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 approximately 66% and the number of neointimal cells by approximately 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.
George
S J
SJ
Department of Cardiology, University of Wales College of Medicine, Cardiff, UK.
Williams
A
A
Newby
A C
AC
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division; D002465:Cell Movement; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012501:Saphenous Vein / Q000166:cytology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D007770:L-Lactate Dehydrogenase; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor