RNA interference for HIF-1α inhibits foam cells formation in vitro

Macrophage-derived foam cells in atherosclerotic lesions are generally thought to play a major role in the pathology of the disease. Hypoxia-inducible factor-1 alpha (HIF-1 alpha) was recently found to play an important role in atherosclerosis. Here we applied RNA interference to study the role of HIF-1 alpha in foam cell fort-nation in vitro. Transfeclion of HIF-1 alpha-siRNA reduced HIF-1 alpha synthesis as measured on MRNA and protein level by real-time RT-PCR, Western blot. It was found that RNA interference for HIF-1 alpha with small interfering RNAs (HIF-1 alpha-siRNA) inhibits foam cell formation by the human monoblastic cell line (U937) which was treated with oxidized low-density lipoprotein (ox-LDL) while the majority of atherosclerosis-related genes, such as cyclooxygenase-2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 beta (IL-1 beta), and so on, were down-regulated, through large scale gene expression analysis using DNA microarrays. These data demonstrate that induction of HIF-1 alpha by atherogenic factors may be a key step in coordinating the cellular events that result in atherosclerotic lesions. (c) 2007 Elsevier B.V. All rights reserved.