The proliferative response to platelet-derived growth factor of smooth muscle cells isolated from synthetic vascular grafts in a canine model

Objective: Previous studies on graft healing have shown increased platelet- derived growth factor (PDGF) production in graft segments versus native aor tic segments. The purpose of this study was to characterize the proliferati ve response of graft smooth muscle cells (SMCs) to PDGF. Methods: Thoracoabdominal grafts were implanted in beagles. SMCs were harve sted from the graft and the proximal and distal aortas. Basal proliferation was assessed with growth curves in primary culture. The proliferative resp onse to PDGF then was compared with [H-3]thymidine uptake studies and cell counts. finally, PDGF receptors were characterized with radio-labeled ligan d binding assays. Results: The growth curves showed that the graft SMCs entered log-phase gro wth 2 days earlier than did the aortic SMCs. Stimulation of quiescent early -passage graft SMCs with PDGF (10 ng/ml;) resulted in a 1.7 +/- 0.1-fold in crease in [H-3]thymidine incorporation, which was significantly less than t hat of the SMCs fi om both the proximal aorta (11.8 +/- 3.0) and the distal aorta (10.2 +/- 1.9; P < .5). Similarly, the 1.1 +/- 0.1-fold increase in graft SMC cell number was significantly less than the increases for both pr oximal (2.8 +/- 0.5) and distal (2.9 +/- 0.8) aortic SMCs (P < .5). Binding studies on quiescent first-passage cells showed fewer PDGF receptors avail able for binding in the graft SMCs (185 +/- 70 fmol/million cells) as compa red with both the proximal (419 +/- 147 fmol/million cells) and the distal (387 +/- 112 fmol/million cells) aortas (P < .5). Binding affinity was simi lar for the three groups. Conclusion: Graft SMCs exist in a chronic proliferative state but exhibit a decreased proliferative response to PDGF and have fewer receptors availabl e for binding PDGF than do aortic SMCs in vitro.