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Heparin/endothelial cell growth supplement regulates matrix gene expression and prolongs life span of vascular smooth muscle cells through modulation of interleukin-1

  • Growth, Differentiation, And Senescence
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Summary

Vascular smooth muscle cells produce and respond to interleukin-1, a cytokine which modifies inflammation-associated vascular activities including the synthesis of extracellular matrix proteins. We have established vascular smooth muscle cells culture conditions in which heparin, in the presence of endothelial cell growth supplement, promotes cell proliferation and inhibits interleukin-1 and matrix protein expression. To test whether interleukin-1 mediates growth and matrix modulation by heparin/endothelial cell growth supplement, vascular smooth muscle cells were transfected with an Epstein-Barr virus-derived expression vector designed to express interleukin-1 antisense transcripts. RNase protection and ELISA assays demonstrated a complete block of interleukin-1 transcription and protein synthesis. Northern blot analysis also showed that interleukin-1 antisense decreased the expression of matrix genes such as type I collagen, fibronectin, and decorin similar to downregulation after heparin/endothelial cell growth supplement treatment. In contrast, the expression of versican was not affected, indicating a selective suppression of matrix proteins. In addition, interleukin-1 antisense significantly prolonged the life span of vascular smooth muscle cells in culture. Our data suggest that heparin/endothelial cell growth supplement induces matrix remodeling and controls growth and senescence of vascular smooth muscle cells through down-regulation of interleukin-1.

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  1. Thomas Sorger

    Present address: Sidney Kimmel Cancer Center, 10835 Altman Row, Suite 240, 92121, San Diego, California

  2. Ju-Yu Hsu

    Present address: Department of Biology, Roger Williams University, One Old Ferry Road, 02809, Bristol, Rhode Island

Authors and Affiliations

  1. The Wistar Institute, 3601 Spruce Street, 19104-4268, Philadelphia, Pennsylvania

    Ju-Yu Hsu, Mei-Yu Hsu, Thomas Sorger, Meenhard Herlyn & Elliot M. Levine

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Hsu, JY., Hsu, MY., Sorger, T. et al. Heparin/endothelial cell growth supplement regulates matrix gene expression and prolongs life span of vascular smooth muscle cells through modulation of interleukin-1. In Vitro Cell.Dev.Biol.-Animal 35, 647–654 (1999). https://doi.org/10.1007/s11626-999-0105-6

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