An essential role for platelet-derived growth factor in neointima formation in human saphenous vein in vitro

The role of platelet-derived growth factor (PDGF), a potent vascular smooth muscle cells (SMC) mitogen and chemoattractant, was investigated during neointima formation in human saphenous vein organ culture. PDGFA and B messenger ribonucleic acid (mRNA) expression was detected by RNase protection assay and in situ hybridisation and PDGF protein by immunocytochemistry. The expression of PDGFA and B mRNA was low in veins before culture while PDGF protein was detected in all cell types. A neointima consisting of densely packed SMC developed after 14 days of culture. The dense packing and high expression of PDGFA and B mRNA in neointimal SMC led to higher PDGF protein concentrations in the neointima, the role of which was examined by culturing with neutralising anti-(human PDGF) antibodies. The anti-PDGF antibodies significantly reduced neointimal thickness by ˜ 66% and the number of neointimal cells by ˜ 50%, without affecting neointimal or medial proliferation indices or cell viability. These results suggest that PDGF played an essential role in SMC migration into the neointima in human saphenous vein.