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16 pages, 1679 KiB

Open AccessArticle

Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis

by Amal Kouadri, Johanna Cormenier, Kevin Gemy, Laurence Macari, Peggy Charbonnier, Pierre Richaud, Isabelle Michaud-Soret, Nadia Alfaidy and Mohamed Benharouga

Biomedicines 2021, 9(4), 329; https://doi.org/10.3390/biomedicines9040329 - 24 Mar 2021

Cited by 7 | Viewed by 2801

Abstract

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF Transmembrane Conductance Regulator (CFTR), an apical chloride channel. An early inflammation (EI) in the lung of CF patients occurring in the absence of any bacterial infection has been reported. This [...] Read more.

Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF Transmembrane Conductance Regulator (CFTR), an apical chloride channel. An early inflammation (EI) in the lung of CF patients occurring in the absence of any bacterial infection has been reported. This EI has been proposed to be associated with oxidative stress (OX-S), generated by deregulations of the oxidant/antioxidant status. Recently, we demonstrated that copper (Cu), an essential trace element, mediates OX-S in bronchial cells. However, the role of this element in the development of CF-EI, in association with OX-S, has never been investigated. Using healthy (16HBE14o-; HBE), CF (CFBE14o-; CFBE), and corrected-wild type CFTR CF (CFBE-wt) bronchial cells, we characterized the inflammation and OX-S profiles in relation to the copper status and CFTR expression and function. We demonstrated that CFBE cells exhibited a CFTR-independent intrinsic inflammation. These cells also exhibited an alteration in mitochondria, UPR (Unfolded Protein Response), catalase, Cu/Zn- and Mn-SOD activities, and an increase in the intracellular content of iron, zinc, and Cu. The increase in Cu concentration was associated with OX-S and inflammatory responses. These data identify cellular Cu as a key factor in the generation of CF-associated OX-S and opens new areas of investigation to better understand CF-associated EI. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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16 pages, 3282 KiB

Open AccessArticle

Evidence-Based View of Safety and Effectiveness of Prokineticin Receptors Antagonists during Pregnancy

by Deborah Reynaud, Frederic Sergent, Roland Abi Nahed, Wael Traboulsi, Constance Collet, Christel Marquette, Pascale Hoffmann, Gianfranco Balboni, Qun-Yong Zhou, Padma Murthi, Mohamed Benharouga and Nadia Alfaidy

Biomedicines 2021, 9(3), 309; https://doi.org/10.3390/biomedicines9030309 - 17 Mar 2021

Cited by 7 | Viewed by 3324

Abstract

Endocrine gland derived vascular endothelial growth factor (EG-VEGF) is a canonical member of the prokineticin (PROKs) family. It acts via the two G-protein coupled receptors, namely PROKR1 and PROKR2. We have recently demonstrated that EG-VEGF is highly expressed in the human placenta; contributes [...] Read more.

Endocrine gland derived vascular endothelial growth factor (EG-VEGF) is a canonical member of the prokineticin (PROKs) family. It acts via the two G-protein coupled receptors, namely PROKR1 and PROKR2. We have recently demonstrated that EG-VEGF is highly expressed in the human placenta; contributes to placental vascularization and growth and that its aberrant expression is associated with pregnancy pathologies including preeclampsia and fetal growth restriction. These findings strongly suggested that antagonization of its receptors may constitute a potential therapy for the pregnancy pathologies. Two specific antagonists of PROKR1 (PC7) and for PROKR2 (PKRA) were reported to reverse PROKs adverse effects in other systems. In the view of using these antagonists to treat pregnancy pathologies, a proof of concept study was designed to determine the biological significances of PC7 and PKRA in normal pregnancy outcome. PC7 and PKRA were tested independently or in combination in trophoblast cells and during early gestation in the gravid mouse. Both independent and combined treatments uncovered endogenous functions of EG-VEGF. The independent use of antagonists distinctively identified PROKR1 and PROKR2-mediated EG-VEGF signaling on trophoblast differentiation and invasion; thereby enhancing feto-placental growth and pregnancy outcome. Thus, our study provides evidence for the potential safe use of PC7 or PKRA to improve pregnancy outcome. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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18 pages, 4734 KiB

