Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Aged
-
Antibodies, Monoclonal / pharmacology
-
Base Sequence
-
Cell Division
-
Cell Movement
-
Female
-
Humans
-
In Situ Hybridization
-
L-Lactate Dehydrogenase / analysis
-
Male
-
Middle Aged
-
Molecular Sequence Data
-
Muscle, Smooth, Vascular / cytology
-
Muscle, Smooth, Vascular / metabolism*
-
Organ Culture Techniques
-
Platelet-Derived Growth Factor / biosynthesis
-
Platelet-Derived Growth Factor / genetics
-
Platelet-Derived Growth Factor / immunology
-
Platelet-Derived Growth Factor / physiology*
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / physiology*
-
Proto-Oncogene Proteins c-sis
-
RNA, Messenger / biosynthesis
-
Receptor, Platelet-Derived Growth Factor alpha
-
Receptors, Platelet-Derived Growth Factor / biosynthesis
-
Receptors, Platelet-Derived Growth Factor / genetics
-
Receptors, Platelet-Derived Growth Factor / physiology*
-
Saphenous Vein / cytology
-
Saphenous Vein / metabolism*
Substances
-
Antibodies, Monoclonal
-
Platelet-Derived Growth Factor
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-sis
-
RNA, Messenger
-
platelet-derived growth factor A
-
L-Lactate Dehydrogenase
-
Receptor, Platelet-Derived Growth Factor alpha
-
Receptors, Platelet-Derived Growth Factor