Regional differences in platelet-derived growth factor production by the canine aorta.

Abstract

Platelet-derived growth factor (PDGF) is a potent mitogen and chemotactic agent which may be involved in the formation of proliferative lesions of the arterial system, such as intimal hyperplasia and atherosclerosis. To examine the regional variation in vessel wall production of this mitogen, PDGF production and PDGF A chain mRNA expression by normal arterial wall was studied as a function of vessel location. PDGF production by canine aortic segments was measured after 72 h in organ culture, revealing significantly more PDGF produced by the distal compared to proximal aorta at 77 +/- 10 versus 14 +/- 6 pg/cm2/72 h (p<0.05). Endothelial cells (EC) and smooth muscle cells (SMC), isolated from analogous aortic sites, were grown in tissue culture and the conditioned medium was assayed for PDGF. EC in vitro demonstrated a similar geographic trend in PDGF production (distal=1,501 +/- 389 pg/microgram DNA/72 h, proximal=759 +/- 230 pg/microgram DNA/72 h; p=0.17). PDGF production by SMC in cell culture had a similar pattern with cells from the distal aorta producing 58 +/- 28 pg PDGF/microgram DNA/72 h, compared to cells from the proximal aorta producing 37 +/- 15 pg PDGF/microgram DNA/72 h (p=0.13). Freshly harvested EC and SMC, isolated from the same aortic sites, were subjected to quantitation of PDGF mRNA levels using a coupled reverse transcriptase and polymerase chain reaction amplification method, with glyceraldehyde-phosphate dehydrogenase (GAPDH) as a control. 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 canine aorta. Additionally, SMC are implicated as a significant contributor to the regional variation in PDGF production.