Abstract: TH-PO987
The Soluble VEGF Receptor sFlt-1 Contributes to Endothelial Dysfunction in IgA Nephropathy
Session Information
- Glomerular Diseases: Minimal Change Disease, FSGS, IgAN
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Zhai, Yaling, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Dou, Yanna, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Xiao, Jing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Zhao, Zhanzheng, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Background
Endothelial injury is a common manifestation in IgA nephropathy (IgAN). After the previous identification of the upregulated soluble fms-like tyrosine kinase-1 (sFlt-1) correlates with endothelial injury in IgAN, in the present study, we further explored the role of sFlt-1 in endothelial injury in IgAN.
Methods
We enrolled 72 patients with IgAN and detected the sFlt-1 levels. The polymeric IgA1 (pIgA1) complexes were isolated from the pooled plasma samples of another 10 patients with IgAN. Apoptosis proteins were detected in cultured human umbilical vein endothelial cells (HUVECs) with recombinant sFlt-1 or the caspase-9 inhibitor, Z-LEHD-FMK stimulation.
Results
We identified there were positive correlations between sFlt-1 and IgA-IgG complex as well as vWF levels in patients with IgAN. The sFlt-1 levels in HUVECs were significantly upregulated by pIgA1 complex derived from IgAN patients in a concentration-dependent manner. The proliferation ability of HUVECs was damaged when stimulated by sFlt-1 protein in a time- and dose- dependent manner. And the apoptosis rate was up-regulated significantly as the stimulation concentration of sFlt-1 increased. We found sFlt-1 challenge could significantly increase the expression of vWF and ET-1. In addition, sFlt-1 could increase the levels of caspase-9, caspase-3, Bax and mitochondrial membrane potential; facilitate the release of cytochrome C from mitochondria to cytoplasma. In contrast, Z-LEHD-FMK attenuated high sFlt-1-induced HUVECs apoptosis.
Conclusion
Our study demonstrated that sFlt-1 expression was up-regulated by challenged by pIgA1 complex derived from patients with IgAN, which then facilitated human umbilical vein endothelial cells apoptosis through the mitochondrial-dependent pathway.
Funding
- Clinical Revenue Support