Basic Research in Cardiology

, Volume 104, Issue 1, pp 60–68 | Cite as

Propylthiouracil, independent of its antithyroid effect, decreases VSMC collagen expression

  • Wei-Jan Chen
  • Jong-Hwei S. Pang
  • Kwang-Huei Lin
  • Su-Hui Yang
ORIGINAL CONTRIBUTION
First Online:
Received:
Accepted:

Abstract

Propylthiouracil (PTU), in addition to its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. Because collagen accumulation is the major contributor to the growth of atherosclerotic lesions and the neointimal formation after arterial injury, the aim of this study is to investigate the impact of PTU on collagen regulation. In the rat carotid injury model, PTU administration reversed the up-regulation of collagen in the neointima induced by balloon injury. In vitro, vascular smooth muscle cells (VSMCs), the main origin of arterial collagen, were treated with PTU. Propylthiouracil caused a concentration-dependent decrease in collagen I and III steady-state protein and mRNA levels, as determined by immuno-cytochemistry, Western, and/or Northern blot analyses. Transient transfection experiments using rat type I collagen promoter construct showed that PTU failed to affect collagen gene transcription in VSMCs. Actinomycin D studies demonstrated that the half-life of collagens mRNA decreased with PTU treatment, suggesting that PTU down-regulates collagen expression predominantly at the post-transcriptional level. Taken together, these data suggest that PTU inhibits VSMC collagen production via destabilization of collagen mRNA that contributes to its beneficial effect on atherogenesis and neointimal formation after arterial injury. However, whether the destabilization of collagen may induce plaque rupture in PTU-treated arteries merits further investigation.

Keywords

atherosclerosis balloon injury collagen propylthiouracil transforming growth factor-β vascular smooth muscle cells 
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Notes

Acknowledgments

This study was supported by grants from the Chang-Gung Research Grant Foundation (G331023 and G350582) and National Science Council Grant (NSC-95-2314-B-182A-047).

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Copyright information

© Springer 2008

Authors and Affiliations

  • Wei-Jan Chen
    • 1
  • Jong-Hwei S. Pang
    • 3
  • Kwang-Huei Lin
    • 2
  • Su-Hui Yang
    • 3
  1. 1.First Cardiovascular DivisionChang Gung Memorial HospitalTao-YuanTaiwan
  2. 2.Dept. of BiochemistryChang Gung UniversityTao-YuanTaiwan
  3. 3.Graduate Institute of Clinical Medical SciencesChang Gung UniversityTao-YuanTaiwan

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