasculopathy

Objective:The present study was designed to investigate the activation of local nuclear factor-Kappa B(NF-κB) and the expression of local angiotensinogen, tumor necrosis factor alpha(TNF-α) and matrix Gla protein(MGP) mRNA in splenic artery and vein of portal hypertensive patients and to discuss Role of nuclear factor- Kappa B signal transduction pathway in the pathogenesis of portal hypertensive vasculopathy.Method:Chemiluminescent electrophoretic mobility shift assay(EMSA) was used to detect the activation of NF-κB in splenic artery and vein of portal hypertensive patients and normal vascular. The expression of local angiotensinogen, tumor necrosis factor alpha(TNF-α) and matrix Gla protein(MGP) mRNA in splenic artery and vein of portal hypertensive patients and normal vascular were detected by RT-PCR analysis. Splenic artery and vein of portal hypertensive patients and normal vascular were observed under optic and electron microscopes.Results:The activation of NF-κB in splenic artry and vein of portal hypertensive patients(1.44±0.23),(1.38±0.18) was observed significantly higher than that in control group(0.19±0.20),(0.25±0.16)(P<0.05). Levels of local angiotensinogen mRNA in splenic artery and vein of portal hypertensive grpup were (0.48±0.21),(0.43±0.16), Respectively significantly higher than that in control group(0.23±0.12,0.18±0.10)(all P<0.05). Expression of TNF-αmRNA in splenic artery and vein of portal hypertensive group was (0.38±0.21),(0.36±0.16),respectively, significantly higher than that in control group(0.24±0.12,0.21±0.10)(all P<0.05), and the expression of TNF-αmRNA in splenic artery and vein of portal hypertensive patients had a significant positive correlation with the activity of NF-κB(r=0.796,P<0.05;r=0.849,P<0.05, respectively). Expression of MGP mRNA in splenic artery and vein of portal hypertensive group was (0.58±0.19),(0.55±0.15),respectively,significantly higher than that in control group(0.23±0.10,0.26±0.13 )(all P<0.05). There was no significant difference between the splenic artery and vein in the expression of local angiotensinogen, TNF-αand MGP mRNA in portal hypertensive group. Compare with normal vascular we found a large number of hypertrophic and proliferative smooth muscle cells in the Splenic artery and vein of portal hypertensive patients,some of them migrated to the subintima;cell organ pert biosynthesis increased.Conclusion:The activation of NF-κB increased in splenic artry and vein of portal hypertensive patients,which indicated that NF-κB signal transduction pathway may play an important role in the pathogenesis of portal hypertensive vasculopathy. Local angiotensinogen and TNF-αand activation of NF-κB maybe the factors in the pathogenesis of portal hypertensive vasculopathy,which can cause and to advance portal hypertensive vasculopathy.Significant expression of MGP mRNA in splenic artery and vein of PHT can regulate proliferation and migration of the vascular smooth muscle cell(VSMC),and MGP was the marker gene of VSMC phenotype,which can also cause and to advance portal hypertensive vasculopathy.