Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells.
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1 beta (IL-1 beta), which is present in atherosclerotic lesions, induces VEGF gene expression in vascular smooth muscle cells, we performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1 beta increased VEGF mRNA levels in RASMC in a time- and dose-dependent manner. As little as 0.1 ng/ml IL-1 beta increased VEGF mRNA levels by 2-fold and 10 ng/ml IL-1 beta increased VEGF mRNA by 4-fold. We also measured the half-life of VEGF mRNA and performed nuclear run-on experiments before and after addition of IL-1 beta to see if IL-1 beta increased VEGF mRNA levels by stabilizing the mRNA or by increasing its rate of transcription. The normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1 beta, and IL-1 beta increased the rate of VEGF gene transcription by 2.1-fold. In immunoblot experiments with an antibody specific for VEGF, we found that IL-1 beta increased VEGF protein levels in RASMC by 3.3-fold. Together these data indicate that IL-1 beta induces VEGF gene expression in smooth muscle cells. This IL-1 beta-induced expression of VEGF may accelerate the progression of atherosclerotic lesions by promoting the development of new blood vessels.
Li
J
J
Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115.
Perrella
M A
MA
Tsai
J C
JC
Yet
S F
SF
Hsieh
C M
CM
Yoshizumi
M
M
Patterson
C
C
Endege
W O
WO
Zhou
F
F
Lee
M E
ME
D000818:Animals; D001011:Aorta; D001483:Base Sequence; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000494:pharmacology*; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007375:Interleukin-1; D008222:Lymphokines; D009838:Oligodeoxyribonucleotides; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors