The regulatory effect of norepinephrine on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) expression in cultured cardiac fibroblasts

BackgroundConnective tissue growth factor (CTGF) and vascular endothelial cell growth factor (VEGF) have been implicated as important effectors during cardiac remodeling. This study tested the hypothesis that norepinephrine (NE) induces CTGF and VEGF gene and protein expression in cardiac fibroblasts (CF) and the CTGF/VEGF complex will have an effect on angiogenesis.Methods and resultsRats CF were cultured in NE (0.01 to 100 μM) for 24 h. CTGF and VEGF gene expression were measured by quantitative-PCR. CTGF protein and CTGF/VEGF complex were detected by Western blot. The effect of CTGF/VEGF complex on angiogenesis was detected by endothelial cell tube formation assay. VEGF antigen level, reactive oxygen species (ROS) production were measured by ELISA and DCFH-DiOxyQ assay respectively. NE at 0.01 μM up-regulated CTGF mRNA and secretory protein expression significantly whereas at 100 μM both gene and protein were down-regulated significantly when compared with controls. At 0.01 to 0.1 μM of NE, there was no change in VEGF gene and protein level. NE at 100 μM increased VEGF gene and antigen level and ROS production significantly when compared with controls. CTGF/VEGF complex was found to inhibit the angiogenesis of endothelial cells.ConclusionsNE regulates CTGF and VEGF expression in a dose-dependent manner and via VEGF can induce angiogenesis. This work suggests NE may have an important role in ventricular remodeling.