title: Reduced expression of perlecan in the aorta of secondary hyperparathyroidism model rats with medial calcification.
abstract: BACKGROUND
  Vascular calcification is an important complication that worsens the prognosis for dialysis patients, although its detailed molecular mechanisms are still unknown.
  
  
  METHODS
  We produced a rat model for vascular calcification with hyperphosphatasemia and hyperparathyroidism, performing a 5/6 nephrectomy and providing a high-phosphorus, low-calcium diet for eight weeks. We examined mRNA obtained from the calcified aortae using microarray analysis, and searched for alterations in gene expression specifically in the calcified lesions.
  
  
  RESULTS
  Medial calcification was demonstrated in the abdominal aorta of 12 out of 42 hyperparathyroidism rats. In the aortae of hyperparathyroid rats with vascular calcification, the genes for heparan sulfate proteoglycans, including perlecan, were found to be down-regulated using microarray analysis and real time PCR. Immunohistochemistry also demonstrated reduced production of perlecan in the aortae of hyperparathyroid rats.
  
  
  CONCLUSIONS
  Perlecan is a major component of the vascular wall basement membrane and may play a role in protecting vascular smooth muscle cells from inflammatory cells and various toxins. It has also been reported that heparan sulfate chains may inhibit osteogenesis. Our findings indicate that perlecan may protect vascular smooth muscle cells from various factors that promote vascular calcification.
  
  
  CONCLUSIONS
  It may be that reduced expression of perlecan in the calcified aortae of hyperparathyroid rats is a risk factor for vascular calcification.
authors.affiliation: Division of Nephrology, International Medical Center of Japan, Wakayama Medical University, Wakayama, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Shibata
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigematsu
authors.forename: Ikuji
authors.initials: I
authors.lastname: Hatamura
authors.forename: Fumie
authors.initials: F
authors.lastname: Saji
authors.forename: Sachiko
authors.initials: S
authors.lastname: Mune
authors.forename: Ken
authors.initials: K
authors.lastname: Kunimoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hanba
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiizaki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Negi
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D004032:Diet; D004195:Disease Models, Animal; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism* / Q000473:pathology; D054559:Hyperphosphatemia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan