Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model

Kai Liu,1 Xiquan Zhang,1 Guangqing Cao,1 Yongjun Liu,2 Chuanzhen Liu,1 Hourong Sun,1 Xinyan Pang1 1Cardiovascular Surgery Department, Qilu Hospital of Shandong University, 2Pharmacy College of Shandong University, Jinan, People’s Republic of China Purpose: To investigate whether inhalati...

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Autores principales: Liu K, Zhang XQ, Cao GQ, Liu YJ, Liu CZ, Sun HR, Pang XY
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Publicado: Dove Medical Press 2016
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spelling oai:doaj.org-article:7c9c8fa7f6e649ed8fc5bdee67bb431f2021-12-02T04:28:15ZIntratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model1178-2013https://doaj.org/article/7c9c8fa7f6e649ed8fc5bdee67bb431f2016-06-01T00:00:00Zhttps://www.dovepress.com/intratracheal-instillation-of-ethyl-pyruvate-nanoparticles-prevents-th-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kai Liu,1 Xiquan Zhang,1 Guangqing Cao,1 Yongjun Liu,2 Chuanzhen Liu,1 Hourong Sun,1 Xinyan Pang1 1Cardiovascular Surgery Department, Qilu Hospital of Shandong University, 2Pharmacy College of Shandong University, Jinan, People’s Republic of China Purpose: To investigate whether inhalation of ethyl pyruvate (EP) encapsulated with poly(ethylene glycol)-block-lactide/glycolide copolymer nanoparticles (EP-NPs) can prevent the development of shunt-flow-induced hyperkinetic pulmonary arterial hypertension (PAH) in a rat model.Materials and methods: Rats were separated into five groups: blank (ie, no treatment after shunt flow), normal control (ie, no shunt flow or treatment), EP-NP instillation, EP-only instillation, and vehicle. The animals received intratracheal instillation of EP-NPs or other treatments immediately after a shunt flow, and treatment continued weekly until the end of the experiment. Hemodynamic data were recorded, pulmonary arterial remodeling was assessed, and levels of inflammatory mediators and ET1 expression in the lung and serum were analyzed. In addition, retention of EP in the lungs of rats in the EP-NP and EP-only groups was measured using high-performance liquid chromatography.Results: After 12 weeks, hemodynamic abnormalities and pulmonary arterial remodeling were improved in the EP-NP instillation group, compared with the blank, EP-only, and vehicle groups (P<0.05). In addition, the EP-NP group showed significantly decreased levels of HMGB1, IL-6, TNFα, reactive oxygen species, and ET1 in the lung during PAH development (P<0.05). Furthermore, EP-NP instillation was associated with reduced serum levels of inflammatory factors and ET1. High-performance liquid-chromatography measurement indicated that EP retention was greater in the lungs of the EP-NP group than in the EP-only group.Conclusion: EP-NP instillation attenuated inflammation and prevented pulmonary arterial remodeling during the development of PAH induced by shunt flow. In the future, EP-NP delivery into the lung might provide a novel approach for preventing PAH. Keywords: pulmonary artery hypertension, ethyl pyruvate, high-mobility group box 1Liu KZhang XQCao GQLiu YJLiu CZSun HRPang XYDove Medical PressarticlePulmonary artery hypertensionethyl pyruvatehigh-mobility group box 1Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2587-2599 (2016)
institution DOAJ
collection DOAJ
language EN
topic Pulmonary artery hypertension
ethyl pyruvate
high-mobility group box 1
Medicine (General)
R5-920
spellingShingle Pulmonary artery hypertension
ethyl pyruvate
high-mobility group box 1
Medicine (General)
R5-920
Liu K
Zhang XQ
Cao GQ
Liu YJ
Liu CZ
Sun HR
Pang XY
Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model
description Kai Liu,1 Xiquan Zhang,1 Guangqing Cao,1 Yongjun Liu,2 Chuanzhen Liu,1 Hourong Sun,1 Xinyan Pang1 1Cardiovascular Surgery Department, Qilu Hospital of Shandong University, 2Pharmacy College of Shandong University, Jinan, People’s Republic of China Purpose: To investigate whether inhalation of ethyl pyruvate (EP) encapsulated with poly(ethylene glycol)-block-lactide/glycolide copolymer nanoparticles (EP-NPs) can prevent the development of shunt-flow-induced hyperkinetic pulmonary arterial hypertension (PAH) in a rat model.Materials and methods: Rats were separated into five groups: blank (ie, no treatment after shunt flow), normal control (ie, no shunt flow or treatment), EP-NP instillation, EP-only instillation, and vehicle. The animals received intratracheal instillation of EP-NPs or other treatments immediately after a shunt flow, and treatment continued weekly until the end of the experiment. Hemodynamic data were recorded, pulmonary arterial remodeling was assessed, and levels of inflammatory mediators and ET1 expression in the lung and serum were analyzed. In addition, retention of EP in the lungs of rats in the EP-NP and EP-only groups was measured using high-performance liquid chromatography.Results: After 12 weeks, hemodynamic abnormalities and pulmonary arterial remodeling were improved in the EP-NP instillation group, compared with the blank, EP-only, and vehicle groups (P<0.05). In addition, the EP-NP group showed significantly decreased levels of HMGB1, IL-6, TNFα, reactive oxygen species, and ET1 in the lung during PAH development (P<0.05). Furthermore, EP-NP instillation was associated with reduced serum levels of inflammatory factors and ET1. High-performance liquid-chromatography measurement indicated that EP retention was greater in the lungs of the EP-NP group than in the EP-only group.Conclusion: EP-NP instillation attenuated inflammation and prevented pulmonary arterial remodeling during the development of PAH induced by shunt flow. In the future, EP-NP delivery into the lung might provide a novel approach for preventing PAH. Keywords: pulmonary artery hypertension, ethyl pyruvate, high-mobility group box 1
format article
author Liu K
Zhang XQ
Cao GQ
Liu YJ
Liu CZ
Sun HR
Pang XY
author_facet Liu K
Zhang XQ
Cao GQ
Liu YJ
Liu CZ
Sun HR
Pang XY
author_sort Liu K
title Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model
title_short Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model
title_full Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model
title_fullStr Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model
title_full_unstemmed Intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model
title_sort intratracheal instillation of ethyl pyruvate nanoparticles prevents the development of shunt-flow-induced pulmonary arterial hypertension in a rat model
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/7c9c8fa7f6e649ed8fc5bdee67bb431f
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