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Enhancement by beraprost sodium, a stable analogue of prostacyclin, in thrombomodulin expression on membrane surface of cultured vascular endothelial cells via increase in cyclic AMP level

Authors
  • Kainoh, Mie
  • Maruyama, Ikuro
  • Nishio, Shintaro
  • Nakadate, Teruo
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 1991
Accepted Date
Nov 13, 1990
Volume
41
Issue
8
Pages
1135–1140
Identifiers
DOI: 10.1016/0006-2952(91)90651-K
Source
Elsevier
Keywords
License
Unknown

Abstract

Prostacyclin and beraprost sodium (beraprost), a stable analogue of prostacyclin, increased cyclic AMP (cAMP) levels of cultured human umbilical vein endothelial cells (HUVEC) in a concentration-dependent manner. The elevation of cAMP by beraprost was sustained longer than that by prostacyclin. The expression of thrombomodulin (TM) on membrane surface of HUVEC was enhanced by beraprost and prostacyclin, and the persistence of the increase in TM expression by beraprost was greater than prostacyclin. Dibutyryl cAMP (db-cAMP) mimicked the effects of beraprost and 3-isobutyl-1-methylxanthine enhanced the effects. Beraprost, prostacyclin and db-cAMP also effectively blocked the interleukin-1- and tumor necrosis factor-induced depression of TM expression substantially. These results suggest that TM expression is positively regulated by cAMP in HUVEC, and that beraprost may be potentially effective for reducing thrombotic events through the mechanism which initiates the stimulation of cAMP/TM system in vascular endothelial cells.

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