Aspirin enhances platelet-derived growth factor-induced vascular smooth muscle cell proliferation.
OBJECTIVE
Aspirin is frequently used after vascular reconstruction to pharmacologically prevent graft occlusion and to suppress the development of myointimal hyperplasia in vascular surgery, but its efficacy is controversial. The purpose of this study was to examine the direct effects of aspirin on platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell (SMC) proliferation.


METHODS
Human aortic SMCs were grown to confluence in 96 well plates. 3 x 10(-5) mol/L aspirin was added 24 hours previously and PDGF 10 ng/ml at the beginning of each experiment. Cell proliferation at 48 hours was determined using tritiated thymidine uptake. Supernatant 12-L-hydroxy 5,8,10,14-eicosatetraenoic acid (12-HETE) and prostaglandin E2 (PGE2) were measured by competitive enzyme immunoassay.


RESULTS
Aspirin did not change vascular SMC proliferation rates relative to controls (4665 +/- 181 counts per minute [CPM] vs 4749 +/- 155 CPM). However, aspirin pretreatment of PDGF-stimulated vascular SMCs increased proliferation (9408 +/- 237 CPM vs 7283 +/- 283 CPM; p < 0.001). 5,8,10,14-eicosatriynoic acid, a 12-lipoxygenase inhibitor, decreased basal (2037 +/- 181 CPM vs 2306 +/- 158 CPM; p < 0.05) and PDGF-stimulated vascular SMC proliferation (4909 +/- 1089 CPM vs 4310 +/- 1022 CPM; p < 0.001). Aspirin increased supernatant 12-HETE levels and decreased PGE2 levels in both basal and PDGF-stimulated cell cultures.


CONCLUSIONS
Aspirin enhances PDGF-stimulated vascular SMC proliferation. The effects of aspirin on vascular SMC proliferation may be mediated by changes in vascular SMC arachidonic acid metabolism.
Harvey
R
R
Department of Surgery, Maine Medical Center, Portland 04102, USA.
Bredenberg
C E
CE
Couper
L
L
Himmelfarb
J
J
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000032:analysis / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D004357:Drug Synergism; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D006965:Hyperplasia; D015999:Multivariate Analysis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012044:Regression Analysis; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014656:Vascular Surgical Procedures
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D014316:Tritium; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase; D015232:Dinoprostone; D001241:Aspirin; D013936:Thymidine