title: Stimulation of prostacyclin formation by the platelet-derived growth factor--an important pathomechanism for atherogenesis?
abstract: The capacity of vascular tissue in generating PGI2 has been accepted to be a key property in hemostatic balancing at a local level. Earlier it has been shown that PDGF is able to enhance SMC-proliferation. As this process is associated with c-AMP changes which again are influenced by PGI2, the question arose, whether PDGF itself exerts an effect on PGI2-synthesis. Using normal and atherosclerotic human arterial tissue, animal arteries and cultured cells with and without addition of various PDGF-concentrations this question was answered by means of bioassay and RIA-determination in a static and a pulsatile perfusion chamber system as well. In general, between 10 and 50 ng PDGF/ml, a significant increase either in PGI2-formation or 6-oxo-PGF1 alpha can be seen. A similar dose dependent stimulation of PGI2-synthesis can be monitored for vascular tissue and cultured cells as well. Static incubation and perfusion chamber experiments reveal comparable findings of PDGF stimulatory capacity on PGI2-formation. In contrast, no such effect can be seen using human umbilical artery. The half-life of PGI2-formation in the perfusion chamber model is comparable in presence and absence of PDGF as well. The stimulatory effect of PDGF on atherosclerotic vascular tissue is significantly less pronounced than onto normal one. Concluding from our findings we speculate that PGI2 prevents PDGF-release from platelets, thus decreasing smooth muscle cell proliferation and improving cellular lipid metabolism; an insufficient response of vascular tissue onto PDGF to generate PGI2 might be a key event in the pathogenesis of early atherosclerosis favouring a negative vicious cycle.
authors.affiliation: Atherosclerosis Research Group (ASF) Vienna, Austrian Academy of Sciences, Ludwig Boltzmann Institute for Nuclear Medicine, Vienna.
authors.forename: H
authors.initials: H
authors.lastname: Sinzinger
authors.forename: T
authors.initials: T
authors.lastname: Zidek
authors.forename: J
authors.initials: J
authors.lastname: Kalman
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine; D013556:Swine, Miniature
chemical_list: D010982:Platelet-Derived Growth Factor; D011464:Epoprostenol