Aberrant activation of Wnt pathways in arteries associates with vascular calcification in chronic kidney disease.

Abstract

Development of vascular calcification in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) leads to increased cardiovascular morbidity and mortality. The mechanism of vascular calcification in CKD patients remains unclear. This study is aimed to evaluate the clinical association between abnormal Wnt pathways and incidence of vascular calcification in ESRD patients. A total of 41 ESRD patients were enrolled in this study. Tissue samples of radial arteries were obtained during arteriovenous fistula surgery. Expression of Wnt pathways was assessed by immunohistochemistry with antibodies against catenin, GSK-3beta and Wnt-5a. Correlation analysis was performed to evaluate the association between Wnt activities and vascular calcification rates. Immunohistochemical stainings demonstrated that increased expressions of β-catenin, GSK-3beta and Wnt-5a were mostly observed in the subjects with vascular calcification. Further correlation analysis identified that β-catenin expression in overall arterial samples was significantly associated with the expressions of GSK-3beta and Wnt-5a. We also found significant correlation between expressions of GSK-3beta and Wnt-5a in the studied samples. The multivariate logistic regression analysis demonstrated that Wnt-5a was an independent risk factor for vascular calcification in patients with ESRD. Our study identifies increased activation of Wnt pathways in the arteries of patients with ESRD, which is significantly correlated with the incidence of vascular calcification. These findings support Wnt pathways as a potential target for future therapy of vascular calcification in CKD.