Open AccessArticle

Angiogenesis Is Differentially Modulated by Platelet-Derived Products

by Sarah Berndt, Gilles Carpentier, Antoine Turzi, Frédéric Borlat, Muriel Cuendet and Ali Modarressi

Biomedicines 2021, 9(3), 251; https://doi.org/10.3390/biomedicines9030251 - 4 Mar 2021

Cited by 10 | Viewed by 4764

Abstract

Platelet-derived preparations are being used in clinic for their role in tissue repair and regenerative processes. The release of platelet-derived products such as autologous growth factors, cytokines and chemokines can trigger therapeutic angiogenesis. In this in vitro study, we evaluated and compared the [...] Read more.

Platelet-derived preparations are being used in clinic for their role in tissue repair and regenerative processes. The release of platelet-derived products such as autologous growth factors, cytokines and chemokines can trigger therapeutic angiogenesis. In this in vitro study, we evaluated and compared the ability of three platelet-derived preparations: platelet-rich-plasma (PRP), PRP-hyaluronic acid (PRP-HA) and platelet lysates (PL) at various concentrations (5–40%) to modulate human umbilical vein endothelial cells (HUVEC) biological effects on metabolism, viability, senescence, angiogenic factors secretion and angiogenic capacities in 2D (endothelial tube formation assay or EFTA) and in 3D (fibrin bead assay or FBA). HUVEC exocytosis was stimulated with PRP and PRP-HA. Cell viability was strongly increased by PRP and PRP-HA but mildly by PL. The three preparations inhibit HUVEC tube formation on Matrigel, while PRP enhanced the complexity of the network. In the fibrin bead assay (FBA), PRP and PRP-HA stimulated all steps of the angiogenic process resulting in massive sprouting of a branched microvessel network, while PL showed a weaker angiogenic response. Secretome profiling revealed modulation of 26 human angiogenic proteins upon treatment with the platelet derived preparations. These in vitro experiments suggest that PRP and PRP-HA are effective biological therapeutic tools when sustained therapeutic angiogenesis is needed. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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14 pages, 2820 KiB

Open AccessEditor’s ChoiceArticle

Retinal Microvascular Impairment in COVID-19 Bilateral Pneumonia Assessed by Optical Coherence Tomography Angiography

by Jorge González-Zamora, Valentina Bilbao-Malavé, Elsa Gándara, Anna Casablanca-Piñera, Claudia Boquera-Ventosa, Manuel F. Landecho, Javier Zarranz-Ventura and Alfredo García-Layana

Biomedicines 2021, 9(3), 247; https://doi.org/10.3390/biomedicines9030247 - 2 Mar 2021

Cited by 49 | Viewed by 4299

Abstract

The purpose of this study was to evaluate the presence of retinal and microvascular alterations in COVID-19 patients with bilateral pneumonia due to SARS-COV-2 that required hospital admission and compare this with a cohort of age- and sex-matched controls. COVID-19 bilateral pneumonia patients [...] Read more.

The purpose of this study was to evaluate the presence of retinal and microvascular alterations in COVID-19 patients with bilateral pneumonia due to SARS-COV-2 that required hospital admission and compare this with a cohort of age- and sex-matched controls. COVID-19 bilateral pneumonia patients underwent retinal imaging 14 days after hospital discharge with structural optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) measurements. Vessel density (VD) and foveal avascular zone (FAZ) area were evaluated in the superficial, deep capillary plexus (SCP, DCP), and choriocapillaris (CC). After exclusion criteria, only one eye per patient was selected, and 50 eyes (25 patients and 25 controls) were included in the analysis. COVID-19 patients presented significantly thinner ganglion cell layer (GCL) (p = 0.003) and thicker retinal nerve fiber layer (RNFL) compared to controls (p = 0.048), and this RNFL thickening was greater in COVID-19 cases with cotton wool spots (CWS), when compared with patients without CWS (p = 0.032). In both SCP and DCP, COVID-19 patients presented lower VD in the foveal region (p < 0.001) and a greater FAZ area than controls (p = 0.007). These findings suggest that thrombotic and inflammatory phenomena could be happening in the retina of COVID-19 patients. Further research is warranted to analyze the longitudinal evolution of these changes over time as well as their correlation with disease severity. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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20 pages, 7772 KiB

