Platelet surface membranes are highly mitogenic for coronary artery smooth muscle cells--A novel mechanism for sustained proliferation after vessel injury?
The effects of isolated platelet surface membranes on DNA synthesis and proliferation of bovine coronary artery smooth muscle cells (SMC) were studied. Platelet membranes were very potent mitogens for SMC. The potency was about 10-fold higher than the maximum effects of platelet-derived growth factor-BB (PDGF). Platelet membrane-induced mitogenesis was inhibited by rapamycin, wortmannin or heating for 15 min at 70 degrees C but not by the PDGF receptor antagonist SCH 13.929 or by neutralizing PDGF antibodies. Only a partial (30%) inhibition was seen with PD 98059. In contrast, PDGF-induced SMC mitogenesis was heat-stable but sensitive to SCH 13. 929, PDGF antibodies, and PD 98059. These findings provide evidence for a novel mechanism for platelet-induced SMC proliferation that is independent of PDGF secretion. Platelet membranes, attached to or incorporated into the vessel wall, could maintain sustained SMC proliferation following injury.
Weber
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Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Zucker
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Schrör
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D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000077214:Becaplermin; D001792:Blood Platelets / Q000378:metabolism*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002722:Chlorobenzenes / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology; D006358:Hot Temperature; D008934:Mitogens / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010797:Phthalimides / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D020123:Sirolimus / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D000906:Antibodies; D002722:Chlorobenzenes; D005419:Flavonoids; D008934:Mitogens; D010797:Phthalimides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C088156:2-bromomethyl-5-chlorobenzene sulfonylphthalimide; D000077214:Becaplermin; D004247:DNA; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus; D000077191:Wortmannin