Reduced expression of perlecan in the aorta of secondary hyperparathyroidism model rats with medial calcification.
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.
Shibata
Maki
M
Division of Nephrology, International Medical Center of Japan, Wakayama Medical University, Wakayama, Japan.
Shigematsu
Takashi
T
Hatamura
Ikuji
I
Saji
Fumie
F
Mune
Sachiko
S
Kunimoto
Ken
K
Hanba
Yoshiyuki
Y
Shiizaki
Kazuhiro
K
Sakaguchi
Toshifumi
T
Negi
Shigeo
S
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
D015415:Biomarkers; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan