ASPIRIN ENHANCES PLATELET-DERIVED GROWTH FACTOR-INDUCED VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION

Purpose: Aspirin is frequently used after vascular reconstruction to p harmacologically prevent graft occlusion and to suppress the developme nt of myointimal hyperplasia in vascular surgery, but its efficacy is controversial. The purpose of this study was to examine the direct eff ects of aspirin on platelet-derived growth factor (PDGF)-induced vascu lar 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 ea ch experiment. Cell proliferation at 48 hours was determined using tri tiated thymidine uptake. Supernatant 12-L-hydroxy 5,8,10,14-eicosatetr aenoic acid (12-HETE) and prostaglandin E-2 (PGE(2)) were measured by competitive enzyme immunoassay. Results: Aspirin did not change vascul ar SMC proliferation rates relative to controls (4665 +/-a 181 counts per minute [CPM] vs 4749 +/- 155 CPM). However, aspirin pretreatment o f 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 (49 09 +/- 1089 CPM vs 4310 +/- 1022 CPM; p < 0.001). Aspirin increased su pernatant 12-HETE levels and decreased PGE(2) levels in both basal and PDGF-stimulated cell cultures. Conclusions: Aspirin enhances PDGF-sti mulated vascular SMC proliferation. The effects of aspirin on vascular SMC proliferation may be mediated by changes in vascular SMC arachido nic acid metabolism.