Roles of vasodilatory prostaglandins in mitogenesis of vascular smooth muscle cells.
Vasodilatory prostaglandins (PGI2, PGE1) and synthetic prostacyclin mimetics inhibit smooth muscle cell proliferation in vitro after stimulation by growth factors. Similar results are obtained in vivo after endothelial injury, suggesting that vasodilatory prostaglandins might also control smooth muscle cell proliferation in vivo. However, available data from clinical trials are conflicting and currently do not support the concept that these compounds might be successfully used to suppress excessive smooth muscle cell growth in response to tissue injury, specifically restenosis after PTCA. One possible explanation for these different results is an agonist-induced down-regulation of prostacyclin receptors in vascular smooth muscle cells. It is possible that enhanced endogenous prostacyclin biosynthesis, subsequent to induction of COX-2 and/or in relation to the formation of a neointima from media smooth muscle cells, might have a similar effect. There is still uncertainty regarding the cellular signal transduction pathways and their possibly complex interaction, although cAMP-dependent reactions are probably involved. In addition, vasodilatory prostaglandins might also interfere with the generation and action of other growth modulating factors, including PDGF, hepatocyte growth factor and nitric oxide. In conclusion, vasodilatory prostaglandins might be considered as growth modulating endogenous mediators in vascular smooth muscle cells.
Schrör
K
K
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany. schroer@pharma.uni-duesseldorf.de
Weber
A A
AA
D000527:Alprostadil / Q000378:metabolism* / Q000494:pharmacology; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
D011464:Epoprostenol; D000527:Alprostadil