Implications for Ischemic Tissues and Hypoxia-Regulated Gene Therapy

摘要: Macrophages accumulate in ischemic areas of such pathological tissues as solid tumors, atherosclerotic plaques and arthritic joints. Studies have suggested that hypoxia alters the phenotype macrophages a way promotes these lesions. However, genes up-regulated by hypoxic are poorly characterized. Here, we used cDNA array hybridization to investigate effects on mRNAs 1185 primary human monocyte-derived macrophages. As shown previously other cell types, mRNA levels for vascu- lar endothelial growth factor (VEGF) glucose transporter 1 (GLUT-1) were hypoxia. also up- regulated including matrix metalloproteinase-7 (MMP-7), neuromedin B receptor, DNA-bind- ing protein inhibitor, Id2. The promoters GLUT-1 MMP-7 confer inducibility reporter gene RAW 264.7 macrophages, indicating up-regulation may occur, at least part, transcriptional level. be vitro real-time RT-PCR, proteins elevated macro- phages breast tumors. identified could important survival functioning diseased tissues, their prove useful macrophage-deliv- ered therapy. (Am J Pathol 2003, 163:1233-1243)