ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO495

Nox1 Induces Osteoblastic Transition of Vascular Smooth Muscle Cells and Contributes to Vascular Calcification in Early CKD Rats with Normal Serum Phosphorus

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Author

  • Xu, Hui, Nephrology Department, Xiangya Hospital, Central South University, Changsha, Hunan, China, ChangSha, China
Background

Vascular calcification (VC) is a major cause of mortality in patients with chronic kidney disease (CKD). While higher levels of serum phosphorus contribute to VC, but in early CKD patients with normal phosphorus have VC, and reduction of serum P by using various P binder is not effective in preventing VC progression in patients with CKD. So, we think some other factors contribute to VC, especially in Early CKD.

Methods

In CKD dialysis patients with VC (n=11) and dialysis CKD patients without VC (n=13), serum 8-OHdG was measured . We use CKD5 and early CKD rats to test the Vascular calcification and Nox1 , we also use the serum of early CKD patients to incubate primary
VSMCs
, SM22α expression and RUNX2 expression , calcium deposition in primary rat VSMCs and Nox1 are measured.

Results

In a rat model for the stage 5 CKD (CKD5), robust increases of VC and 8-OHdG, significant reductions of smooth muscle 22 alpha (SM22α) expression, and an upregulation in RUNX2 expression in vascular smooth muscle cells (VSMCs) were demonstrated. Inhibition of 8-OHdG using MnTMPyP dramatically reduced these events without normalization hyperphosphatemia. In CKD patients with VC (n=11) but not in CKD patients without VC (n=13), 8-OHdG was significantly elevated. While the serum levels of calcium and phosphate were not altered in animal models in the early stage CKD (ECKD), 8-OHdG, VC, SM22α downregulation, RUNX2 upregulation, and NADPH oxidase 1 (NOX1) expression in VSMCs were all significantly changed. More importantly serum (10%) derived from patients with ECKD (n=30) or CKD5 (n=30) significantly induced SM22α downregulation, RUNX2 upregulation, NOX1 upregulation along with a robust 8-OHdG, and calcium deposition in primary rat VSMCs. These alterations were all reduced by MnTMPyP and a specific NOX1 inhibitor (ML171).

Conclusion

Collectively, we provide evidence for an important role of Nox1 in promoting VC development in early CKD patients, which was at least in part through induction of osteoblastic transition in VSMCs.

Funding

  • Government Support - Non-U.S.