TY - JOUR
T1 - Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells
AU - Stavri, George T.
AU - Hong, Ying
AU - Zachary, Ian C.
AU - Breier, Georg
AU - Baskerville, Paul A.
AU - Ylä-Herttuala, Seppo
AU - Risau, Werner
AU - Martin, John F.
AU - Erusalimsky, Jorge D.
PY - 1995/1/30
Y1 - 1995/1/30
N2 - Vascular endothelial growth factor (VEGF) mRNA expression was analysed in rabbit vascular smooth muscle cells following exposure to hypoxia and platelet-derived growth factor-BB (PDGF-BB). Hypoxia potently upregulated VEGF mRNA steady-state levels in a time- and concentration-dependent manner reaching a maximum level (∼30-fold increase) after 12-24 h at 0% 02. In contrast, PDGF-BB caused a modest increase in VEGF expression. However, the combination of PDGF-BB and a threshold hypoxic stimulus (2.5% O2 for 4 h) had a marked synergistic effect. Synergy between hypoxia and PDGF-BB was selective for VEGF expression as hypoxia had no effect on the PDGF-induced upregulation of the proto-oncogene c-myc. These results raise the possibility that hypoxia and PDGF-BB may act in concert to induce VEGF expression in the arterial wall during the development of atherosclerosis.
AB - Vascular endothelial growth factor (VEGF) mRNA expression was analysed in rabbit vascular smooth muscle cells following exposure to hypoxia and platelet-derived growth factor-BB (PDGF-BB). Hypoxia potently upregulated VEGF mRNA steady-state levels in a time- and concentration-dependent manner reaching a maximum level (∼30-fold increase) after 12-24 h at 0% 02. In contrast, PDGF-BB caused a modest increase in VEGF expression. However, the combination of PDGF-BB and a threshold hypoxic stimulus (2.5% O2 for 4 h) had a marked synergistic effect. Synergy between hypoxia and PDGF-BB was selective for VEGF expression as hypoxia had no effect on the PDGF-induced upregulation of the proto-oncogene c-myc. These results raise the possibility that hypoxia and PDGF-BB may act in concert to induce VEGF expression in the arterial wall during the development of atherosclerosis.
KW - Atherosclerosis
KW - Hypoxia
KW - Platelet-derived growth factor
KW - Vascular endothelial growth factor
KW - Vascular smooth muscle cell
UR - http://www.scopus.com/inward/record.url?scp=0028950194&partnerID=8YFLogxK
U2 - 10.1016/0014-5793(94)01458-D
DO - 10.1016/0014-5793(94)01458-D
M3 - Article
C2 - 7843420
AN - SCOPUS:0028950194
SN - 0014-5793
VL - 358
SP - 311
EP - 315
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -