Interaction of endothelial cells with macrophages—linking molecular and metabolic signaling

Kalucka, Joanna; Bierhansl, Laura; Wielockx, Ben; Carmeliet, Peter; Eelen, Guy

doi:10.1007/s00424-017-1946-6

Cited by 41 publications

(36 citation statements)

References 94 publications

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“…The EMBO Journal Glutamine and asparagine in angiogenesis Hongling Huang et al ex vivo treatment of aortic rings with CB-839 did not affect vasorelaxation ( Fig 2T and U). Second, we assessed the expression of the adhesion molecules VCAM and E-selectin upon IL-1b stimulation in order to explore whether glutamine metabolism affected the activation of the endothelium in conditions of vascular inflammation (Kalucka et al, 2017). GLS1 inhibition did, however, not alter the expression of these markers ( Fig 2V) or the adhesion of leukocytes ( Fig 2W).…”

Section: Aucmentioning

confidence: 99%

Role of glutamine and interlinked asparagine metabolism in vessel formation

et al. 2017

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Endothelial cell (EC) metabolism is emerging as a regulator of angiogenesis, but the precise role of glutamine metabolism in ECs is unknown. Here, we show that depriving ECs of glutamine or inhibiting glutaminase 1 (GLS1) caused vessel sprouting defects due to impaired proliferation and migration, and reduced pathological ocular angiogenesis. Inhibition of glutamine metabolism in ECs did not cause energy distress, but impaired tricarboxylic acid (TCA) cycle anaplerosis, macromolecule production, and redox homeostasis. Only the combination of TCA cycle replenishment plus asparagine supplementation restored the metabolic aberrations and proliferation defect caused by glutamine deprivation. Mechanistically, glutamine provided nitrogen for asparagine synthesis to sustain cellular homeostasis. While ECs can take up asparagine, silencing asparagine synthetase (ASNS, which converts glutamine-derived nitrogen and aspartate to asparagine) impaired EC sprouting even in the presence of glutamine and asparagine. Asparagine further proved crucial in glutamine-deprived ECs to restore protein synthesis, suppress ER stress, and reactivate mTOR signaling. These findings reveal a novel link between endothelial glutamine and asparagine metabolism in vessel sprouting.

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Section: Aucmentioning

confidence: 99%

Role of glutamine and interlinked asparagine metabolism in vessel formation

et al. 2017

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“…In this early inflammatory phase, monocytes are polarized into pro-inflammatory subtypes that secrete inflammatory chemokines and are responsible for the phagocytosis of apoptotic cells and debris. After the acute inflammatory phase, a subpopulation of reparative macrophages initiates the healing process by secreting pro-angiogenic growth factors such as vascular endothelial growth factor-α (VEGFα), platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β) and insulin-like growth factor-1 (IGF-1) (Sica and Mantovani, 2012;Butoi et al, 2016;Hesketh et al, 2017) to stimulate endothelial cell morphogenesis and activation (Kalucka et al, 2017). Macrophages are extremely diverse and plastic cells, and their phenotypic subset is determined by environmental signals (Murray, 2017).…”

Section: Introductionmentioning

confidence: 99%

Engineering Immunomodulatory Biomaterials for Regenerating the Infarcted Myocardium

Bloise

Rountree

Polucha

et al. 2020

Front. Bioeng. Biotechnol.

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Coronary artery disease is a severe ischemic condition characterized by the reduction of blood flow in the arteries of the heart that results in the dysfunction and death of cardiac tissue. Despite research over several decades on how to reduce long-term complications and promote angiogenesis in the infarct, the medical field has yet to define effective treatments for inducing revascularization in the ischemic tissue. With this work, we have developed functional biomaterials for the controlled release of immunomodulatory cytokines to direct immune cell fate for controlling wound healing in the ischemic myocardium. The reparative effects of colony-stimulating factor (CSF-1), and anti-inflammatory interleukins 4/6/13 (IL4/6/13) have been evaluated in vitro and in a predictive in vivo model of ischemia (the skin flap model) to optimize a new immunomodulatory biomaterial that we use for treating infarcted rat hearts. Alginate hydrogels have been produced by internal gelation with calcium carbonate (CaCO 3) as carriers for the immunomodulatory cues, and their stability, degradation, rheological properties and release kinetics have been evaluated in vitro. CD14 positive human peripheral blood monocytes treated with the immunomodulatory biomaterials show polarization into pro-healing macrophage phenotypes. Unloaded and CSF-1/IL4 loaded alginate gel formulations have been implanted in skin flap ischemic wounds to test the safety and efficacy of the delivery system in vivo. Faster wound healing is observed with the new therapeutic treatment, compared to the wounds treated with the unloaded controls at day 14. The optimized therapy has been evaluated in a rat model of myocardial infarct (ischemia/reperfusion). Macrophage polarization toward healing phenotypes and global cardiac function measured with echocardiography and immunohistochemistry at 4 and 15 days demonstrate the therapeutic potential of the proposed immunomodulatory treatment in a clinically relevant infarct model.

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“…These inflammatory processes can also induce activation of the endothelium (e.g., to cells in the near surrounding the vascular implant) and result in a shift towards the prothrombotic and proinflammatory phenotype . However, our understanding of many of these interlinked processes is still fragmented and subject of a recent research . Among other aspects, the contribution of neutrophil extracellular trap formation on thrombus growth is subject of recent research …”

Section: Characterization Of the Blood–materials Interactionsmentioning

confidence: 99%

In Vitro Thrombogenicity Testing of Biomaterials

Braune

Latour

Reinthaler

et al. 2019

Adv Healthcare Materials

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reliable, and reproducible. [20][21][22] This is, not least, important for realizing interstudy comparisons of the thrombogenicity of different materials. According, e.g., to the regulation (EU) 2017/745 of the European parliament and of the council on medical devices, in vitro and in vivo tests are a mandatory parts within the preclinical product verification and validation (see Annex II: Technical documentation, 6.1 Preclinical and clinical data). [23] Beyond the results of these tests, also detailed information concerning the test design, respective protocols and data analysis are obligatory to meet the requirements of the regulation, particularly those formulated in the ISO standard 10993 Part 4. [24,25] Since the regulatory agencies provide recommendations rather than protocols or standard operation procedures, accepted standardizations regarding the preanalytical handling of the blood, test conditions, test parameters, reference materials, static or dynamic conditions, flow conditions, and finally, which type of cells and donors should be included is lacking. Also, standard operating procedures how the testing should be performed are lacking. [9] This has led to a situation that laboratories perform in vitro assays under substantially different test conditions, including the preanalytical characterization of blood samples, the application of blood from different species, varying anticoagulation and stabilization or storage times as well as test setups. Taking these variations into account, interlaboratory or interstudy comparisons are impossible. [8,[26][27][28] Here, we review described test methods and procedures for the assessment of the thrombogenicity of materials, prerequisites for a reproducible in vitro testing, applied test system and test parameters for the characterization of the interaction of blood components/cells and the implant. We further review and outline recent approaches that may support realizing reliable, reproducible, and laboratory independent tests.

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Interaction of endothelial cells with macrophages—linking molecular and metabolic signaling

Cited by 41 publications

References 94 publications

Role of glutamine and interlinked asparagine metabolism in vessel formation

Role of glutamine and interlinked asparagine metabolism in vessel formation

Engineering Immunomodulatory Biomaterials for Regenerating the Infarcted Myocardium

In Vitro Thrombogenicity Testing of Biomaterials

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