Nanoparticle-mediated delivery of pitavastatin into lungs ameliorates the development and induces regression of monocrotaline-induced pulmonary artery hypertension

Ling Chen, Kaku Nakano, Satoshi Kimura, Tetsuya Matoba, Eiko Iwata, Miho Miyagawa, Hiroyuki Tsujimoto, Kazuhiro Nagaoka, Junji Kishimoto, Kenji Sunagawa, Kensuke Egashira

研究成果: ジャーナルへの寄稿記事

57 引用 (Scopus)

抄録

Pulmonary artery hypertension (PAH) is an intractable disease of the small PAs in which multiple pathogenic factors are involved. Statins are known to mitigate endothelial injury and inhibit vascular remodeling and inflammation, all of which play crucial roles in the pathogenesis of PAH. We tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into the lungs can be a novel therapeutic approach for the treatment of PAH. Among the marketed statins, pitavastatin was found to have the most potent effects on proliferation of PA smooth muscle cells in vitro. We formulated pitavastatin-NP and found that pitavastatin-NP was more effective than pitavastatin alone in inhibiting cellular proliferation and inflammation in vitro. In a rat model of monocrotaline-induced PAH, a single intratracheal instillation of NP resulted in the delivery of NP into alveolar macrophages and small PAs for up to 14 days after instillation. Intratracheal treatment with pitavastatin-NP, but not with pitavastatin, attenuated the development of PAH and was associated with a reduction of inflammation and PA remodeling. NP-mediated pitavastatin delivery was more effective than systemic administration of pitavastatin in attenuating the development of PAH. Importantly, treatment with pitavastatin-NP 3 weeks after monocrotaline injection induced regression of PAH and improved survival rate. This mode of NP-mediated pitavastatin delivery into the lungs is effective in attenuating the development of PAH and inducing regression of established PAH, suggesting potential clinical significance for developing a new treatment for PAH.

元の言語英語
ページ(範囲)343-350
ページ数8
ジャーナルHypertension
57
発行部数2
DOI
出版物ステータス出版済み - 2 1 2011

Fingerprint

Monocrotaline
Pulmonary Hypertension
Nanoparticles
Pulmonary Artery
Lung
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Inflammation
pitavastatin
Therapeutics
Alveolar Macrophages
Smooth Muscle Myocytes

All Science Journal Classification (ASJC) codes

  • Internal Medicine

これを引用

Nanoparticle-mediated delivery of pitavastatin into lungs ameliorates the development and induces regression of monocrotaline-induced pulmonary artery hypertension. / Chen, Ling; Nakano, Kaku; Kimura, Satoshi; Matoba, Tetsuya; Iwata, Eiko; Miyagawa, Miho; Tsujimoto, Hiroyuki; Nagaoka, Kazuhiro; Kishimoto, Junji; Sunagawa, Kenji; Egashira, Kensuke.

:: Hypertension, 巻 57, 番号 2, 01.02.2011, p. 343-350.

研究成果: ジャーナルへの寄稿記事

@article{4a06b91f0fac4749bd85fff3d3823888,
title = "Nanoparticle-mediated delivery of pitavastatin into lungs ameliorates the development and induces regression of monocrotaline-induced pulmonary artery hypertension",
abstract = "Pulmonary artery hypertension (PAH) is an intractable disease of the small PAs in which multiple pathogenic factors are involved. Statins are known to mitigate endothelial injury and inhibit vascular remodeling and inflammation, all of which play crucial roles in the pathogenesis of PAH. We tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into the lungs can be a novel therapeutic approach for the treatment of PAH. Among the marketed statins, pitavastatin was found to have the most potent effects on proliferation of PA smooth muscle cells in vitro. We formulated pitavastatin-NP and found that pitavastatin-NP was more effective than pitavastatin alone in inhibiting cellular proliferation and inflammation in vitro. In a rat model of monocrotaline-induced PAH, a single intratracheal instillation of NP resulted in the delivery of NP into alveolar macrophages and small PAs for up to 14 days after instillation. Intratracheal treatment with pitavastatin-NP, but not with pitavastatin, attenuated the development of PAH and was associated with a reduction of inflammation and PA remodeling. NP-mediated pitavastatin delivery was more effective than systemic administration of pitavastatin in attenuating the development of PAH. Importantly, treatment with pitavastatin-NP 3 weeks after monocrotaline injection induced regression of PAH and improved survival rate. This mode of NP-mediated pitavastatin delivery into the lungs is effective in attenuating the development of PAH and inducing regression of established PAH, suggesting potential clinical significance for developing a new treatment for PAH.",
author = "Ling Chen and Kaku Nakano and Satoshi Kimura and Tetsuya Matoba and Eiko Iwata and Miho Miyagawa and Hiroyuki Tsujimoto and Kazuhiro Nagaoka and Junji Kishimoto and Kenji Sunagawa and Kensuke Egashira",
year = "2011",
month = "2",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.110.157032",
language = "English",
volume = "57",
pages = "343--350",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Nanoparticle-mediated delivery of pitavastatin into lungs ameliorates the development and induces regression of monocrotaline-induced pulmonary artery hypertension

