Ethyl Pyruvate Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats

Liu, Chuanzhen; Fang, Changcun; Cao, Guangqing; Li, Kai; Wang, Biao; Wan, Zhaojie; Li, Sijie; Wu, Shanshan

doi:10.1097/fjc.0000000000000083

Cited by 13 publications

(11 citation statements)

References 55 publications

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“…We also focused on the inflammatory cytokine MCP-1 because of its important role in patients with idiopathic PAH and MCT-induced PAH [ 43 ]. The expression of MCP-1 increases in several types of PAHs, and the level of MCP-1 in circulation is correlated with disease severity [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

et al. 2018

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Background: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. Several studies have demonstrated that betaine possesses outstanding anti-inflammatory effects. However, whether betaine exerts protective effects on PAH by inhibiting inflammatory responses in the lungs needs to be explored. To test our hypothesis, we aimed to investigate the effects of betaine on monocrotaline-induced PAH in rats and attempted to further clarify the possible mechanisms. Methods: PAH was induced by monocrotaline (50 mg/kg) and oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricle hypertrophy index were used to evaluate the development of PAH. Hematoxylin and eosin staining and Masson staining were performed to measure the extents of vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by immunohistochemical staining. Nuclear factor-κB (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were assessed by Western blot. Results: This study showed that betaine improved the abnormalities in right ventricular systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy index, and pulmonary arterial remodeling induced by monocrotaline compared with the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot indicated that the protein expression levels of NF-κB, TNF-α, and IL-1β significantly decreased (p < 0.01). Conclusion: Our study demonstrated that betaine attenuated PAH through its anti-inflammatory effects. Hence, the present data may offer novel targets and promising pharmacological perspectives for treating monocrotaline-induced PAH.

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Section: Discussionmentioning

confidence: 99%

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

et al. 2018

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“…Previous studies have reported that IL-1β, IL-6 and TNF-α damage pulmonary artery endothelial cells, cause abnormal pulmonary artery smooth muscle cell proliferation and prevent apoptosis, leading to pulmonary arterial remodeling and the promotion of PAH development (3,7). Previous studies have demonstrated that the expression levels of TNF-α, IL-1β and IL-6 are significantly increased in MCT-induced PAH (26,27), and IL-1β and IL-6 promoted pulmonary artery smooth muscle cell proliferation and/or induced vascular intima migration (7). Furthermore, the mRNA and protein expression levels of COX-2 were significantly upregulated in the combination of left pneumonectomy with MCT-treated PAH (28).…”

Section: Discussionmentioning

confidence: 99%

Osthole attenuates pulmonary arterial hypertension in monocrotaline-treated rats

Wang

et al. 2017

Molecular Medicine Reports

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Pulmonary arterial hypertension (PAH) is an insidious and progressive disease that is triggered by various cardiopulmonary diseases. Inflammation has an important role in the progression of PAH. Osthole (Ost) is a coumarin that has clear anti‑inflammatory properties. The present study aimed to investigate the effects of Ost on PAH, and to explore the mechanism underlying this effect. Using the monocrotaline (MCT)‑induced PAH rat model, the effects of Ost on PAH were investigated. Rats were subcutaneously administered a single dose of MCT (50 mg/kg) to establish the PAH model, followed by daily treatment with Ost (10 or 20 mg/kg) by gavage for 28 days. The mean pulmonary arterial pressure (mPAP) was measured and histological analysis was performed. The results demonstrated that Ost significantly decreased mPAP, and reduced thickening of the pulmonary artery, compared with in rats in the MCT group. To further determine whether the effects of Ost on MCT‑induced PAH were associated with inflammatory responses, the nuclear factor‑κB (NF‑κB) p65 signaling pathway was investigated by western blot analysis. The results demonstrated that Ost increased inhibition of the NF‑κB p65 signaling pathway. In conclusion, the results of the present study demonstrate that Ost may suppress the progression of MCT‑induced PAH in rats, which may be, at least partially, mediated through modulation of the NF‑κB p65 signaling pathway.

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“…Our results are consistent with those of others, which reported that EP could decrease pulmonary vasoconstriction and downregulate pulmonary artery proinflammatory cytokine gene expression. 16,31 Our previous study described the effects of EP through intraperitoneal injection on monocrotaline-induced PAH. 16 In the current study, however, EP-only intratracheal instillation did not show any therapeutic effects on PAH.…”

Section: Discussionmentioning

confidence: 99%

“…16,31 Our previous study described the effects of EP through intraperitoneal injection on monocrotaline-induced PAH. 16 In the current study, however, EP-only intratracheal instillation did not show any therapeutic effects on PAH. This might have been due to the different route of administration, and more importantly because the intraperitoneal injection dose was much higher than that used with intratracheal instillation.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, our previous study showed that intraperitoneal injection of EP could attenuate monocrotaline-induced PAH and reverse pulmonary vascular remodeling in rats by inhibiting the release of TNFα and IL-6 and reducing the expression of ET1. 16 Nebulized inhalation appears to be more efficient than systemic drug delivery of targeted therapy in pulmonary disease. Compared with systemic administration, local delivery of a drug would be expected to increase its distribution in the lungs, improve the efficiency of the targeted therapy, eliminate side effects, and avoid first-pass elimination by the liver.…”

Section: Introductionmentioning

confidence: 99%

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

Li¹,

Zhang²,

Cao³

et al. 2016

IJN

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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 highperformance 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.

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Ethyl Pyruvate Ameliorates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats

Abstract: EP ameliorates monocrotaline-induced PAH and reverses pulmonary vascular remolding in rats by inhibiting the release of TNF-α and IL-6 and reducing the expression of ET-1.

Cited by 13 publications

References 55 publications

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

Osthole attenuates pulmonary arterial hypertension in monocrotaline-treated rats

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

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