Platelet-derived microparticles stimulate coronary artery smooth muscle cell mitogenesis by a PDGF-independent mechanism.
This study investigates the role of platelet-derived microparticles for vascular smooth muscle cell (SMC) proliferation. Microparticles concentration dependently stimulated p42/p44 MAP kinase phosphorylation, c-fos induction, DNA synthesis, and proliferation of cultured bovine coronary artery SMC. The maximum mitogenic effects of microparticles were significantly higher than those of platelet-derived growth factor (PDGF)-BB. Microparticle-induced SMC mitogenesis was heat sensitive, whereas the effects of PDGF were not. In addition, neutralizing anti-PDGF antibodies prevented PDGF-induced DNA synthesis but did not inhibit the effects of microparticles. In contrast to PDGF, which potently stimulated SMC migration, microparticles had only minor migratory activity. These results demonstrate a novel mechanism of SMC mitogenesis by platelet-derived microparticles that is probably independent of PDGF.
Weber
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Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
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D000818:Animals; D001792:Blood Platelets / Q000502:physiology / Q000648:ultrastructure*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D013347:Subcellular Fractions / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D010982:Platelet-Derived Growth Factor; D016760:Proto-Oncogene Proteins c-fos; D014316:Tritium; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013936:Thymidine