Blood outgrowth endothelial cells overexpressing eNOS mitigate pulmonary hypertension in rats: a unique carrier cell enabling autologous cell-based gene therapy

Somani, Arif; Nair, Sethu L; Milbauer, Liming; Zhu, Guangshuo; Suchitra, S.; Solovey, Anna; Chen, Yingjie; Hebbel, Robert P.

doi:10.1016/j.trsl.2019.04.005

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…There are many factors causing pulmonary hypertension, including hypoxia, oxidative stress, and the pathological changes in pulmonary vascular structure [ 20 – 22 ]. As a key substance, NO is synthesized by eNOS and can improve the symptom of PAH in patients via alleviating the pressure of arterial artery [ 23 ]. In the PAH rats, the decreased NO level in lung tissues of the PAH rats was observed, and the expression level of eNOS was also found to be downregulated in rPAECs, significantly.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] miR‐1226‐3p Promotes eNOS Expression of Pulmonary Arterial Endothelial Cells to Mitigate Hypertension in Rats via Targeting Profilin‐1

Jian

Liang

2021

BioMed Research International

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In pulmonary arterial hypertension (PAH), microRNAs (miRNAs) are related with dysfunction of pulmonary arterial endothelial cells. miR-1226-3p was found to be downregulated in the serum of PAH patients, while few studies have illustrated the regulation mechanism of miR-1226-3p on PAH. In this study, we aimed to systematically investigate the role of miR-1226-3p in PAH. Sprague-Dawley (SD) rats were treated with monocrotaline (MCT) to establish the PAH models. The right ventricular systolic pressure (RVSP), ratio of the right ventricle to the left ventricle with septum (RV/(LV+S) ratio), and nitric oxide (NO) content were used to reflect the symptom of the rats. The rat models were used to observe the regulation mechanism of miR-1226-3p on PAH, and dual-luciferase reporter assay was used to verify the binding effect of miR-1226-3p to Pfn1. Besides, the qRT-PCR and western blot were used to measure the expression levels of miR-1226-3p and some keys proteins such as eNOS and Pfn1, respectively. The results showed that the PAH models were established successfully. The RVSP levels and the RV/(LV+S) ratio of the PAH rats were higher than those indexes in normal rats, while the NO content showed the opposite trends. Besides, the decreased miR-1226-3p and eNOS were, respectively, found in the PAH rats and rPAECs, and overexpressed miR-1226-3p could reverse the disadvantages of the PAH rats including increased RVSP, high RV/(LV+S) ratio, and decreased NO content. Furthermore, miR-1226-3p could directly target the 3 ′ -UTR of Profilin-1 (Pfn1). Overexpressed Pfn1 led to decreased eNOS, while miR-1226-3p could partly inhibit the expression of Pfn1 and increase the expression level of eNOS in rPAECs. In summary, this study suggests miR-1226-3p as a protector to increase eNOS, improve NO content in rPAECs of the PAH rats via targeting Pfn, and finally protect the rats from the injury induced by PAH.

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Section: Discussionmentioning

confidence: 99%

[Retracted] miR‐1226‐3p Promotes eNOS Expression of Pulmonary Arterial Endothelial Cells to Mitigate Hypertension in Rats via Targeting Profilin‐1

Jian

Liang

2021

BioMed Research International

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“…In addition, decreased NO production contributes to the pathogenesis of PAH in different cell lines and animal models, such as the monocrotaline-induced PAH model. eNOS is underexpressed, and therapeutic treatments increase its expression and NO production, protecting against the injury induced by PAH [76][77][78].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Molecular Mechanism of Chlorogenic Acid in the Treatment of Pulmonary Arterial Hypertension Based on Analysis Network Pharmacology and Molecular Docking

Santos-Álvarez,

Velázquez-Enríquez,

Baltiérrez-Hoyos

2024

JVD

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Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by increased pressure in the pulmonary arteries, which can lead to heart failure and death. Chlorogenic acid (CGA) is a natural compound present in several foods and medicinal plants and has been described to exert a therapeutic effect in various diseases. However, its potential therapeutic effect on PAH remains undeciphered. In this study, the potential of CGA for the treatment of PAH was investigated using network pharmacology analysis and molecular docking. Methods: Potential CGA targets were obtained from the SwissTargetPrediction and GeneCards databases. Moreover, potential PAH targets were collected from the GeneCards and DisGNET databases. Then, common targets were selected, and a protein-protein network (PPI) was constructed between common CGA and PAH targets using the STRING database. The common hub targets were selected, and GO enrichment analysis was performed via KEGG using the DAVID 6.8 database. Additionally, molecular docking analysis was performed to investigate the interaction between CGA and these potential therapeutic targets. Results: We obtained 168 potential targets for CGA and 5779 potential targets associated with PAH. Among them, 133 were common to both CGA and PAH. The main hub targets identified through PPI network analysis were TP53, HIF1A, CASP3, IL1B, JUN, MMP9, CCL2, VEGFA, SRC, IKBKB, MMP2, CASP8, NOS3, MMP1, and CASP1. KEGG pathway analysis showed that these hub targets are associated with pathways such as lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the IL-17 signaling pathway. In addition, the molecular docking results showed a high binding affinity between CGA and the 15 hub PAH-associated targets, further supporting its therapeutic potential. Conclusions: This study provides preliminary evidence on the underlying molecular mechanism of CGA in the treatment of PAH. The findings suggest that CGA could be a promising option for the development of new PAH drugs.

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“…A large number of studies have demonstrated that PIM1 is overactivated in patients with PH, preclinical animal models, or cell models [25][26][27] , and inhibition of PIM1 expression by drug intervention could also effectively delay the progression of PH 26,28 . NOS3, also known as eNOS, is mainly expressed in endothelial cells and could play a protective role in PH vascular remodeling by regulating nitric oxide synthesis [29][30][31] . The above studies show that SRC and PIM1 may participate in the development of PH by promoting the proliferation of PASMCs.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Therapeutic Role of Selected Active Compounds in Plumula Nelumbinis on Pulmonary Hypertension via Network Pharmacology and Experimental Analysis

Xiao

Luo

et al. 2022

Preprint

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Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the most critical factors leading to vascular remodeling in pulmonary hypertension (PH). This study aimed to explore the effect and potential mechanism of Plumula Nelumbinis on PH by using network pharmacology and experimental analysis. The potential active components of Plumula Nelumbinis and their targets were obtained from TCMSP and PharmMapper databases. The PH-related targets were obtained from GeneCards, OMIM, DisGeNET, and TTD databases. Co-targets between Plumula Nelumbinis and PH were obtained by drawing Venn diagrams. The protein-protein interaction networks and compound-target-pathway networks were established using the STRING database and Cytoscape software. Moreover, the binding activities of core targets and essential active compounds were further validated by molecular docking. Finally, we further confirmed in vitro experiments that the main active components of Plumula Nelumbinis could inhibit the proliferation of PASMCs induced by hypoxia, as well as the increased expression of p-SRC and PIM1. Based on these observations, we conclude that multi-components (neferine, liensinine, and isoliensinine) in Plumula Nelumbinis can inhibit the hypoxia-induced proliferation of PASMCs by regulating the expression of p-SRC and PIM1, thereby delaying the development of PH.

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Blood outgrowth endothelial cells overexpressing eNOS mitigate pulmonary hypertension in rats: a unique carrier cell enabling autologous cell-based gene therapy

Cited by 8 publications

References 30 publications

[Retracted] miR‐1226‐3p Promotes eNOS Expression of Pulmonary Arterial Endothelial Cells to Mitigate Hypertension in Rats via Targeting Profilin‐1

[Retracted] miR‐1226‐3p Promotes eNOS Expression of Pulmonary Arterial Endothelial Cells to Mitigate Hypertension in Rats via Targeting Profilin‐1

Evaluation of the Molecular Mechanism of Chlorogenic Acid in the Treatment of Pulmonary Arterial Hypertension Based on Analysis Network Pharmacology and Molecular Docking

Evaluating the Therapeutic Role of Selected Active Compounds in Plumula Nelumbinis on Pulmonary Hypertension via Network Pharmacology and Experimental Analysis

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