These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Effects of a stable prostacyclin analogue beraprost sodium on VEGF and PAI-1 gene expression in vascular smooth muscle cells.
    Author: Atsuta H, Uchiyama T, Kanai H, Iso T, Tanaka T, Suga T, Maeno T, Arai M, Nagai R, Kurabayashi M.
    Journal: Int J Cardiol; 2009 Mar 06; 132(3):411-8. PubMed ID: 18471910.
    Abstract:
    BACKGROUND: Beraprost sodium, an orally active prostacyclin analogue, has proved to be beneficial for the patients with primary pulmonary hypertension and obstructive peripheral arterial disease. METHODS: In this study, we examined the effects of BPS on the expression of the VEGF and PAI-1 genes in vascular smooth muscle cells. RESULTS: The mRNA levels for VEGF were increased by BPS in C2/2 cells and cultured rat aortic smooth muscle cells. In contrast, PAI-1 mRNA levels were significantly decreased by BPS. Luciferase assays and mRNA decay assays showed that BPS increases VEGF promoter activity and has no effects on its mRNA stability. Likewise, BPS decreases PAI-1 promoter activity without affecting its mRNA stability. Experiments using various pharmacological inhibitors for protein kinases showed that activation of cAMP-dependent protein kinase (PKA) was involved in BPS-mediated regulation of VEGF and PAI-1 mRNA expression. Overexpression of CREB (cAMP-responsive element binding protein) induces VEGF promoter and reduces PAI-1 promoter activities. CREMepsilon, a dominant negative form of CREB, inhibits BPS-mediated changes in VEGF and PAI-1 promoter activities. While BPS augmented hypoxia-induced VEGF mRNA expression, it blunted hypoxia-induced PAI-1 mRNA expression. CONCLUSION: These results suggest that BPS increases VEGF and decreases PAI-1 gene expression through PKA/CREB-dependent mechanisms in vascular smooth muscle cells. Because these effects are observed more prominently under the hypoxic condition compared to normoxic condition, BPS may have a potential to relieve hypoxia by inducing neovasculization and by reducing thrombosis.
    [Abstract] [Full Text] [Related] [New Search]