AU - Chen, Ling

AU - Nakano, Kaku

AU - Kimura, Satoshi

AU - Matoba, Tetsuya

AU - Iwata, Eiko

AU - Miyagawa, Miho

AU - Tsujimoto, Hiroyuki

AU - Nagaoka, Kazuhiro

AU - Kishimoto, Junji

AU - Sunagawa, Kenji

AU - Egashira, Kensuke

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Pulmonary artery hypertension (PAH) is an intractable disease of the small PAs in which multiple pathogenic factors are involved. Statins are known to mitigate endothelial injury and inhibit vascular remodeling and inflammation, all of which play crucial roles in the pathogenesis of PAH. We tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into the lungs can be a novel therapeutic approach for the treatment of PAH. Among the marketed statins, pitavastatin was found to have the most potent effects on proliferation of PA smooth muscle cells in vitro. We formulated pitavastatin-NP and found that pitavastatin-NP was more effective than pitavastatin alone in inhibiting cellular proliferation and inflammation in vitro. In a rat model of monocrotaline-induced PAH, a single intratracheal instillation of NP resulted in the delivery of NP into alveolar macrophages and small PAs for up to 14 days after instillation. Intratracheal treatment with pitavastatin-NP, but not with pitavastatin, attenuated the development of PAH and was associated with a reduction of inflammation and PA remodeling. NP-mediated pitavastatin delivery was more effective than systemic administration of pitavastatin in attenuating the development of PAH. Importantly, treatment with pitavastatin-NP 3 weeks after monocrotaline injection induced regression of PAH and improved survival rate. This mode of NP-mediated pitavastatin delivery into the lungs is effective in attenuating the development of PAH and inducing regression of established PAH, suggesting potential clinical significance for developing a new treatment for PAH.

AB - Pulmonary artery hypertension (PAH) is an intractable disease of the small PAs in which multiple pathogenic factors are involved. Statins are known to mitigate endothelial injury and inhibit vascular remodeling and inflammation, all of which play crucial roles in the pathogenesis of PAH. We tested the hypothesis that nanoparticle (NP)-mediated delivery of pitavastatin into the lungs can be a novel therapeutic approach for the treatment of PAH. Among the marketed statins, pitavastatin was found to have the most potent effects on proliferation of PA smooth muscle cells in vitro. We formulated pitavastatin-NP and found that pitavastatin-NP was more effective than pitavastatin alone in inhibiting cellular proliferation and inflammation in vitro. In a rat model of monocrotaline-induced PAH, a single intratracheal instillation of NP resulted in the delivery of NP into alveolar macrophages and small PAs for up to 14 days after instillation. Intratracheal treatment with pitavastatin-NP, but not with pitavastatin, attenuated the development of PAH and was associated with a reduction of inflammation and PA remodeling. NP-mediated pitavastatin delivery was more effective than systemic administration of pitavastatin in attenuating the development of PAH. Importantly, treatment with pitavastatin-NP 3 weeks after monocrotaline injection induced regression of PAH and improved survival rate. This mode of NP-mediated pitavastatin delivery into the lungs is effective in attenuating the development of PAH and inducing regression of established PAH, suggesting potential clinical significance for developing a new treatment for PAH.

UR - http://www.scopus.com/inward/record.url?scp=79551471958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551471958&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.110.157032

DO - 10.1161/HYPERTENSIONAHA.110.157032

M3 - Article

C2 - 21220711

AN - SCOPUS:79551471958

VL - 57

SP - 343

EP - 350

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 2

ER -