Endothelin Receptor-Independent Correlation Between HSP47 and Collagen in Rabbit Model of Early Atherosclerosis


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REEL B. , Cavdar Z., Ergur B. U. , Ozkal S., Ozsarlak-Sozer G. , Oktay G., et al.

TURKIYE KLINIKLERI TIP BILIMLERI DERGISI, cilt.31, ss.1330-1339, 2011 (SCI İndekslerine Giren Dergi)

  • Cilt numarası: 31 Konu: 6
  • Basım Tarihi: 2011
  • Doi Numarası: 10.5336/medsci.2010-19004
  • Dergi Adı: TURKIYE KLINIKLERI TIP BILIMLERI DERGISI
  • Sayfa Sayısı: ss.1330-1339

Özet

Objective: Collagen in the extracellular matrix (ECM) plays an important role in modulation of response to the vascular injury during the progression of atherosclerosis and restenosis. Collagen can regulate smooth muscle cell (SMC) proliferation, migration and matrix metalloproteinase (MMP) production. Therefore, collagen turnover in the arteries is an important determinant of intimal thickening. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is thought to be essential for the processing and secretion of procollagen molecules. Endothelin (ET) is a strong chemoatractant and mitogen promoting SMC proliferation and migration. The aim of this study was to investigate the possible role of HSP47 and its relation to collagen synthesis, and the effects of a nonselective ETA/ETB receptor antagonist, TAK-044 in collar-induced early atherosclerosis model. Material and Methods: New Zealand white rabbits were divided into two groups. Both groups received vehicle (0.9% NaCl 0.8 ml/kg/day, s.c.) or TAK-044 (5 mg/kg/day, s.c.) for three weeks. On 8th day, a non-occlusive silicon collar was placed around the left carotid artery. The right carotid artery was sham-operated. HSP47 expression in carotid arteries were determined immunohistochemically. Furthermore, total collagen levels, collagen expression and type I procollagen expression were established. Results: HSP47 expression correlated with collagen expression did not change in collared arteries. TAK-044 treatment did not affect HSP47 and collagen levels. Conclusion: There was a correlation between HSP47 expression and collagen expression in carotid arteries. However, intimal thickening did not induce HSP47 expression and early collagen development. The ineffectivenes of TAK-044 suggests that ET-1 signaling may not be implicated in HSP47 and collagen in this model.