High phosphorus diet induces vascular calcification, a related decrease in bone mass and changes in the aortic gene expression.
In chronic kidney disease, hyperphosphatemia has been associated to vascular calcifications. Moreover, the rate and progression of vascular calcification have been related with the reduction of bone mass and osteoporotic fractures, hereby suggesting a strong link between vascular calcification and bone loss. Our aim was to prospectively study the effects of high phosphorus diet on bone mass, vascular calcification and gene expression profile of the arterial wall. A rat model of 7/8 nephrectomy fed with normal (0.6%) and moderately high (0.9%) phosphorus diet was used. Biochemical parameters, bone mineral density and vascular calcifications were assessed. A microarray analysis of the aortic tissue was also performed to investigate the gene expression profile. After 20 weeks, the rats fed with a high phosphorus diet showed a significant increase in serum phosphorus, PTH, and creatinine, together with aortic calcification and a decrease in bone mass. The histological analysis of the vascular calcifications showed areas with calcified tissue and the gene expression profile of this calcified tissue showed repression of muscle-related genes and overexpression of bone-related genes, among them, the secreted frizzled related proteins, well-known inhibitors of the Wnt pathway, involved in bone formation. The study demonstrated prospectively the inverse and direct relationship between vascular calcification and bone mass. In addition, the microarrays findings provide new information on the molecular mechanisms that may link this relationship.
Román-García
Pablo
P
Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Universidad de Oviedo. Oviedo, Asturias, Spain.
Carrillo-López
Natalia
N
Fernández-Martín
José Luis
JL
Naves-Díaz
Manuel
M
Ruiz-Torres
María Piedad
MP
Cannata-Andía
Jorge B
JB
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003720:Densitometry; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010758:Phosphorus / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D014652:Vascular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D010758:Phosphorus