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 mit ogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1 beta (IL-1 beta), which is p resent in atherosclerotic lesions, induces VEGF gene expression in vas cular smooth muscle cells, we performed RNA blot analysis on rat aorti c smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1 beta in creased 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 S-fol d and 10 ng/ml IL-1 beta increased VEGF mRNA by 4-fold. We also measur ed 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 len gthened 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 tha t 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 ves sels.