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

An,Hyun-Jin; Gwon,Mi-Gyeong; Gu,Hyemin; Bae,Seongjae; Leem,Jaechan; Lee,Jin Bae; Park,Kwan-Kyu

doi:10.3892/ijmm.2023.5240

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

Authors:
- Hyun-Jin An
- Mi-Gyeong Gwon
- Hyemin Gu
- Seongjae Bae
- Jaechan Leem
- Jin Bae Lee
- Kwan-Kyu Park
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Affiliations: Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea, Department of Immunology, College of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea, Department of Cardiology, Daegu Catholic University Medical Center, Daegu 42472, Republic of Korea
Published online on: March 31, 2023 https://doi.org/10.3892/ijmm.2023.5240
Article Number: 37
Copyright: © An et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis is a progressive chronic inflammatory condition that is the cause of most cardiovascular and cerebrovascular diseases. The transcription factor nuclear factor‑κB (NF‑κB) 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‑κB 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‑κB decoy ODNs were designed and administered via an injection into the tail vein of the mice. To investigate the effect of STAT3/NF‑κB 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‑κB 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‑κB pathway. In conclusion, the present study provided novel insights into the antiatherogenic molecular mechanism of STAT3/NF‑κB decoy ODNs, which may serve as an additional therapeutic intervention to combat atherosclerosis.

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