Open AccessArticle

Anomalous Angiogenesis in Retina

by Rocío Vega, Manuel Carretero and Luis L Bonilla

Biomedicines 2021, 9(2), 224; https://doi.org/10.3390/biomedicines9020224 - 22 Feb 2021

Cited by 9 | Viewed by 4290

Abstract

Age-related macular degeneration (AMD) may cause severe loss of vision or blindness, particularly in elderly people. Exudative AMD is characterized by the angiogenesis of blood vessels growing from underneath the macula, crossing the blood–retina barrier (which comprises Bruch’s membrane (BM) and the retinal [...] Read more.

Age-related macular degeneration (AMD) may cause severe loss of vision or blindness, particularly in elderly people. Exudative AMD is characterized by the angiogenesis of blood vessels growing from underneath the macula, crossing the blood–retina barrier (which comprises Bruch’s membrane (BM) and the retinal pigmentation epithelium (RPE)), leaking blood and fluid into the retina and knocking off photoreceptors. Here, we simulate a computational model of angiogenesis from the choroid blood vessels via a cellular Potts model, as well as BM, RPE cells, drusen deposits and photoreceptors. Our results indicate that improving AMD may require fixing the impaired lateral adhesion between RPE cells and with BM, as well as diminishing Vessel Endothelial Growth Factor (VEGF) and Jagged proteins that affect the Notch signaling pathway. Our numerical simulations suggest that anti-VEGF and anti-Jagged therapies could temporarily halt exudative AMD while addressing impaired cellular adhesion, which could be more effective over a longer time-span. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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Review

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20 pages, 3825 KiB

Open AccessReview

Endothelial Barrier Function and Leukocyte Transmigration in Atherosclerosis

by Thijs J. Sluiter, Jaap D. van Buul, Stephan Huveneers, Paul H. A. Quax and Margreet R. de Vries

Biomedicines 2021, 9(4), 328; https://doi.org/10.3390/biomedicines9040328 - 24 Mar 2021

Cited by 57 | Viewed by 9261

Abstract

The vascular endothelium is a highly specialized barrier that controls passage of fluids and migration of cells from the lumen into the vessel wall. Endothelial cells assist leukocytes to extravasate and despite the variety in the specific mechanisms utilized by different leukocytes to [...] Read more.

The vascular endothelium is a highly specialized barrier that controls passage of fluids and migration of cells from the lumen into the vessel wall. Endothelial cells assist leukocytes to extravasate and despite the variety in the specific mechanisms utilized by different leukocytes to cross different vascular beds, there is a general principle of capture, rolling, slow rolling, arrest, crawling, and ultimately diapedesis via a paracellular or transcellular route. In atherosclerosis, the barrier function of the endothelium is impaired leading to uncontrolled leukocyte extravasation and vascular leakage. This is also observed in the neovessels that grow into the atherosclerotic plaque leading to intraplaque hemorrhage and plaque destabilization. This review focuses on the vascular endothelial barrier function and the interaction between endothelial cells and leukocytes during transmigration. We will discuss the role of endothelial dysfunction, transendothelial migration of leukocytes and plaque angiogenesis in atherosclerosis. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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19 pages, 1260 KiB

Open AccessReview

Cannabinoid Signalling in Immune–Reproductive Crosstalk during Human Pregnancy

by Harmeet Gurm, Jeremy A. Hirota and Sandeep Raha

Biomedicines 2021, 9(3), 267; https://doi.org/10.3390/biomedicines9030267 - 7 Mar 2021

Cited by 6 | Viewed by 3431

Abstract

Despite the intricate involvement of the endocannabinoid system in various physiological processes, it remains one of the most under-studied biological systems of the human body. The scope of endocannabinoid signalling is widespread, ranging from modulation of immune responses in innate and adaptive immunity [...] Read more.

