Phosphorus overload and PTH induce aortic expression of Runx2 in experimental uraemia

Autor(es)

Graciolli, Fabiana G. ; Neves, Katia R. ; dos Reis, Luciene M. ; Graciolli, Rafael G. ; Noronha, Irene L. ; Moyses, Rosa M. A. ; Jorgetti, Vanda ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Internal Med, Div Nephrol, Lab Fisiopatol Renal LIM 16, BR-01246903 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Nephrology Dialysis Transplantation; v. 24, n. 5, p. 1416-1421, MAY 2009.
• Citações Web of Science: 39

Resumo

Background. Vascular calcification (VC) is commonly seen in patients with chronic kidney disease (CKD). Elevated levels of phosphate and parathormone (PTH) are considered nontraditional risk factors for VC. It has been shown that, in vitro, phosphate transforms vascular smooth muscle cells (VSMCs) into calcifying cells, evidenced by upregulated expression of runt-related transcription factor 2 (Runx2), whereas PTH is protective against VC. In addition, Runx2 has been detected in calcified arteries of CKD patients. However, the in vivo effect of phosphate and PTH on Runx2 expression remains unknown. Methods. Wistar rats were submitted to parathyroidectomy, 5/6 nephrectomy (Nx) and continuous infusion of 1-34 rat PTH (at physiological or supraphysiological rates) or were sham-operated. Diets varied only in phosphate content, which was low (0.2%) or high (1.2%). Biochemical, histological, immunohistochemistry and immunofluorescence analyses were performed. Results. Nephrectomized animals receiving high-PTH infusion presented VC, regardless of the phosphate intake level. However, phosphate overload and normal PTH infusion induced phenotypic changes in VSMCs, as evidenced by upregulated aortic expression of Runx2. High-PTH infusion promoted histological changes in the expression of osteoprotegerin and type I collagen in calcified arteries. Conclusions. Phosphate, by itself is a potential pathogenic factor for VC. It is of note that phosphate overload, even without VC, was associated with overexpression of Runx2 in VSMCs. The mineral imbalance often seen in patients with CKD should be corrected. (AU)

• Processo FAPESP: 03/14158-3 - Estudo de proteínas envolvidas no processo de calcificação óssea e extra-óssea em ratos urêmicos paratireoidectomizados, submetidos a dieta rica e pobre em fósforo associada a infusão fixa de paratormônio
• Beneficiário: Vanda Jorgetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular