Key Regulatory Effect of Activated <i>HIF-1α/VEGFA</i> Signaling Pathway in Systemic Capillary Leak Syndrome Confirmed by Bioinformatics Analysis

Mo, Lujiao; Xu, Guanhua; Wu, Channi; Pan, Kanda; Pan, Ping-Ying; Yu, Lixin; Shen, Xiaoyuan

doi:10.1089/cmb.2019.0222

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…It has been widely reported that VEGF levels are elevated in many SCLS patients, coinciding with the course of the disease ( Lesterhuis et al, 2009 ; Kinoshita et al, 2010 ; Xie et al, 2014 ). Bevacizumab has been suggested as a potential treatment for SCLS patients ( Kouadri et al, 2021 ), and VEGF may be responsible for the immune systems disorder ( Xie et al, 2012 ; Mo et al, 2020 ). VEGF/VEGFR-2 is an important angiogenic signaling pathway that also plays a potential role in lymphangiogenesis ( Liu and Yu, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Chronic systemic capillary leak syndrome with lymphatic capillaries involvement and MYOF mutation: case report and literature review

Gao,

Zhong,

Zhang

et al. 2023

Front. Genet.

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Introduction: Idiopathic systemic capillary leak syndrome (SCLS) is a rare disorder characterized by hemoconcentration, hypoproteinemia and edema. Chronic SCLS (cSCLS) presents as intractable edema, distinguishing it from the classic acute form, and only about 10 cases were reported worldwide. Nevertheless, the underlying pathogenesis of both types is obscure.Case presentation: We report a case of a 58-year-old man with chronic edema persisting for 8 years, complicated by unique chylous polyserous effusions and hypotrichosis, which was successfully relieved by treatment with dexamethasone, intravenous immunoglobulin, and thalidomide. Furthermore, a variant c.5594A>G (p.K1865R) in the MYOF gene was identified as a potentially pathogenic mutation through whole-exome genetic sequencing. The proposed mechanism involves its impact on VEGF signaling, leading to increased capillary permeability.Conclusion: Our case illustrates possible lymphatic capillaries involvement in SCLS, which may plays a potential role in immune disorder, and revealed a possible causative genetic mutation of SCLS.

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Section: Discussionmentioning

confidence: 99%

Chronic systemic capillary leak syndrome with lymphatic capillaries involvement and MYOF mutation: case report and literature review

Gao,

Zhong,

Zhang

et al. 2023

Front. Genet.

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“…The vascular endothelium is implicated in the regulation of vascular tone and structure, and abnormal vascular endothelial function may be a major contributor to the adverse outcomes for patients with hypertension [4,46]. VEGFA is a homologue of the VEGF family, which regulates cell migration, division, and angiogenesis in normal microvascular endothelial cells [47]. Several studies have shown that eNOS significantly contributes to the maintenance of vascular function and cardiovascular homeostasis [48].…”

Section: Discussionmentioning

confidence: 99%

Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

et al. 2021

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Background Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. Methods The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. Results A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C–C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats. Conclusion The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

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“…[4,40] VEGFA serves as a homologue of the VEGF family and regulates cell migration, division, and angiogenesis regulation in normal microvascular endothelial cells. [41] Several studies have provided evidence that eNOS is a signi cant contributor in the maintenance of vascular function and cardiovascular homeostasis. [42] NO, produced by eNOS, mediates control of the in ammatory process as well as regulation of neoangiogenesis and vasodilatation.…”

Section: Discussionmentioning

confidence: 99%

Potential Mechanism of Guizhi Decoction in Hypertension Treatment Based on Network Pharmacology and Dahl Salt-Sensitive Rat Model

Chen

Zhang

Wang

et al. 2020

Preprint

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Introduction: Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore its therapeutic effects and potential mechanisms in the treatment of hypertension using network pharmacology and experimental validation.Methods: The active ingredients and corresponding targets were collected from Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from multiple databases, and multiple networks were constructed to identify key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD on hypertension. Results: A total of 112 active ingredients, 222 targets of GZD and 341 hypertension- related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets to perform experimental verification, including interleukin 6 (IL-6), C-C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2(MMP-2), and MMP9. Pathway enrichment results indicated that 56 overlapping targets mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD showed tight binding ability with the key targets. Experimental results demonstrated that compared with the group fed a high-salt diet in this study, the GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL6, CCL2, IL1β, MMP2 and MMP9 in rats.Conclusions: The potential mechanism of the therapeutic effect of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

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Key Regulatory Effect of Activated HIF-1α/VEGFA Signaling Pathway in Systemic Capillary Leak Syndrome Confirmed by Bioinformatics Analysis

Cited by 6 publications

References 26 publications

Chronic systemic capillary leak syndrome with lymphatic capillaries involvement and MYOF mutation: case report and literature review

Chronic systemic capillary leak syndrome with lymphatic capillaries involvement and MYOF mutation: case report and literature review

Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

Potential Mechanism of Guizhi Decoction in Hypertension Treatment Based on Network Pharmacology and Dahl Salt-Sensitive Rat Model

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