Betaine alleviates right ventricular failure via regulation of Rho A/ROCK signaling pathway in rats with pulmonary arterial hypertension

Lv, Yingjie; Ma, Peng-Sheng; Wang, Jialing; Chen, Nansheng; Fan, Jianling; Yang, Lin; Ma, Ping; Zhou, Ran

doi:10.1016/j.ejphar.2021.174311

Cited by 9 publications

(7 citation statements)

References 42 publications

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“…Several studies have shown that the role of NF‐kB in PAH is important: pulmonary artery smooth muscle cells and macrophages from patients with idiopathic PAH show increased NF‐kB activation, and NF‐kB inhibition ameliorates MCT‐induced PAH 26 . Further to this, our study found that betaine treatment reduced mPAP and RVSP in MCT‐induced PAH rats and alleviated pulmonary artery and right ventricular remodelling, and reduced MCT‐induced expression of monocyte chemoattractant protein‐1 and endothelin‐1 by down‐regulating the NF‐κB signalling pathway, thus inhibiting the inflammatory response 16 . PAH is a rare but severe disease that can progress to severe haemodynamic disorders and death during the terminal phase 27 .…”

Section: Discussionsupporting

confidence: 75%

“…26 Further to this, our study found that betaine treatment reduced mPAP and RVSP in MCT-induced PAH rats and alleviated pulmonary artery and right ventricular remodelling, and reduced MCT-induced expression of monocyte chemoattractant protein-1 and endothelin-1 by down-regulating the NF-κB signalling pathway, thus inhibiting the inflammatory response. 16 PAH is a rare but severe disease that can progress to severe haemodynamic disorders and death during the terminal phase. 27 The RVF directly influences the functional status of PAH and is closely associated with prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Our previous study preliminarily found that betaine treatment reduced mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) induced by monocrotaline (MCT) in PAH model rats, attenuated pulmonary artery and right ventricular remodelling, and attenuated pulmonary fibrosis by attenuating vascular remodelling through modulation of the NF-κB signalling pathway, which suppressed inflammatory responses. 16 Further research found that betaine treatment improved haemodynamics, histomorphological parameters and echocardiographic changes in PAH rats. It can alleviate pulmonary vascular remodelling and excessive apoptosis of cardiomyocytes induced by MCT and protect against PAH-induced RVF, which is related to the inhibition of the activation of the Rho A/ROCK signalling pathway.…”

Section: Introductionmentioning

confidence: 96%

“…Inflammation plays an important role in the occurrence and development of pulmonary hypertension, and NF‐kB is a central regulator of target genes associated with inflammation, endothelial cell dysfunction and angiogenesis 14,15 . Our previous study preliminarily found that betaine treatment reduced mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) induced by monocrotaline (MCT) in PAH model rats, attenuated pulmonary artery and right ventricular remodelling, and attenuated pulmonary fibrosis by attenuating vascular remodelling through modulation of the NF‐κB signalling pathway, which suppressed inflammatory responses 16 . Further research found that betaine treatment improved haemodynamics, histomorphological parameters and echocardiographic changes in PAH rats.…”

Section: Introductionmentioning

confidence: 99%

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Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension

Che,

Xia,

Liu

et al. 2023

Basic Clin Pharma Tox

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Pulmonary arterial hypertension (PAH) is a life‐threatening disease characterised by elevated pulmonary pressure, right ventricular failure (RVF) and ultimately death. Aggressive treatment of RVF is considered an important therapeutic strategy to treat PAH. Previous studies have indicated that betaine may be may a promising therapeutic approach for PAH‐induced RVF. Therefore, in this study, betaine solution for injection was prepared and characterised using various techniques. The therapeutic efficacy of three different methods of administration (intragastric, nebulised inhalation and intravenous injection) were comprehensively evaluated in terms of pharmacokinetics, tissue distribution and pharmacodynamics. The pharmacokinetic results demonstrated that betaine injection administered via nebulised inhalation significantly prolonged betaine's half‐life and increased its internal circulation time compared to the intragastric and intravenous routes. Biodistribution experiments verified that the betaine formulation accumulated in the lung tissue when administered via inhalation. The results of the pharmacodynamic analysis further confirmed that right ventricular systolic pressure, mean pulmonary artery pressure and right ventricular hypertrophy index increased in the model group and that inhaled betaine suppressed these pathological changes to a level comparable to those observed in the control group. Taken together, these results indicate that betaine administered by inhalation is a promising strategy for the treatment of PAH‐induced RVF.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension

Che,

Xia,

Liu

et al. 2023

Basic Clin Pharma Tox

Self Cite

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“…Another recent study demonstrated that miR-638 induced apoptosis through regulating STARD10 signaling, the expression of miR-638 was inversely correlated with the expression of STARD10 mRNA ( Zhao et al, 2017 ). Several previous studies have shown that apoptosis play a vital role in pulmonary arterial hypertension ( Lv et al, 2021 ; Zimmer et al, 2021 ), indicating that the association of miR-638 with PAH may be partially related to STARD10, a target gene of miR-638.…”

Section: Discussionmentioning

confidence: 99%

Effect of Xuezhikang Therapy on Expression of Pulmonary Hypertension Related miR-638 in Patients With Low HDL-C Levels

Cao¹,

Sun²,

Xu³

et al. 2021

Front. Pharmacol.

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Objective: Low plasma level of high-density lipoprotein cholesterol (HDL-C) associated with poor outcomes in several cardiovascular diseases, including pulmonary arterial hypertension (PAH). Regulation of miR-638 have been proved to be associated with PAH. The aim of this study was to evaluate the expression of miR-638 after Xuezhikang (XZK) therapy in patients with low HDL-C.Methods: Plasma levels of miR-638 were quantified by real-time polymerase chain reactions in 20 patients with PAH and 30 healthy controls. A total of 40 subjects with low HDL-C were assigned to receive an XZK therapy for 6 months. The miR-638 expression profiles were detected in PAH patients, XZK-treated subjects and lovastatin treated pulmonary arterial smooth muscle cells (PA-SMCs).Results: The relative expression level of miR-638 in the plasma was lower in the PAH patients than that in the controls (p < 0.001). An increase of 11.2% from baseline in the HDL-C level was found after XZK therapy (p < 0.001). The relative expression of miR-638 was increased after XZK treatment (p < 0.01). The changes of miR-638 were inversely associated with baseline HDL-C levels. A significantly reduction in miR-638 expression were found in PDGF-BB-treated hPA-SMCs compared to the control cells, and the pre-treatment of the cells with lovastatin significantly re-gain the expression levels in miR-638.Conclusion: In patients with low HDL-C levels, XZK therapy raised the expression of miR-638, suggesting that the potential therapeutic effect of XZK in PAH patients with low serum HDL-C levels deserves further exploration.

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Advances in the potential of nebulized inhalation for the treatment of pulmonary arterial hypertension

Lu,

Baima,

et al. 2024

Current Problems in Cardiology

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Betaine alleviates right ventricular failure via regulation of Rho A/ROCK signaling pathway in rats with pulmonary arterial hypertension

Cited by 9 publications

References 42 publications

Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension

Preparation of betaine injection and its therapeutic effect in pulmonary arterial hypertension

Effect of Xuezhikang Therapy on Expression of Pulmonary Hypertension Related miR-638 in Patients With Low HDL-C Levels

Advances in the potential of nebulized inhalation for the treatment of pulmonary arterial hypertension

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