Hereditary angioedema: Linking complement regulation to the coagulation system

Levi, Marcel; Cohn, Danny M.

doi:10.1002/rth2.12175

Cited by 33 publications

(20 citation statements)

References 60 publications

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“…Abnormal metabolites, including prostaglandins, leukotrienes, lipid peroxidation and inflammatory mediation, may contribute to vasoconstriction and inflammatory syndrome, eventually resulting in adverse perinatal outcomes [53][54][55]. Complement and coagulation cascades contribute to homeostasis, thrombosis, defense infection, immune tolerance and apoptotic cell clearance [56,57]. Abnormalities in these cascades may lead to recurrent pregnancy loss, vascular complications and preeclampsia [58,59].…”

Section: Discussionmentioning

confidence: 99%

The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer

Zhao¹,

Zheng²,

Liu³

et al. 2019

Reprod Biol Endocrinol

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Background: The placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET). Methods: This study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools. Results: A total of 3405 differentially regulated genes were identified as significantly dysregulated (> 2-fold change; P < 0.05) in the IVF-ET placenta in the first trimester: 1910 upregulated and 1495 downregulated genes. Functional enrichment analysis of the differentially regulated genes demonstrated that the genes were involved in more than 50 biological processes and pathways that have been shown to play important roles in the first trimester in vivo. These pathways can be clustered into coagulation cascades, immune response, transmembrane signaling, metabolism, cell cycle, stress control, invasion and vascularization. Nearly the same number of up-and downregulated genes participate in the same biological processes related to placental development and maintenance. Procedures utilized in IVF-ET altered the expression of first-trimester placental genes that are critical to these biological processes and triggered a compensatory mechanism during early implantation in vivo. Conclusion: These data provide a potential basis for further analysis of the higher frequency of adverse perinatal outcomes following IVF-ET, with the ultimate goal of developing safer IVF-ET protocols.

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Section: Discussionmentioning

confidence: 99%

The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer

Zhao¹,

Zheng²,

Liu³

et al. 2019

Reprod Biol Endocrinol

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“…Its increasing concentration was found to be associated with resistance to cell lysis, hence enhancing and promoting tumor growth and expansion [31,32]. However, the expression of CD antigens is equivocally interpreted: for example, the expression of CD55 is associated with colorectal carcinoma [33], but the loss of CD55 is associated with breast cancer [34,35].…”

Section: Implication Of Complement Systems In Crc Development and Surmentioning

confidence: 99%

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

et al. 2020

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Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I–II and III–IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I–II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.

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“…C1-INH plays an important role in the regulation of not only the classical pathway of the immune system but also the plasminogen-plasmin and kallikrein-kinin systems (contact system), and coagulation/fibrinolysis [ 8 ]. The deficiency or dysfunction of C1-INH in patients with HAE predominantly results in the increased activation of bradykinin by kallikrein, which leads to vasodilation, an increase in vascular permeability, and the typical angioedema of HAE.…”

Section: Discussionmentioning

confidence: 99%

Capillary leak syndrome and disseminated intravascular coagulation after kidney transplantation in a patient with hereditary angioedema - A case report -

et al. 2021

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Background: Hereditary angioedema (HAE) is a rare disease caused by the deficiency of C1 esterase inhibitor. HAE has a risk of life-threatening complications such as capillary leak syndrome (CLS) and disseminated intravascular coagulation (DIC).Case: A 42-year-old man with HAE presented for deceased-donor kidney transplantation. Prophylactic fresh frozen plasma (FFP) was given before surgery because of the risk of edema development. With careful management during anesthesia, there were no problems during surgery. However, generalized edema, hypotension, hypoalbuminemia, massive drainage of serosanguineous fluids from the intraabdominal space, and DIC occurred on the day after surgery. CLS was suspected and sustained hypotension with generalized edema became worse despite treatment with albumin, danazol, FFP, and vasoactive drugs. The patient’s condition worsened despite intensive care and he died due to shock.Conclusions: The anesthesiologist should prepare for the critical complications of HAE and prepare the appropriate treatment options.

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Hereditary angioedema: Linking complement regulation to the coagulation system

Cited by 33 publications

References 60 publications

The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer

The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

Capillary leak syndrome and disseminated intravascular coagulation after kidney transplantation in a patient with hereditary angioedema - A case report -

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