RNA interference for HIF-1alpha 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-1alpha (HIF-1alpha) was recently found to play an important role in atherosclerosis. Here we applied RNA interference to study the role of HIF-1alpha in foam cell formation in vitro. Transfection of HIF-1alpha-siRNA reduced HIF-1alpha synthesis as measured on mRNA and protein level by real-time RT-PCR, Western blot. It was found that RNA interference for HIF-1alpha with small interfering RNAs (HIF-1alpha-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-1beta (IL-1beta), and so on, were down-regulated, through large scale gene expression analysis using DNA microarrays. These data demonstrate that induction of HIF-1alpha by atherogenic factors may be a key step in coordinating the cellular events that result in atherosclerotic lesions.
Jiang
Guojun
G
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, China.
Li
Tiejun
T
Qiu
Yan
Y
Rui
Yaocheng
Y
Chen
Wansheng
W
Lou
Yijia
Y
D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D008077:Lipoproteins, LDL; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein