Abstract: SA-PO360

The Role of Renal Vascular Endothelial-Mesenchymal Transition in Systemic Lupus Erythematosus Associated Thrombotic Microangiopathy

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Hu, Weixin, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
  • Zhou, Ying, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
  • Chen, Ying-hua, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
  • Zhang, Ming-chao, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
  • Liang, Shao-shan, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
  • Yang, Fan, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
  • Liu, Zheng-zhao, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
  • Liu, Zhi-Hong, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing China, Nanjing, China
Background

To investigate the phenotypic changes of renal vascular endothelial cells and its relationship with the vascular injury and renal interstitial fibrosis in patients with SLE associated thrombotic microangiopathy (SLE-TMA).

Methods

Biopsies from 30 SLE patients which showed lupus nephritis and renal vascular TMA were included in this study. TMA was divided into acute and chronic TMA groups according to the histology. The expression of vascular endothelial CD31, vessel endothelial cadherin (VE-cadherin) ,α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) were stained with immunofluorescence and immune histochemical assays, the intensity of endothelial marker expression recorded as the mean density (integral optical density/ area of vascular endothelial layer) and the extent of renal interstitial fibrosis were quantitatively analyzed with Image-Pro-Plus 6.0 and ImageScope (Aperio) respectively.

Results

Confocal immunofluorescence microscopy demonstrated no α-SMA expression in endothelial cells in normal renal vessels but markedly higher endothelial α-SMA expression in renal vessels showing TMA.Compared with the normal group, the intensity of endothelial CD31 and VE-cadherin expression was significantly lower (P<0.05), and α-SMA expression was much higher (P<0.001) in acute TMA group. The endothelial CD31, VE-cadherin and TGF-β expression were significantly lower, while the α-SMA expression significantly higher in chronic TMA group than that in acute TMA group and normal group (P<0.001). The intensity of endothelial α-SMA expression was positively correlated with the extent of renal interstitial fibrosis (r=0.439, P<0.05), while the endothelial CD31 expression was negatively correlated with renal interstitial fibrosis (r=-0.458,P<0.05). Furthermore, endothelial α-SMA expression was also an independent risk factor for the poor treatment response in patients with SLE-TMA.

Conclusion

In SLE-TMA, the lower expression of normal endothelial cell markers and higher α-SMA expression indicated a pathogenetic process of vascular endothelial to mesenchymal transition, which was related with renal interstitial fibrosis and poor treatment response.