REGIONAL DIFFERENCES IN PLATELET-DERIVED GROWTH-FACTOR PRODUCTION BY THE CANINE AORTA

Platelet-derived growth factor (PDGF) is a potent mitogen and chemotac tic agent which may be involved in the formation of proliferative lesi ons of the arterial system, such as intimal hyperplasia and atheroscle rosis. To examine the regional variation in vessel wall production of this mitogen, PDGF production and PDGF A chain mRNA expression by norm al arterial wall was studied as a function of vessel location. PDGF pr oduction by canine aortic segments was measured after 72 h in organ cu lture, revealing significantly more PDGF produced by the distal compar ed to proximal aorta at 77 +/- 10 versus 14 +/- 6 pg/cm(2)/72 h (p < 0 .05). Endothelial cells (EC) and smooth muscle cells (SMC), isolated f rom analogous aortic sites, were grown in tissue culture and the condi tioned medium was assayed for PDGF. EC in vitro demonstrated a similar geographic trend in PDGF production (distal = 1,501 +/- 389 pg/mu g D NA/72 h, proximal = 759 +/- 230 pg/mu g DNA/72 h; p = 0.17). PDGF prod uction by SMC in cell culture had a similar pattern with cells from th e distal aorta producing 58 +/- 28 pg PDGF/mu g DNA/72 h, compared to cells from the proximal aorta producing 37 +/- 15 pg PDGF/mu g DNA/72 h (p = 0.13). Freshly harvested EC and SMC, isolated from the same aor tic sites, were subjected to quantitation of PDGF mRNA levels using a coupled reverse transcriptase and polymerase chain reaction amplificat ion method, with glyceraldehyde-phosphate dehydrogenase (GAPDH) as a c ontrol. The ratio of PDGF A chain:GAPDH mRNA was significantly greater in distal aortic SMC, 2.30 +/- 0.99, compared to proximal aortic SMC, 1.27 +/- 0.46 (p = 0.05), but was not significantly different between proximal and distal aortic EC (p = 0.86). These findings demonstrate significant regional differences in PDGF production in the normal cani ne aorta. Additionally, SMC are implicated as a significant contributo r to the regional variation in PDGF production.