Abstract: SA-PO859

Nrf-2 Attenuates Vascular Calcification in CKD-MBD by Suppression of Oxidative Stress

Session Information

  • Vascular Calcification
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

  • 1205 Vascular Calcification

Authors

  • Li, Yi, University of Electronic Science and Technology, Chengdu, China
  • Hong, Daqing, Sichuan Provincial People's Hospital, CHENGDU, China
  • Li, Guisen, Renal Division and Institute of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People?s Hospital, Chengdu, China
  • Wang, Li, Sichuan Provincial People's Hospital, CHENGDU, China
Background

Under pathological conditions in vascular calcication, uncontrolled production of ROS induced increased oxidase activities and impaired cellular antioxidant systems. NF-E2 p45-related factor-2 (Nrf-2) is a powerful factor to regulate oxidative stress. In our study, we aimed to validate the effect and mechanism of Nrf-2 on vascular calcification of ESRD involving oxidative stress.

Methods

We selected 36 patients admitted at the Department of Nephrology in Sichuan Provincial's Hospital between 2011 and 2012. 14 cases of age and sex matched biopsy-proven non-calcification were selected as negative control and 7 healthy volunteers as normal control. To mimick vascular calcification in ESRD, we used β-glyceophosphate to stimulate the rat vascular smooth muscle cells (RASMCs). 24 rats were randomly assigned to 4 groups: normal control group, vascular calcification group, vascular calcification with DMF treatment group and DMF treated alone group. The rattus CKD-MBD vascular calcification was induced by injection of Vitamin D3 and gavage nicotine.

Results

The blood phosphorus and iPTH in ESRD patients with vascular calcification was significantly increased. Nrf-2 expression was negaitvely correlated with vascular calcification in ESRD patients indicating by Alizarin-red S staining and immunohistological staining. To further elucidate the role of Nrf-2 in vascular calcification of CKD-MBD, we had knockdown or pharmacological blockaded Nrf-2 in rat aortic smooth cells (RASMCs) followed by hyperphosphate treatment. Then we observed that knockdown or pharmacological blockade Nrf-2 could induce vascular calcification in CKD-MBD. Nrf-2 agonist treatment showed that activation Nrf-2 could ameliorate vascular calcification in RASMCs. Then ROS inhibitor NAC pretreatment increased the level of Nrf-2 and ameliorated vascular calcification in RASMCs. Activation of Nrf-2 inhibited oxidative stress and attenuated mitochondria injury in RASMCs upon vascular calcification. Pathological examination reaveled that Nrf-2 agonist could suppress vascular calcification in rat CKD aortas. Immunohistological staining about Nrf-2 indicated that calcified rat aortas decreased the expression of Nrf-2. However, DMF increased the expression of Nrf-2 in vascular calcification rat aortas.

Conclusion

These resluts might indicate Nrf-2 attenuates vascular calcification in CKD-MBD by suppression of oxidative stress.