The IL-24 gene protects human umbilical vein endothelial cells against H2O2-induced injury and may be useful as a treatment for cardiovascular disease

摘要

The aim of the present study was to investigate the protective effects of interleukin-24?(IL-24) on hydrogen peroxide?(H2O2)-induced vascular endothelial injury and to examine the association between IL-24 and cardiovascular disease. Human umbilical vein endothelial cells?(HUVECs) were exposed to increasing concentrations of H2O2 in the presence or absence of IL-24, which was introduced via Lipofectamine??2000-mediated transfection. The successful uptake of the IL-24 plasmid was confirmed by RT-PCR at 24?h post-transfection. The effects of H2O2 and IL-24 on the proliferation and migration of the HUVECs was determined using cell migration assays. Cell viability was determined using a Cell Counting Kit-8?(CCK-8). Apoptosis and the measurement of the intracellular reactive oxygen species?(ROS) levels were determined by flow cytometry, and the levels of caspase-3, which is associated with apoptosis, were determined by western blot analysis. Real?time PCR and western blot analysis were also used to measure the levels of multiple cardiovascular disease?associated factors. In?vivo experiments were also performed using a rat model of hypertension which was constructed by angiotensin?II infusion using an osmotic pump. The mRNA and protein levels of IL-24 were measured in both the control and hypertensive rats; the effects of treatment with enalapril and nifedipine on the IL-24 levels were also examined. Our results revealed that IL-24 protected against the H2O2-mediated abnormal increase in HUVEC proliferation. IL-24 also antagonized H2O2 by reducing the content of ROS in the cells, thus decreasing cellular oxidative damage, improving the cellular survival rate, reducing apoptosis and decreasing the expression of cardiovascular disease-related factors. The results from our in?vivo animal experiments revealed that IL-24 expression was lower in the hypertensive rats compared to the healthy controls. Additionally, the IL-24 levels increased following anti-hypertensive therapy. The findings of our study indicate that IL-24 protects against H2O2-mediated endothelial cell damage and may thus provide a novel therapeutic strategy for treatment of cardiovascular disease.