Novel TNF-α Receptor 1 Antagonist Treatment Attenuates Arterial Inflammation and Intimal Hyperplasia in Mice

• Kitagaki Manabu

  Medical Engineering, National Defense Medical College.

• Isoda Kikuo

  Internal Medicine I, National Defense Medical College.

• Kamada Haruhiko

  Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation.

• Kobayashi Takayuki

  Basic Pathology, National Defense Medical College.

• Tsunoda Shinichi

  Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation.

• Tsutsumi Yasuo

  Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation. Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University.

• Niida Tomiharu

  Internal Medicine I, National Defense Medical College.

• Kujiraoka Takehiko

  Internal Medicine I, National Defense Medical College.

• Ishigami Norio

  Internal Medicine I, National Defense Medical College.

• Ishihara Miya

  Medical Engineering, National Defense Medical College.

• Matsubara Osamu

  Basic Pathology, National Defense Medical College.

• Ohsuzu Fumitaka

  Internal Medicine I, National Defense Medical College.

• Kikuchi Makoto

  Medical Engineering, National Defense Medical College.

Abstract

Aim: Tumor necrosis factor receptor 1 (TNFR1) participates importantly in arterial inflammation in genetically altered mice; however it remains undetermined whether a selective TNFR1 antagonist inhibits arterial inflammation and intimal hyperplasia. This study aimed to determine the effect and mechanism of a novel TNFR1 antagonist in the suppression of arterial inflammation.<BR>Methods: We investigated intimal hyperplasia in IL-1 receptor antagonist-deficient mice two weeks after inducing femoral artery injury in an external vascular cuff model. All mice received intraperitoneal injections of TNFR1 antagonist (PEG-R1antTNF) or normal saline twice daily for 14 days.<BR>Results: PEG-R1antTNF treatment yielded no adverse systemic effects, and we observed no significant differences in serum cholesterol or blood pressure in either group; however, selective PEG-R1antTNF treatment significantly reduced intimal hyperplasia (19,671±4,274 vs. 11,440±3,292 µm²; p=0.001) and the intima/media ratio (1.86±0.43 vs. 1.34±0.36; p=0.029), compared with saline injection. Immunostaining revealed that PEG-R1antTNF inhibits Nuclear factor-κB (NF-κB), suppressing smooth muscle cell (SMC) proliferation and decreasing chemokine and adhesion molecule expression, and thus decreasing intimal hyperplasia and inflammation.<BR>Conclusions: Our data suggest that PEG-R1antTNF suppresses SMC proliferation and inflammation by inhibiting NF-κB. This study highlights the potential therapeutic benefit of selective TNFR1 antagonist therapy in preventing intimal hyperplasia and arterial inflammation.

Journal

• Journal of Atherosclerosis and Thrombosis

  Journal of Atherosclerosis and Thrombosis 19 (1), 36-46, 2012

  Japan Atherosclerosis Society

Keywords

• TNF receptor 1 antagonist
• Cytokine
• Inflammation
• Intimal hyperplasia
• Smooth muscle cell

Details

• CRID: 1390282679409852800
• NII Article ID: 130004721901
• DOI: 10.5551/jat.9746
• ISSN: 18803873
• ISSN: 13403478
• Web Site: https://search.jamas.or.jp/link/ui/2013123197
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed