MPS 07-02 THE ACTIVATION OF BMP-WNT/β- CATENIN PATHWAY IN THE 5/6 NEPHRECTOMIZED UREMIC RAT MIGHT PLAY A ROLE IN THE VASCULAR MEDIAL CALCIFICATION AND ITS ACTIVATION IS SUPPRESSED BY PARICALCITOL, REDUCING VASCULAR MEDIAL CALCIFICATION

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Abstract

Objective:

Vascular medial calcification is closely associated with cardiovascular disease. Various mechanisms were suggested and recently, the differentiation of vascular smooth muscle cells into an osteoblast like phenotype is thought to play an important role. In this study, we aimed to test the role of the BMP-Wnt/β-catenin pathway, whose main role is involved in the normal osteogenic bone formation, and the effect of its blockade by paricalcitol on the vascular medial calcification using 5/6 nephrectomized uremic rat undergoing peritoneal dialysis (PD).

Design and Method:

Rats with 5/6 nephrectomy that underwent PD were randomly allocated to PD only and PD with paricalcitol treated (PD + Pc) group. After 8 weeks of dialysis, thoracic aortas were harvested. Vascular medial calcification was identified using the von-Kossa staining and activation of BMP-Wnt/β-catenin pathway was identified by the mRNA expression of BMP, Runx2 and immunohistochemical staining of intranuclear β-catenin. All the stained results were quantified by an image analyzer.

Results:

In the von-Kossa staining, the % positive area was significantly increased in the PD only group compared to the normal aging control group (21.17 ± 3.37 VS 1.97 ± 0.01, p = 0.004), and decreased in the PD + Pc group (12.36 ± 1.67 VS 21.17 ± 3.37, p = 0.020). The mRNA expression of BMP was increased in the PD only group and decreased in the PD + Pc group, when compared to the normal aging control group (p = 0.013). The % positive area of intranuclear β-catenin was also increased in the PD only group compared to the normal aging control group (6.76 ± 1.31VS 1.37 ± 0.31, p < 0.001) and decreased in the PD + Pc group (1.71 ± 0.36 VS 6.76 ± 1.31, p = 0.002). The mRNA expression of Runx2, which is a master gene regulator of calcification, also showed the same trend (p = 0.003).

Conclusions:

The activation of BMP-Wnt/β-catenin pathway might play a role in the vascular medial calcification and its expression is suppressed by paricalcitol, reducing vascular medial calcification in the 5/6 nephrectomized rat undergoing PD.

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