Platelet-derived growth factor-induced expression of c-fos in human vascular smooth muscle cells: implications for long-term graft patency.
BACKGROUND
The internal mammary artery (IMA) has been shown to have a significantly superior long-term patency rate when compared with the saphenous vein (SV) graft. Cultured smooth muscle cells (SMCs) from the IMA are more resistant to the mitogenic effects of platelet-derived growth factor (PDGF), when compared with SMCs that are derived from the SV. The radial artery (RA) is currently being used as an alternative to the SV. However, no long-term patency data are available for the RA, and there is no information on the biological behavior of RA-derived SMCs in culture.


METHODS
Smooth muscle cell cultures were taken from patients who underwent coronary artery bypass grafting with the IMA, RA, and SV. A quiescent state was induced by serum deprivation for 5 days. Thereafter cells were induced to proliferate by exposure to PDGF-BB. Levels of c-fos expression and 3H-thymidine incorporation were used as markers of cell proliferation.


RESULTS
We found that even after serum deprivation, c-fos was still detectable; however, basal levels were higher in cells from the SV than cells from either the RA (p = 0.003) or IMA (p = 0.008). After stimulation with PDGF-BB, c-fos expression was greater in SMCs from the SV relative to the RA (p < 0.001) or the IMA (p = 0.02). Finally, relative to the SV, 3H-thymidine in the RA was 0.76 +/- 0.22 (p < 0.05) and 0.39 +/- 0.24 (p < 0.002) in the IMA, respectively.


CONCLUSIONS
The data indicate that SMCs from arterial conduits are more resistant to the mitogenic effects of PDGF-BB than those from venous conduits. Our results offer a mechanistic explanation of why arterial conduits might demonstrate patency superior to that of the SV.
Del Rizzo
Dario F
DF
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, University of Manitoba, Faculty of Medicine, Winnipeg, Canada.
Yurkova
Natalia
N
Moon
Michael C
MC
Litchie
Brenda
B
Zahradka
Peter
P
D000368:Aged; D000077214:Becaplermin; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D001026:Coronary Artery Bypass; D015870:Gene Expression; D016762:Genes, fos / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis; D017534:Radial Artery / Q000502:physiology; D012501:Saphenous Vein / Q000502:physiology; D014654:Vascular Patency / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin