Reduced Expression of Perlecan in the Aorta of Secondary Hyperparathyroidism Model Rats with Medial Calcification
Autor: | Yoshiyuki Hanba, Maki Shibata, Ikuji Hatamura, Toshifumi Sakaguchi, Shigeo Negi, Takashi Shigematsu, Fumie Saji, Sachiko Mune, Ken Kunimoto, Kazuhiro Shiizaki |
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Rok vydání: | 2010 |
Předmět: |
Male
medicine.medical_specialty endocrine system diseases medicine.medical_treatment Cell Culture Techniques Perlecan Critical Care and Intensive Care Medicine Nephrectomy Muscle Smooth Vascular Rats Sprague-Dawley Hyperphosphatemia Risk Factors Internal medicine medicine.artery medicine Animals Aorta Abdominal Hyperparathyroidism Aorta biology Reverse Transcriptase Polymerase Chain Reaction business.industry Abdominal aorta Calcinosis General Medicine Microarray Analysis medicine.disease Immunohistochemistry Diet Rats Disease Models Animal Endocrinology Nephrology biology.protein Hyperparathyroidism Secondary Secondary hyperparathyroidism business Biomarkers Heparan Sulfate Proteoglycans |
Zdroj: | Renal Failure. 32:214-223 |
ISSN: | 1525-6049 0886-022X |
Popis: | Vascular calcification is an important complication that worsens the prognosis for dialysis patients, although its detailed molecular mechanisms are still unknown.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.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.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.It may be that reduced expression of perlecan in the calcified aortae of hyperparathyroid rats is a risk factor for vascular calcification. |
Databáze: | OpenAIRE |
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