Antimitogenic effects of vasodilatory prostaglandins in coronary artery smooth muscle cells.
Vasodilatory prostaglandins (PGI2, PGE2, PGE1) are known inhibitors of proliferation of vascular smooth muscle cells (SMC) after stimulation with mitogenic factors. However, endogenous prostaglandins do not prevent SMC proliferation subsequent to vessel injury in vivo. Since vascular cells produce large amounts of antiproliferative prostaglandins, especially subsequent to COX-2 expression, insufficient vascular PGI2 formation is not likely to explain the failure of endogenous prostaglandins to prevent excessive SMC growth. In this paper we demonstrate a rapid development of tolerance to PGI2 in SMC, resulting in diminished antiproliferative activity. These findings may not only be relevant for the control of SMC growth by endogenously synthesized prostaglandins but also for clinical use of PGI2 mimetics.
Weber
A A
AA
Institut für Pharmakologie Heinrich-Heine-Universität, Düsseldorf, Germany.
Zucker
T P
TP
Hasse
A
A
Bönisch
D
D
Wittpoth
M
M
Schrör
K
K
D000818:Animals; D000077214:Becaplermin; D002455:Cell Division; D003331:Coronary Vessels / Q000166:cytology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D014664:Vasodilation
D010982:Platelet-Derived Growth Factor; D011453:Prostaglandins; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin