Nanoparticle-mediated delivery of nuclear factor KB decoy into lungs ameliorates monocrotaline-induced pulmonary arterial hypertension

Satoshi Kimura, Kensuke Egashira, Ling Chen, Kaku Nakano, Eiko Iwata, Miho Miyagawa, Hiroyuki Tsujimoto, Kaori Hara, Ryuichi Morishita, Katsuo Sueishi, Ryuji Tominaga, Kenji Sunagawa

研究成果: ジャーナルへの寄稿記事

84 引用 (Scopus)

抄録

Pulmonary arterial hypertension (PAH) is an intractable disease of the small pulmonary artery that involves multiple inflammatory factors. We hypothesized that a redox-sensitive transcription factor, nuclear factor κB (NF-κB), which regulates important inflammatory cytokines, plays a pivotal role in PAH. We investigated the activity of NF-κB in explanted lungs from patients with PAH and in a rat model of PAH. We also examined a nanotechnology-based therapeutic intervention in the rat model. Immunohistochemistry results indicated that the activity of NF-κB increased in small pulmonary arterial lesions and alveolar macrophages in lungs from patients with PAH compared with lungs from control patients. In a rat model of monocrotaline-induced PAH, single intratracheal instillation of polymeric nanoparticles (NPs) resulted in delivery of NPs into lungs for ≤ 14 days postinstillation. The NP-mediated NF-κB decoy delivery into lungs prevented monocrotaline-induced NF-κB activation. Blockade of NF-κB by NP-mediated delivery of the NF-κB decoy attenuated inflammation and proliferation and, thus, attenuated the development of PAH and pulmonary arterial remodeling induced by monocrotaline. Treatment with the NF-κB decoy NP 3 weeks after monocrotaline injection improved the survival rale as compared with vehicle administration. In conclusion, these data suggest that NF-κB plays a primary role in the pathogenesis of PAH and, thus, represent a new target for therapeutic intervention in PAH. This nanotechnology platform may be developed as a novel molecular approach for treatment of PAH in the future.

元の言語英語
ページ(範囲)877-883
ページ数7
ジャーナルHypertension
53
発行部数5
DOI
出版物ステータス出版済み - 5 1 2009

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Monocrotaline
Pulmonary Hypertension
Nanoparticles
Lung
Nanotechnology
Respiratory Sounds
Alveolar Macrophages
Therapeutics
Pulmonary Artery
Oxidation-Reduction
Transcription Factors
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Internal Medicine

これを引用

Nanoparticle-mediated delivery of nuclear factor KB decoy into lungs ameliorates monocrotaline-induced pulmonary arterial hypertension. / Kimura, Satoshi; Egashira, Kensuke; Chen, Ling; Nakano, Kaku; Iwata, Eiko; Miyagawa, Miho; Tsujimoto, Hiroyuki; Hara, Kaori; Morishita, Ryuichi; Sueishi, Katsuo; Tominaga, Ryuji; Sunagawa, Kenji.

:: Hypertension, 巻 53, 番号 5, 01.05.2009, p. 877-883.

研究成果: ジャーナルへの寄稿記事

Kimura, S, Egashira, K, Chen, L, Nakano, K, Iwata, E, Miyagawa, M, Tsujimoto, H, Hara, K, Morishita, R, Sueishi, K, Tominaga, R & Sunagawa, K 2009, 'Nanoparticle-mediated delivery of nuclear factor KB decoy into lungs ameliorates monocrotaline-induced pulmonary arterial hypertension', Hypertension, 巻. 53, 番号 5, pp. 877-883. https://doi.org/10.1161/HYPERTENSIONAHA.108.121418
Kimura, Satoshi ; Egashira, Kensuke ; Chen, Ling ; Nakano, Kaku ; Iwata, Eiko ; Miyagawa, Miho ; Tsujimoto, Hiroyuki ; Hara, Kaori ; Morishita, Ryuichi ; Sueishi, Katsuo ; Tominaga, Ryuji ; Sunagawa, Kenji. / Nanoparticle-mediated delivery of nuclear factor KB decoy into lungs ameliorates monocrotaline-induced pulmonary arterial hypertension. :: Hypertension. 2009 ; 巻 53, 番号 5. pp. 877-883.
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abstract = "Pulmonary arterial hypertension (PAH) is an intractable disease of the small pulmonary artery that involves multiple inflammatory factors. We hypothesized that a redox-sensitive transcription factor, nuclear factor κB (NF-κB), which regulates important inflammatory cytokines, plays a pivotal role in PAH. We investigated the activity of NF-κB in explanted lungs from patients with PAH and in a rat model of PAH. We also examined a nanotechnology-based therapeutic intervention in the rat model. Immunohistochemistry results indicated that the activity of NF-κB increased in small pulmonary arterial lesions and alveolar macrophages in lungs from patients with PAH compared with lungs from control patients. In a rat model of monocrotaline-induced PAH, single intratracheal instillation of polymeric nanoparticles (NPs) resulted in delivery of NPs into lungs for ≤ 14 days postinstillation. The NP-mediated NF-κB decoy delivery into lungs prevented monocrotaline-induced NF-κB activation. Blockade of NF-κB by NP-mediated delivery of the NF-κB decoy attenuated inflammation and proliferation and, thus, attenuated the development of PAH and pulmonary arterial remodeling induced by monocrotaline. Treatment with the NF-κB decoy NP 3 weeks after monocrotaline injection improved the survival rale as compared with vehicle administration. In conclusion, these data suggest that NF-κB plays a primary role in the pathogenesis of PAH and, thus, represent a new target for therapeutic intervention in PAH. This nanotechnology platform may be developed as a novel molecular approach for treatment of PAH in the future.",
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AU - Nakano, Kaku

AU - Iwata, Eiko

AU - Miyagawa, Miho

AU - Tsujimoto, Hiroyuki

AU - Hara, Kaori

AU - Morishita, Ryuichi

AU - Sueishi, Katsuo

AU - Tominaga, Ryuji

AU - Sunagawa, Kenji

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