Hypoxia-inducible-factor-1 in trauma and critical care

Bogdanovski, Dorian A.; DiFazio, Louis T.; Bogdanovski, Anastasia K.; Csóka, Balázs; Jordan, Garrett B.; Paul, Elina R.; Antonioli, Luca; Pilip, Stefanie A.; Németh, Zoltán

doi:10.1016/j.jcrc.2017.07.029

Cited by 24 publications

(26 citation statements)

References 51 publications

(75 reference statements)

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“…The clot fibrin matrix thereafter provides a scaffold for migrating peripheral blood cells (PBCs), e.g., neutrophils, macrophages, lymphocytes, and other cell types (e.g., fibroblasts, endothelial cells) [12][13][14]. As a result of vascular trauma and the consequent disruption in oxygen supply, PBCs are exposed to local hypoxia, which leads to the production and release of pro-angiogenic growth factors that stimulate new vessel formation and reestablishment of the wound bed's microcirculation [15][16][17][18]. Thus, the main purpose of the application of blood-derived secretomes in wounded or ischaemic tissues is the targeted stimulation and support of the cellular responses that naturally drive angiogenesis and tissue repair, via protein growth factor signalling.…”

Section: Introductionmentioning

confidence: 99%

Comparative Evaluation of the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes and Platelet-Rich Plasma: An In Vitro Analysis

et al. 2020

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Blood-derived factor preparations are being clinically employed as tools for promoting tissue repair and regeneration. Here we set out to characterize the in vitro angiogenic potential of two types of frequently used autologous blood-derived secretomes: platelet-rich plasma (PRP) and hypoxia preconditioned plasma (HPP)/serum (HPS). The concentration of key pro-angiogenic (VEGF) and anti-angiogenic (TSP-1, PF-4) protein factors in these secretomes was analyzed via ELISA, while their ability to induce microvessel formation and sprouting was examined in endothelial cell and aortic ring cultures, respectively. We found higher concentrations of VEGF in PRP and HPP/HPS compared to normal plasma and serum. This correlated with improved induction of microvessel formation by PRP and HPP/HPS. HPP had a significantly lower TSP-1 and PF-4 concentration than PRP and HPS. PRP and HPP/HPS appeared to induce similar levels of microvessel sprouting; however, the length of these sprouts was greater in HPP/HPS than in PRP cultures. A bell-shaped angiogenic response profile was observed with increasing HPP/HPS dilutions, with peak values significantly exceeding the PRP response. Our findings demonstrate that optimization of peripheral blood cell-derived angiogenic factor signalling through hypoxic preconditioning offers an improved alternative to simple platelet concentration and release of growth factors pre-stored in platelets.

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Section: Introductionmentioning

confidence: 99%

Comparative Evaluation of the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes and Platelet-Rich Plasma: An In Vitro Analysis

et al. 2020

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“…Hypoxia results in an increase of EPO level via activation of HIF-1-EPO pathway, which protects the organs from hypoxic conditions [1]. When HIF-1a was interfered with siRNA, the expression of EPO in EPC decreased after 12 h, while the early detection at 6 h showed no significant difference.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, the centre of fracture or bone defect presents an oxygen-deficient environment. In severe hypoxia, hypoxia-inducible factor (HIF-1) is activated [1], which acts as a transcription factor and regulates the metabolism and function of body to adapt to hypoxic situations [2]. In vivo, hypoxia microenvironment increases the transcriptional activity of HIF-1a mRNA.…”

Section: Introductionmentioning

confidence: 99%

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EPO could be regulated by HIF-1 and promote osteogenesis and accelerate bone repair

Zhang

Sun

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Bone defects caused by many factors prompt further study of pathological process and restoration methods. This study was aimed to clarify the effect of erythropoietin on the repair of bone defect. We added the designated concentration of rhEPO to endothelial progenitor cells and marrow stromal cells, then detected its osteogenic and angiogenesis effects. The results showed that rhEPO promoted the proliferation of EPC and ST2 by promoting the mitosis without affecting cell apoptosis. The protein and mRNA levels of angiogenesis and osteogenic related factors exhibited higher expressions. Additionally, rhEPO encapsulated in PLGA scaffolds accelerated the new bone formation in rat calvaria bone defect model. Since the centre of bone defect was hypoxia environment, we cultured EPC and ST2 under hypoxia. SiRNA and an inhibitor of HIF-1 were used to interfere HIF-1, then the following changes of VEGF and EPO were detected. The results showed that all the factors were upregulated under the hypoxia environment. The expression of VEGF at protein and mRNA level decreased as HIF-1 was inhibited or interfered from 6 h, while the mRNA expression of EPO from 6 h and changed significantly at protein level from 12 h. Therefore, EPO is a promising factor for further studies.

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“…In addition, many studies [94][95][96][97] have confirmed that the RAS system is closely related to proteinuria caused by various diseases, such as diabetic nephropathy and CKD. CKD is associated with hypoxia which can activate HIF-1 [98] and induce profibrogenic changes in proximal tubular epithelial cells and interstitial fibroblasts, leading to further aggravation of proteinuria [99]. Additionally, it has been demonstrated that proteinuria can activate the local RAS system in the kidneys, which can then cause vasoconstriction and subsequent hypoxia [100].…”

Section: Hif-1 Ras Vegf and Age-rage Signaling Pathwaymentioning

confidence: 99%

Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

Hao

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Shuangbai Tablets (SBT), a traditional herbal mixture, has shown substantial clinical efficacy. However, a systematic mechanism of its active ingredients and pharmacological mechanisms of action against proteinuria continues being lacking. A network pharmacology approach was effectual in discovering the relationship of multiple ingredients and targets of the herbal mixture. This study aimed to identify key targets, major active ingredients, and pathways of SBT against proteinuria by network pharmacology approach combined with thin layer chromatography (TLC). Human phenotype (HP) disease analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking were used in this study. To this end, a total of 48 candidate targets of 118 active ingredients of SBT were identified. Network analysis showed PTGS2, ESR1, and NOS2 to be the three key targets, and beta-sitosterol, quercetin, and berberine were the three major active ingredients; among them one of the major active ingredients, quercetin, was discriminated by TLC. These results of the functional enrichment analysis indicated that the most relevant disease including these 48 candidate proteins is proteinuria, SBT treated proteinuria by sympathetically regulating multiple biological pathways, such as the HIF-1, RAS, AGE-RAGE, and VEGF signaling pathways. Additionally, molecular docking validation suggested that major active ingredients of SBT were capable of binding to HIF-1A and VEGFA of the main pathways. Consequently, key targets, major active ingredients, and pathways based on data analysis of SBT against proteinuria were systematically identified confirming its utility and providing a new drug against proteinuria.

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Hypoxia-inducible-factor-1 in trauma and critical care

Cited by 24 publications

References 51 publications

Comparative Evaluation of the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes and Platelet-Rich Plasma: An In Vitro Analysis

Comparative Evaluation of the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes and Platelet-Rich Plasma: An In Vitro Analysis

EPO could be regulated by HIF-1 and promote osteogenesis and accelerate bone repair

Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

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