Recombinant platelet-derived growth factor B gene expression in porcine arteries induce intimal hyperplasia in vivo.
Platelet-derived growth factor (PDGF) B chain induces cell proliferation in vitro and is associated with arterial lesions that cause cardiovascular disease. However, it has been difficult to document the biological response to PDGF B gene expression in arteries in vivo. To determine the biologic effects of this growth factor in vivo, we have introduced an eukaryotic expression vector plasmid encoding recombinant PDGF B by direct gene transfer into porcine iliofemoral arteries using DNA liposome complexes. The presence of PDGF B plasmid DNA and expression of recombinant mRNA were confirmed by polymerase chain reaction analysis, and recombinant PDGF protein was demonstrated by immunohistochemistry. Intimal thickening was observed in porcine arteries 21 days following transfection with the recombinant PDGF B gene compared with arteries transduced with a control gene, E. coli beta-galactosidase. An eightfold increase in intimal to medial ratio was present in PDGF B gene transfected arteries compared with control transfected arteries (P = 0.001). This study suggests that expression of a recombinant PDGF B gene in vivo can play a role in the induction of intimal hyperplasia, which can lead to cardiovascular diseases.
Nabel
E G
EG
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan, Ann Arbor 48109.
Yang
Z
Z
Liptay
S
S
San
H
H
Gordon
D
D
Haudenschild
C C
CC
Nabel
G J
GJ
D000818:Animals; D001158:Arteries / Q000473:pathology* / Q000502:physiology*; D001483:Base Sequence; D005263:Femoral Artery; D015870:Gene Expression; D006965:Hyperplasia / Q000139:chemically induced; D007083:Iliac Artery; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000235:genetics; D013552:Swine
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins