Effects of a stable prostacyclin analogue beraprost sodium on VEGF and PAI-1 gene expression in vascular smooth muscle cells.

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.

HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function).

We have been examining the role of heat shock factor 1 (HSF1) in the pleiotropic effects of statins. In parallel studies, we found that statin induces the nuclear translocation of HSF1 and that a decoy oligonucleotide encoding the heat shock element inhibits the statin-induced expression of heat shock protein 70, endothelial nitric oxide synthase (eNOS) and thrombomodulin. Also, in vascular endothelial cells, increases in the expression of human HSF1 corresponded with elevated steady-state levels of eNOS and thrombomodulin and reduced levels of endothelin-1 and plasminogen activator inhibitor-1.

Simvastatin induces heat shock factor 1 in vascular endothelial cells.

Statins not only reduce serum cholesterol but they also improve vascular endothelial function independent of their lipid-lowering effects. However, except for the mechanism of nitric oxide induction via calveolin, the physiologic basis for the pleiotropic effect of statins remains unknown. In the present study, we investigated the relationship between the effects of statins on vascular endothelial cell function and heat shock proteins.