STAT3/NF-κB decoy oligodeoxynucleotides inhibit atherosclerosis through regulation of the STAT/NF-κB signaling pathway in a mouse model of atherosclerosis

Atherosclerosis is a progressive chronic inflammatory condition that is the cause of most cardiovascular and cerebrovascular diseases. The transcription factor nuclear factor-?B (NF-?B) regulates a number of genes involved in the inflammatory responses of cells that are critical to atherogenesis, and signal transducer and activator of transcription (STAT)3 is a key transcription factor in immunity and inflammation. Decoy oligodeoxynucleotides (ODNs) bind to sequence-specific transcription factors and limit gene expression by interfering with transcription in vitro and in vivo. The present study aimed to investigate the beneficial functions of STAT3/NF-?B decoy ODNs in liposaccharide (LPS)-induced atherosclerosis in mice. Atherosclerotic injuries of mice were induced via intraperitoneal injection of LPS and the mice were fed an atherogenic diet. Ring-type STAT3/NF-?B decoy ODNs were designed and administered via an injection into the tail vein of the mice. To investigate the effect of STAT3/NF-?B decoy ODNs, electrophoretic mobility shift assay, western blot analysis, histological analysis with hematoxylin and eosin staining, Verhoeff-Van Gieson and Masson's trichrome staining were performed. The results revealed that STAT3/NF-?B decoy ODNs were able to suppress the development of atherosclerosis by attenuating morphological changes and inflammation in atherosclerotic mice aortae, and by reducing pro-inflammatory cytokine secretion through inhibition of the STAT3/NF-?B pathway. In conclusion, the present study provided novel insights into the antiatherogenic molecular mechanism of STAT3/NF-?B decoy ODNs, which may serve as an additional therapeutic intervention to combat atherosclerosis.