Despite the intricate involvement of the endocannabinoid system in various physiological processes, it remains one of the most under-studied biological systems of the human body. The scope of endocannabinoid signalling is widespread, ranging from modulation of immune responses in innate and adaptive immunity to gestational processes in female physiology. Cannabinoid receptors are ubiquitously distributed in reproductive tissues and are thought to play a role in regulating the immune–reproductive interactions required for successful pregnancy, specifically among uterine natural killer cells and placental extravillous trophoblasts. The use of cannabis during pregnancy, however, can perturb endocannabinoid homeostasis through effects mediated by its major constituents,

Δ

-9-tetrahydrocannabinol and cannabidiol. Decidualization of the endometrium, invasion, and angiogenesis may be impaired as a consequence, leading to clinical complications such as miscarriage and preeclampsia. In this review, the crosstalk between endocannabinoid signalling in uterine natural killer cells and placental extravillous trophoblasts will be examined in healthy and complicated pregnancies. This lays a foundation for discussing the potential of targeting the endocannabinoid system for therapeutic benefit, particularly with regard to the emerging field of synthetic cannabinoids. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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19 pages, 1974 KiB

Open AccessReview

Role of CD146 (MCAM) in Physiological and Pathological Angiogenesis—Contribution of New Antibodies for Therapy

by Ahmad Joshkon, Xavier Heim, Cléa Dubrou, Richard Bachelier, Wael Traboulsi, Jimmy Stalin, Hussein Fayyad-Kazan, Bassam Badran, Alexandrine Foucault-Bertaud, Aurelie S. Leroyer, Nathalie Bardin and Marcel Blot-Chabaud

Biomedicines 2020, 8(12), 633; https://doi.org/10.3390/biomedicines8120633 - 19 Dec 2020

Cited by 32 | Viewed by 5081

Abstract

The fundamental role of cell adhesion molecules in mediating various biological processes as angiogenesis has been well-documented. CD146, an adhesion molecule of the immunoglobulin superfamily, and its soluble form, constitute major players in both physiological and pathological angiogenesis. A growing body of evidence [...] Read more.

The fundamental role of cell adhesion molecules in mediating various biological processes as angiogenesis has been well-documented. CD146, an adhesion molecule of the immunoglobulin superfamily, and its soluble form, constitute major players in both physiological and pathological angiogenesis. A growing body of evidence shows soluble CD146 to be significantly elevated in the serum or interstitial fluid of patients with pathologies related to deregulated angiogenesis, as autoimmune diseases, obstetric and ocular pathologies, and cancers. To block the undesirable effects of this molecule, therapeutic antibodies have been developed. Herein, we review the multifaceted functions of CD146 in physiological and pathological angiogenesis and summarize the interest of using monoclonal antibodies for therapeutic purposes. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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13 pages, 673 KiB

Open AccessReview

CD146/sCD146 in the Pathogenesis and Monitoring of Angiogenic and Inflammatory Diseases

by Xavier Heim, Ahmad Joshkon, Julien Bermudez, Richard Bachelier, Cléa Dubrou, José Boucraut, Alexandrine Foucault-Bertaud, Aurélie S. Leroyer, Francoise Dignat-George, Marcel Blot-Chabaud and Nathalie Bardin

Biomedicines 2020, 8(12), 592; https://doi.org/10.3390/biomedicines8120592 - 10 Dec 2020

Cited by 12 | Viewed by 3455

Abstract

CD146 is a cell adhesion molecule expressed on endothelial cells, as well as on other cells such as mesenchymal stem cells and Th17 lymphocytes. This protein also exists in a soluble form, whereby it can be detected in biological fluids, including the serum [...] Read more.

CD146 is a cell adhesion molecule expressed on endothelial cells, as well as on other cells such as mesenchymal stem cells and Th17 lymphocytes. This protein also exists in a soluble form, whereby it can be detected in biological fluids, including the serum or the cerebrospinal fluid (CSF). Some studies have highlighted the significance of CD146 and its soluble form in angiogenesis and inflammation, having been shown to contribute to the pathogenesis of many inflammatory autoimmune diseases, such as systemic sclerosis, mellitus diabetes, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. In this review, we will focus on how CD146 and sCD146 contribute to the pathogenesis of the aforementioned autoimmune diseases and discuss the relevance of considering it as a biomarker in these pathologies. Full article

(This article belongs to the Special Issue Angiogenesis and Inflammation in Biological Barriers)

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