Artery calcification in uremic rats is increased by a low protein diet and prevented by treatment with ibandronate.
The present experiments investigate medial artery calcification in adult rats made uremic by feeding a synthetic diet containing 0.75% adenine for 4 weeks. Calcification was assessed by Alizarin red staining of intact aortas, by von Kossa staining of carotid artery sections, and by calcium and phosphate incorporated into the thoracic aorta. The major conclusions are as follows: Lowering the protein content of the diet from 25 to 2.5% dramatically increases the frequency and extent of medial artery calcification in uremic rats without significantly affecting the elevation in serum creatinine, phosphate, or parathyroid hormone. This observation suggests that low dietary protein intake could be a risk factor for medial artery calcification in uremic patients. Medial artery calcification in uremic rats is prevented by a dose of ibandronate that inhibits bone resorption. The observation suggests that bone resorption inhibitors could prevent artery calcification in uremic patients. Medial artery calcification in uremic rats correlates with increased serum bone Gla protein (BGP; osteocalcin), but not with serum matrix Gla protein or fetuin. This finding indicates that it could be of interest to examine the relation between serum BGP and artery calcification in uremic patients. Each of these conclusions lends support for our hypothesis that medial artery calcification is linked to bone resorption. Future investigations of the as yet unknown biochemical basis for this link will be facilitated by the present discovery that a synthetic, 2.5% protein diet containing 0.75% adenine produces consistent and dramatic medial calcification in adult rats within just 4 weeks.
Price
P A
PA
Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0368, USA. pprice@ucsd.edu
Roublick
A M
AM
Williamson
M K
MK
D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology; D002114:Calcinosis / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D002135:Calcium-Binding Proteins / Q000097:blood; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004044:Dietary Proteins / Q000494:pharmacology; D004164:Diphosphonates / Q000627:therapeutic use*; D016326:Extracellular Matrix Proteins / Q000097:blood; D000077557:Ibandronic Acid; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology; D014511:Uremia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D014652:Vascular Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D000509:alpha-Fetoproteins / Q000032:analysis; D000097568:Matrix Gla Protein
D050071:Bone Density Conservation Agents; D002135:Calcium-Binding Proteins; D004044:Dietary Proteins; D004164:Diphosphonates; D016326:Extracellular Matrix Proteins; D000077557:Ibandronic Acid; D015675:Osteocalcin; D000509:alpha-Fetoproteins; D000097568:Matrix Gla Protein