Platelet-induced vascular smooth muscle cell proliferation is modulated by the growth amplification factors serotonin and adenosine diphosphate.
BACKGROUND
Platelet-mediated mechanisms have been implicated in intimal lesion formation following vascular injury. Although the participation of peptide growth factors has been suspected in this process, little has been known about the possible mitogenic role of other platelet factors that are released at sites of vascular injury.


RESULTS
We tested the hypothesis that platelet products, which are not peptide growth factors, are important modulators of the platelet-induced smooth muscle cell (SMC) proliferative response by acting as growth amplification factors. In these studies, cell proliferation was assessed by [3H]thymidine incorporation, flow cytometry, and direct cell counting. We examined the potential mitogenicity of several platelet products, including serotonin, ADP, norepinephrine, histamine, platelet-activating factor, the thromboxane A2 mimetic U46619, and bradykinin. Of the platelet products tested, serotonin and ADP induced a synergistic response with peptide growth factors. This synergy was greatest at low growth-factor concentrations. Addition of nonaggregated platelets to quiescent SMC cultures strongly stimulated cell proliferation. Since the addition of suramin to platelet-treated cultures markedly inhibited SMC proliferation, peptide growth factors are most likely the primary mitogens mediating this response. However, platelet-induced proliferation was also markedly reduced by the serotonin antagonists ketanserin and LY53857 (44%), and by the ADP antagonist apyrase (35%).


CONCLUSIONS
Therefore, serotonin and ADP contribute significantly, in synergy with peptide growth factors, to the platelet-induced SMC proliferative response. We propose that in vivo serotonin and ADP act as amplification factors for SMC proliferation at sites of vascular injury.
Crowley
S T
ST
Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262.
Dempsey
E C
EC
Horwitz
K B
KB
Horwitz
L D
LD
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010455:Peptides / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*
D006133:Growth Substances; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D012701:Serotonin; D000244:Adenosine Diphosphate; D004815:Epidermal Growth Factor