Phosphorus overload and PTH induce aortic expression of Runx2 in experimental uraemia.
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.
Graciolli
Fabiana G
FG
Nephrology Division, Department of Internal Medicine, University of São Paulo, São Paulo, Brazil.
Neves
Katia R
KR
dos Reis
Luciene M
LM
Graciolli
Rafael G
RG
Noronha
Irene L
IL
Moysés
Rosa M A
RM
Jorgetti
Vanda
V
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D002114:Calcinosis / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009392:Nephrectomy; D053244:Osteoprotegerin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D016105:Parathyroidectomy; D010641:Phenotype; D010758:Phosphorus / Q000008:administration & dosage / Q000378:metabolism*; D016226:Phosphorus, Dietary; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D014511:Uremia / Q000378:metabolism* / Q000473:pathology
D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary; C493717:Runx2 protein, rat; D010758:Phosphorus