Prophylactic supplementation of 20-HETE ameliorates hypoxia/reoxygenation injury in pulmonary vascular endothelial cells by inhibiting apoptosis

Sugumaran, Praveenkumar; Narayanan, Vishnusekar; Zhu, Daling; Medhora, Meetha; Jacobs, Elizabeth R.; Chandramohan, Yamini; Vimalraj, Selvaraj; Dhanasekaran, Anuradha

doi:10.1016/j.acthis.2019.151461

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…Among the top 30 pathways of pathogenetic genes (Figure 2E), more than 10 pathways are related to stroke. For example, the pathway Cytokine-cytokine receptor interaction is related to cerebral ischemia-reperfusion injury (Wang et al, 2017) and is one of the important active pathways after stroke ; the HIF-1 signaling pathway is related to the neuromodulation (Xu H. et al, 2019;Yang W. et al, 2020), cellular activity (Sugumaran et al, 2020), ischemic angiogenesis , and inflammation (Liu R. et al, 2019;Du et al, 2020). Furthermore, ischemic stroke has 14 similar pathogenetic genes, ACVRL1, APP, ABCC6, CST3, ENG, F7, JAK2, PLAT, PLAU, VHL, SH2B3, PDCD10, KIF1B, and CCM2, and has 48 similar signaling pathways to hemorrhagic stroke, whereas the stroke-related ID C0553692 is related to hemorrhagic stroke and to 29 pathogenetic genes and 48 signaling pathways.…”

Section: Identification Of Pathogenetic Genesmentioning

confidence: 99%

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

Chen

Wang

Cai

et al. 2022

Front. Cell Dev. Biol.

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Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM.

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Section: Identification Of Pathogenetic Genesmentioning

confidence: 99%

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

Chen

Wang

Cai

et al. 2022

Front. Cell Dev. Biol.

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“…In addition to CYP4Fs catalyzing the formation of 20-HETE, these enzymes also ω-hydroxylate and deactivate proinflammatory 5-, 8-, and 12-HETE, suggesting the dual roles for the P450 ω-hydroxylases in both the initiation and resolution phases of inflammation [ 22 ]. 20-HETE protects pulmonary vascular endothelial cells (PMVEC) under normoxia and hypoxia [ 23 ]. CYP4Fs/20-HETE has been reported to enhance angiogenesis, pulmonary vascular tone, and endothelial nitric oxide synthase function [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Suggestive evidence of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population

Wang

et al. 2023

PLoS ONE

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High altitude pulmonary edema (HAPE) is a common respiratory disease in the high altitude area, which is rapid and harmful. We firstly conducted a case-control study to assess the potential association of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population. The study recruited 238 patients with HAPE and 230 healthy controls in Northwest China. Genomic DNA was extracted from blood samples, and gene polymorphisms were detected using the Agena MassARRAY platform. Odds ratios (ORs), 95% confidence intervals (95% CIs), and P-value were used to evaluate the relationship between HAPE risk and CYP4F2 gene polymorphisms. Multi-factor dimension reduction (MDR) was used to assess the optimal interaction of CYP4F2 gene polymorphisms on HAPE risk. We found rs3093193 was shown to reduce the risk of HAPE (OR = 0.70, 95% CI = 0.52–0.93, P = 0.014), while rs12459936 was increased the susceptibility to HAPE (OR = 2.08, 95% CI = 1.33–3.26, P = 0.001). Age stratified analysis revealed that rs3093193 and rs12459936 were correlated with HAPE risk in people at age > 32 years old, and rs3093193 and rs3093110 were correlated with the HAPE risk in people at age ≤ 32 years old. Gender stratification analysis was found that rs3093193, rs12459936, and rs3093110 were all related to HAPE risk in males. A combination of rs12459936 and rs3093110 was the best multi-loci model with the highest testing accuracy. Our study is the first to provide the association between CYP4F2 gene polymorphisms and HAPE risk in the Chinese Han population.

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“…Moreover, as a complex inflammatory response, I/R injury entails endothelial and epithelial injury/dysfunction [ 3 ]. It has been reported that when endothelial cells are exposed to hypoxia and reoxygenation (H/R) stimulation, endothelial cell-vascular interactions are disturbed, permeability is altered, proliferation of peripheral smooth muscle cells is disrupted, and apoptosis is induced [ 4 , 5 ]. H/R-induced apoptosis of endothelial cells can lead to pulmonary arterial hypertension, pulmonary edema and fibrosis [ 4 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-141-3p reduces pulmonary hypoxia/reoxygenation injury through suppression of Beclin-1-dependent autophagy

Zhan,

Li,

Guo

et al. 2024

Aging

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Alterations in autophagy are involved in pulmonary hypoxia/reoxygenation (H/R)-induced injury. Here, we intended to explain the function of microRNA-141-3p (miR-141-3p) in regulating autophagy under the H/R condition. Rat pulmonary microvascular endothelial cells (PMVECs) were applied for H/R cell model establishment, followed by tracing of autophagy formation. SIRT1 plays a critical role in controlling the lifespan of yeast, flies, and mice. Interaction between SIRT1 and Beclin-1, an indicator protein for autophagy, and between miR-141-3p and SIRT1 was assayed with their roles in PMVEC injury. Autophagy of PMVECs was activated after hypoxia treatment and further activated after H/R treatment. The binding of miR-141-3p and SIRT1 was verified. In H/R-treated PMVECs, the binding of miR-141-3p and SIRT1 was reduced. Furthermore, SIRT1 acted as a deacetylase to stabilize the Beclin-1 protein, promoting autophagy and PMVEC injury. H/R rat models were established, and in vivo , experiments further confirmed that miR-141-3p regulated autophagy and lung injury in H/R rats through SIRT1/Beclin-1 axis. The current study highlighted that reduced miR-141-3p in H/R-treated PMVECs promoted deacetylation of Beclin-1 by SIRT1, thus causing PMVEC injury.

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Prophylactic supplementation of 20-HETE ameliorates hypoxia/reoxygenation injury in pulmonary vascular endothelial cells by inhibiting apoptosis

Cited by 8 publications

References 28 publications

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

Suggestive evidence of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population

MicroRNA-141-3p reduces pulmonary hypoxia/reoxygenation injury through suppression of Beclin-1-dependent autophagy

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