Reduced expression of perlecan in the aorta of secondary hyperparathyroidism model rats with medial calcification

Maki Shibata, Takashi Shigematsu, Ikuji Hatamura, Fumie Saji, Sachiko Mune, Ken Kunimoto, Yoshiyuki Hanba, Kazuhiro Shiizaki, Toshifumi Sakaguchi, Shigeo Negi

Research output: Contribution to journalArticle

5 Scopus citations

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 56 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. Discussion. 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.

Original languageEnglish (US)
Pages (from-to)214-223
Number of pages10
JournalRenal Failure
Volume32
Issue number2
DOIs
StatePublished - Mar 2010

Keywords

  • Heparan sulfate proteoglycan
  • Hyperparathyroidism
  • Hyperphosphatemia
  • Perlecan
  • Vascular calcification

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Nephrology

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    Shibata, M., Shigematsu, T., Hatamura, I., Saji, F., Mune, S., Kunimoto, K., Hanba, Y., Shiizaki, K., Sakaguchi, T., & Negi, S. (2010). Reduced expression of perlecan in the aorta of secondary hyperparathyroidism model rats with medial calcification. Renal Failure, 32(2), 214-223. https://doi.org/10.3109/08860220903367544