Antimitotic actions of vasodilatory prostaglandins--clinical aspects.
A variety of in-vitro antiatherosclerotic actions, among them those on vascular smooth muscle cells (mitotic activity, proliferation, extracellular matrix production), have been identified especially for PGE1 and PGI2, and proven in experimental animals. Ex-vivo data in humans are not yet available. We examined the effect of PGE1-, PGI2- and iloprost therapy of various duration (1-4 weeks) on smooth muscle cells (mitosis, proliferation, prostaglandin formation from exogenous and endogenous substrate) derived from vascular surgery samples. In-vivo PG-therapy decreases [3H]-thymidine incorporation as well as [35]S- and [14C]-proline uptake. These effects are dependent on the duration of treatment, PGE1 being trendwise more effective. Arachidonic acid conversion to PGI2 is significantly enhanced in activated smooth muscle cells of the plaque, both in the intima as well as in the media. Due to the activation of the gene for COX-2, the actual synthesis of PGI2 as well as the conversion rate to 6-oxo-PGF1 alpha are increased in activated smooth muscle cells, an effect being abolished by the PG's administered. It can thus be concluded that PG-therapy for advanced atherosclerosis seems to affect vascular smooth muscle cells beneficially, decreasing mitotic and proliferative activity as well as collagen and glycosaminoglycan synthesis. The somewhat less pronounced effect for PGI2 and iloprost could be explained by desensitization at the receptor level as preliminary findings suggest. This could become even more relevant if a long-term administrable stable (oral) analogue becomes available for routine therapy.
Sinzinger
H
H
Wilhelm Auerswald Atherosclerosis Research Group (ASF), Vienna, Austria.
Fitscha
P
P
Kritz
H
H
D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000494:pharmacology / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D011464:Epoprostenol / Q000494:pharmacology / Q000627:therapeutic use*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D006025:Glycosaminoglycans; D003094:Collagen; D011464:Epoprostenol; D000527:Alprostadil