Serum starvation and growth factor receptor expression in vascular smooth muscle cells.
BACKGROUND
Smooth muscle cell (SMC) proliferation in atherosclerosis is regulated through the interaction of growth factors like platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF-1) and their receptors (R). We hypothesized that serum starvation of SMCs may affect PDGFbeta-R and IGF-1-R expression and, consequently, the effect of their cognate ligands on SMC survival/proliferation.


RESULTS
Serum starvation significantly increases PDGFbeta-R but not IGF-1-R mRNA and protein expression in SMCs. PDGF-BB stimulates cell survival but not proliferation in serum-starved SMCs of the synthetic phenotype, whereas SMCs of the contractile phenotype respond to PDGF-BB by a significant increase in proliferation. Immunohistochemical analysis of coronary atherosclerotic lesions reveals PDGFbeta-R expression in SMCs in the lamina fibromuscularis, but not in the media and in healthy parts of the arterial wall. No such differential expression was observed for IGF-1-R.


CONCLUSIONS
Differential regulation of PDGFbeta-R and IGF-1-R expression by serum starvation might represent a mechanism for the control of SMC survival/proliferation in atherogenesis and restenosis. The distribution of PDGFbeta-Rs and IGF-1-Rs in atherosclerotic lesions may indicate an effect of serum starvation on SMCs in the arterial wall.
Zimmermann
Oliver
O
Center for Cell and Gene Therapy, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tex., USA. oliver.zimmermann@medizin.uni-ulm.de
Zwaka
Thomas P
TP
Marx
Nikolaus
N
Torzewski
Michael
M
Bucher
Andrea
A
Guilliard
Peter
P
Hannekum
Andreas
A
Hombach
Vinzenz
V
Torzewski
Jan
J
D000077214:Becaplermin; D049109:Cell Proliferation; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology; D016895:Culture Media, Serum-Free; D015536:Down-Regulation; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis*; D015854:Up-Regulation
D016895:Culture Media, Serum-Free; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D017526:Receptor, IGF Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta