Magnesium lithospermate B prevents phenotypic transformation of pulmonary arteries in rats with hypoxic pulmonary hypertension through suppression of NADPH oxidase

Li, Tao; Luo, Xiu-Ju; Wang, E-Li; Li, Nian-Sheng; Zhang, Xiaojie; Song, Fenglin; Yang, Jinfu; Liu, Bin; Peng, Jun

doi:10.1016/j.ejphar.2019.01.020

Cited by 26 publications

(23 citation statements)

References 22 publications

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“…Aquaporin (AQP), a family of water-selective membrane channels promoting endothelial cell migration and angiogenesis [ 31 ], was found to be overexpressed in PAH patients [ 32 , 33 ], indicating its potential role in the treatment of PAH. Secreted phosphoprotein 1 (SPP1, also known as osteopontin or OPN), a key mediator secreted by SMCs, contributes to the genesis and progression of pulmonary hypertension by enhancing PVSMC proliferation [ 34 – 36 ]. It is upregulated in the lung tissues of patients, and the SPP1 expression level is associated with the severity of PAH [ 37 – 39 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analyses of miRNA-mRNA Network and Potential Drugs in Idiopathic Pulmonary Arterial Hypertension

Zhang

et al. 2020

BioMed Research International

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Introduction. Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiopulmonary disease with a relatively low survival rate. Moreover, the pathogenesis of IPAH has not been fully recognized. Thus, comprehensive analyses of miRNA-mRNA network and potential drugs in IPAH are urgent requirements. Methods. Microarray datasets of mRNA and microRNA (miRNA) in IPAH were searched and downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMIs) were identified. Then, the DEMI-DEG network was conducted with associated comprehensive analyses including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis, while potential drugs targeting hub genes were investigated using L1000 platform. Results. 30 DEGs and 6 DEMIs were identified in the lung tissue of IPAH. GO and KEGG pathway analyses revealed that these DEGs were mostly enriched in antimicrobial humoral response and African trypanosomiasis, respectively. The DEMI-DEG network was conducted subsequently with 4 DEMIs (hsa-miR-34b-5p, hsa-miR-26b-5p, hsa-miR-205-5p, and hsa-miR-199a-3p) and 16 DEGs, among which 5 DEGs (AQP9, SPP1, END1, VCAM1, and SAA1) were included in the top 10 hub genes of the PPI network. Nimodipine was identified with the highest CMap connectivity score in L1000 platform. Conclusion. Our study conducted a miRNA-mRNA network and identified 4 miRNAs as well as 5 mRNAs which may play important roles in the pathogenesis of IPAH. Moreover, we provided a new insight for future therapies by predicting potential drugs targeting hub genes.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analyses of miRNA-mRNA Network and Potential Drugs in Idiopathic Pulmonary Arterial Hypertension

Zhang

et al. 2020

BioMed Research International

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“…This finding is in line with a previous report by Foudi et al who demonstrated that inflammatory cytokines could reduce PGI 2 through modulating protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) pathways, and the imbalances of TXA 2 /PGI 2 were linked with enhanced platelet aggregation, leading to vascular dysfunction in case of hypoxia ( Foudi et al, 2017 ). Pulmonary artery smooth muscle could specifically express contraction protein α-SMA under the normal physiological condition, which played an important role in the regulation of pulmonary artery pressure ( Liu et al, 2017 ; Li et al, 2019 ). Hence, we measured the expression of α-SMA in lung tissues in this model.…”

Section: Discussionmentioning

confidence: 99%

Association Between Inflammatory Mediators and Pulmonary Blood Flow in a Rabbit Model of Acute Pulmonary Embolism Combined With Shock

Wang

Liu

et al. 2020

Front. Physiol.

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Background The pro-inflammatory cytokines were detected in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) tissues to explore the role of inflammation responses and their relationship with the pulmonary blood flow in a rabbit model of acute pulmonary embolism combined with shock. Methods and Results Nineteen rabbits were randomly divided into sham operation group (S group, n = 8) and massive PE (MPE group, n = 11). The MPE model was established by injecting the autologous blood clots into the main pulmonary artery of rabbit. Pulmonary angiography showed that the pulmonary circulation time was significantly prolonged in the MPE group, and pulmonary blood flow was attenuated at 120 min post PE. Hematoxylin–eosin (HE) staining revealed enhanced inflammatory cell infiltration around the pulmonary vessels in PE and non-PE tissues, and obvious edema on the perivascular region. Meanwhile, the expressions of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg-1) in pulmonary vascular and alveolar tissues were significantly upregulated and the iNOS/Arg-1 ratio was significantly higher in the MPE group than in the S group. Moreover, the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were also significantly increased in PE and non-PE tissues, and interleukin-6 (IL-6) level was significantly increased in non-PE tissues in the MPE group as compared to the S group. Thromboxane A2 (TXA 2 ) and alpha smooth muscle actin (α-SMA) levels were significantly higher in both PE and non-PE tissues in the MPE group than in the S group. Conclusion Activation of inflammation mediators in PE and non-PE tissues might be one of the crucial factors responsible for pulmonary vasculature constriction and pulmonary blood flow attenuation in this MPE model.

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“…VAS2870. VAS2870 is a pan-NOX inhibitor that plays a beneficial role in various preclinical disease models, such as stroke (Table 2), Alzheimer's disease [61], and pulmonary hypertension [62]. Kleinschnitz et al used VAS2870 in an experimental model of stroke and found that it has a protective effect in ischemic brain injury, thereby improving neurological function [28,50].…”

Section: New Small-molecule Nadph Oxidase Inhibitors In the Treatmentmentioning

confidence: 99%

Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke‐Induced Oxidative Stress

Duan

Gao

et al. 2021

Oxidative Medicine and Cellular Longevity

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Stroke is a leading cause of death and disability in humans. The excessive production of reactive oxygen species (ROS) is an important contributor to oxidative stress and secondary brain damage after stroke. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme complex consisting of membrane subunits and cytoplasmic subunits, regulates neuronal maturation and cerebrovascular homeostasis. However, NADPH oxidase overproduction contributes to neurotoxicity and cerebrovascular disease. NADPH oxidase has been implicated as the principal source of ROS in the brain, and numerous studies have shown that the knockout of NADPH exerts a protective effect in the model of ischemic stroke. In this review, we summarize the mechanism of activation of the NADPH oxidase family members, the pathophysiological effects of NADPH oxidase isoforms in ischemic stroke, and the studies of NADPH oxidase inhibitors to explore potential clinical applications.

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Magnesium lithospermate B prevents phenotypic transformation of pulmonary arteries in rats with hypoxic pulmonary hypertension through suppression of NADPH oxidase

Cited by 26 publications

References 22 publications

Comprehensive Analyses of miRNA-mRNA Network and Potential Drugs in Idiopathic Pulmonary Arterial Hypertension

Comprehensive Analyses of miRNA-mRNA Network and Potential Drugs in Idiopathic Pulmonary Arterial Hypertension

Association Between Inflammatory Mediators and Pulmonary Blood Flow in a Rabbit Model of Acute Pulmonary Embolism Combined With Shock

Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke‐Induced Oxidative Stress

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