Abstract: SA-PO867

Endothelial Hyperpermeability Induced by Mineral Stress Is Involved in the Development of Medial Layer Vascular Calcification

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

  • Shikida, Yasuto, Showa University School of Medicine, Tokyo, Japan
  • Mizobuchi, Masahide, Showa University School of Medicine, Tokyo, Japan
  • Ogata, Hiroaki, Showa University Northern Yokohama Hospital, Yokohama, Japan
  • Koiwa, Fumihiko, Showa University Fujigaoka Hospital, Yokohama, Japan
  • Shibata, Takanori, Showa University School of Medicine, Tokyo, Japan
Background

Mineral stress such as high calcium and/or phosphate induces vascular calcification (VC) in chronic kidney disease. Although investigations regarding VC are growing, the precise mechanisms underlying the development of VC by the mineral stress remain to be studied. We investigated the role of vascular endothelial cell (EC) function in medial layer VC.

Methods

Human Umbilical Endothelial Cells (HUVEC) and aortic rings from normal and 5/6 nephrectomized uremic rats were used. Mineral stress was induced by a high calcium (3.6 mM) and phosphate (2.2 mM) media to HUVEC and aortic rings. Thereafter permeability and EC markers (CD31, VE-cadherin, and ZO-1) of HUVEC, and calcium contents and EC markers of aortic rings were studied. Alizarin red staining was also performed to evaluate the localization of mineral deposition in the rings. Regular media was utilized as control groups in each experiment.

Results

The mineral stress significantly increased permeability of HUVEC (2.5-fold to control, p<0.05) in conjunction with a significant decrease in mRNA levels of EC markers (CD31:0.5-fold to control, p<0.01, VE-cadherin: 0.7-fold to control, p<0.05, and ZO-1: 0.7-fold to control, p<0.05). The mineral stress also significantly increased calcium content in the aortic rings of normal (p<0.05 vs control) and uremic rats (p<0.05 vs control), respectively. A similar tendency was observed for EC markers in the rings of normal and uremic rats, respectively. Alizarin red staining showed medial layer mineral deposition of the aortic rings. (Figure: the ring of a uremic rat with the mineral stress).

Conclusion

Hyperpermeability of vascular ECs was induced by mineral stress indicating that loss of barrier function of ECs might have a crucial role in the development of medial layer VC.

Funding

  • Private Foundation Support