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

Authors Liu K, Zhang X, Cao G, Liu Y, Liu C, Sun H, Pang X

Received 26 December 2015

Accepted for publication 17 March 2016

Published 3 June 2016 Volume 2016:11 Pages 2587—2599


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Kai Liu,1 Xiquan Zhang,1 Guangqing Cao,1 Yongjun Liu,2 Chuanzhen Liu,1 Hourong Sun,1 Xinyan Pang1

Cardiovascular 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

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