Abstract: SA-PO873

Activation of the mTORC1 Pathway by Inflammation Contributes to Vascular Calcification in Patients with ESRD

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

Author

  • Jing, Liu, Institute of Nephrology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
Background

Chronic inflammation plays an important role in the progression of vascular calcification (VC). This study was designed to explore the effects and underlying mechanisms of inflammation on VC in the radial arteries of patients with end-stage renal disease (ESRD) with arteriovenostomy.

Methods

Forty-eight ESRD patients were divided into control (n=25) and inflamed groups (n=23) according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in this study. Alizarin Red S staining was used to examine calcium deposition. The expression of inflammation markers, bone structure-associated proteins and mammalian target of rapamycin complex1 (mTORC1) pathway-related proteins were assessed by immunohistochemical staining.

Results

The expression of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) was increased in the radial arteries of the inflammation group. Additionally, Alizarin Red S staining revealed an obvious increase in calcium deposition in the inflammation group compared to that in the control group. Further analysis by immunohistochemical staining demonstrated that the deposition was correlated with the increased expression of bone-associated proteins such as bone morphogenetic proteins-2 (BMP-2) and osteocalcin and collagen I, which suggested that inflammation induces osteogenic differentiation in vascular tissues and that osteogenic cells are the main cellular components involved in VC. Interestingly, there was a parallel increase in the expression of phosphorylated mTOR (p-mTOR) and p-ribosomal protein S6 kinase 1 (p-S6K1) in the inflammation group. Furthermore, mTORC1 pathway-related proteins were significantly associated with the enhanced expression of bone formation biomarkers.

Conclusion

Inflammation contributed to VC in the radial arteries of ESRD patients via the induction of osteogenic differentiation in vessel walls, which could be regulated by the activation of the mTORC1 pathway.

Funding

  • Government Support - Non-U.S.