scholarly journals COVID-19, Pre-Eclampsia, and Complement System

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiara Agostinis ◽  
Alessandro Mangogna ◽  
Andrea Balduit ◽  
Azin Aghamajidi ◽  
Giuseppe Ricci ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Organ Failure ◽  
Inflammatory Reaction ◽  
Complement System ◽  
Normal Pregnancy ◽  
Vascular Integrity ◽  
Treatment Regimens ◽  
Virus C

COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.

160. THE ROLE OF PHAGOCYTOSIS OF APOPTOTIC SYNCYTIAL KNOTS IN THE PREVENTION OF ENDOTHELIAL CELL ACTIVATION: AN IMPORTANT ADAPTATION FOR NORMAL PREGNANCY

2010 ◽  
Vol 22 (9) ◽  
pp. 78
Author(s):  
Q. Chen ◽  
H. Jin ◽  
P. Stone ◽  
L. Chamley
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immune Responses ◽  
Cell Activation ◽  
Normal Pregnancy ◽  
Cytochalasin D ◽  
Endothelial Cell Activation ◽  
Endothelial Cell Surface ◽  
Large Numbers

Preeclampsia is characterised by an exaggerated inflammatory response and maternal endothelial cell activation. Syncytial knots, dead multinucleated fetal cells shed from the placenta in large numbers during all pregnancies, may be phagocytosed by maternal endothelial cells. Our previous studies showed that phagocytosis of necrotic but not apoptotic syncytial knots led to endothelial cell activation. It is known that phagocytosis of apoptotic cells leads to active tolerance of immune responses and in this study we questioned whether phagocytosis of apoptotic syncytial knots leads to suppression of the endothelial cells ability to be activated. Syncytial knots were harvested from 1st trimester placental explants. Monolayers of endothelial cells were pre-treated with apoptotic syncytial knots for 24 h. After washing, the endothelial cells were treated with the endothelial cell activators LPS, PMA, IL-6, or necrotic syncytial knots for 24 h. In some experiments the inhibitor of phagocytosis, cytochalasin D, was added into the cultures along with apoptotic syncytial knots. Endothelial cell-surface ICAM-1 was measured using cell based ELISAs. Expression of ICAM-1 by endothelial cells that had phagocytosed apoptotic syncytial knots prior to treatment with LPS, PMA, IL-6, or necrotic syncytial knots was significantly (P =/<0.003) reduced, compared to control endothelial cells that had not phagocytosed apoptotic syncytial knots. Inhibiting phagocytosis of apoptotic syncytial knots with cytochalasin D abolished this protective effect. Our data suggest phagocytosis of apoptotic syncytial knots results in the suppression of the ability of endothelial cells to be activated by a number of potent chemical activators, as well as by the physiologically relevant activator, necrotic syncytial knots. This work suggests that the release of apoptotic syncytial knots from the placenta during normal pregnancy may be a mechanism by which the fetus attempts to protect the maternal vasculature against activation.

THE ROLE OF INFLAMMATION AND ENDOTHELIAL CELL ACTIVATION IN HYPERTENSIVE CHILDREN WITH ENDOTHELIAL DYSFUNCTION

2011 ◽  
Vol 29 ◽  
pp. e337
Author(s):  
M. Andor ◽  
O. Margineanu ◽  
M. Tomescu ◽  
D. Lighezan ◽  
R. Christodorescu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cell Activation ◽  
Endothelial Cell Activation

scholarly journals Modulation of VEGFR-2–mediated endothelial-cell activity by VEGF-C/VEGFR-3

Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1367-1374 ◽  
Author(s):  
Kazuyoshi Matsumura ◽  
Masanori Hirashima ◽  
Minetaro Ogawa ◽  
Hajime Kubo ◽  
Hiroshi Hisatsune ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cellular Level ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Vascular Integrity ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3), a receptor for VEGF-C, was shown to be essential for angiogenesis as well as for lymphangiogenesis. Targeted disruption of theVEGFR-3 gene in mice and our previous study using an antagonistic monoclonal antibody (MoAb) for VEGFR-3 suggested that VEGF-C/VEGFR-3 signals might be involved in the maintenance of vascular integrity. In this study we used an in vitro embryonic stem (ES) cell culture system to maintain the VEGFR-3+ endothelial cell (EC) and investigated the role of VEGFR-3 signals at the cellular level. In this system packed clusters of ECs were formed. Whereas addition of exogenous VEGF-A induced EC dispersion, VEGF-C, which can also stimulate VEGFR-2, promoted EC growth without disturbing the EC clusters. Moreover, addition of AFL4, an antagonistic MoAb for VEGFR-3, resulted in EC dispersion. Cytological analysis showed that VEGF-A– and AFL4-treated ECs were indistinguishable in many aspects but were distinct from the cytological profile induced by antagonistic MoAb for VE-cadherin (VECD-1). As AFL4- induced EC dispersion requires VEGF-A stimulation, it is likely that VEGFR-3 signals negatively modulate VEGFR-2. This result provides new insights into the involvement of VEGFR-3 signals in the maintenance of vascular integrity through modulation of VEGFR-2 signals. Moreover, our findings suggest that the mechanisms underlying AFL4-induced EC dispersion are distinct from those underlying VECD-1–induced dispersion for maintenance of EC integrity.

Endothelial senescence and microRNA

2012 ◽  
Vol 3 (3) ◽  
pp. 213-223 ◽  
Author(s):  
Munekazu Yamakuchi
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cellular Senescence ◽  
Vascular Diseases ◽  
Cell Senescence ◽  
Factors Affecting ◽  
New Treatments

AbstractCellular senescence occurs when cells lose the ability to divide and proliferate. Endothelial cell senescence is associated with vascular diseases, such as atherosclerosis. In this review, I discuss the factors affecting endothelial cell senescence. Then I describe the role of microRNAs (miRNAs) in endothelial cell senescence. Understanding miRNA pathways in endothelial senescence may lead to new treatments for endothelial dysfunction and atherosclerosis.

Anthracycline-Induced Cardiotoxicity: The Role of Endothelial Dysfunction

Cardiology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Elena V. Grakova ◽  
Sergey N. Shilov ◽  
Kristina V. Kopeva ◽  
Ekaterina N. Berezikova ◽  
Anna A. Popova ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Genetic Factors ◽  
Vascular Toxicity ◽  
Endothelin 1 ◽  
Endothelial Cell Death ◽  
Endothelial Nitric Oxide ◽  
Genetic Susceptibility Factor

Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases.

scholarly journals Secretory placental factors influence to endothelial cells EA.hy926 proliferation

2012 ◽  
Vol 61 (5) ◽  
pp. 80-84
Author(s):  
Olga Igorevna Stepanova ◽  
Kseniya Nikolayevna Furayeva ◽  
Igor Pavlovic Nikolayenkov ◽  
Sergey Alekseyevich Selkov ◽  
Dmitriy Igorevich Sokolov
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Normal Pregnancy ◽  
Endothelial Cell Proliferation

We investigated the influence of placental secretory factors on endothelial cell proliferation during normal and preeclamptic pregnancy. Preeclamptic pregnancy placental factors inhibited proliferation of endothelial cells EA.hy926 in comparison with normal pregnancy placental factors. This data testify to the role of secretory placental factors in endothelial disfunction induction during preeclamptic pregnancy

scholarly journals Endothelial Dysfunction and Extra-Articular Neurological Manifestations in Rheumatoid Arthritis

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 81
Author(s):  
Jessica Maiuolo ◽  
Carolina Muscoli ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Microvascular Disease ◽  
Cell Integrity ◽  
Nutritional Interventions ◽  
Disease States ◽  
Inflammatory Autoimmune Disease ◽  
Global Population

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that affects about 1% of the global population, with a female–male ratio of 3:1. RA preferably affects the joints, with consequent joint swelling and deformities followed by ankylosis. However, evidence has accumulated showing that patients suffering from RA can also develop extra-articular manifestations, including cardiovascular disease states, neuropathies, and multiorgan dysfunction. In particular, peripheral nerve disorders showed a consistent impact in the course of the disease (prevalence about 20%) mostly associated to vasculitis of the nerve vessels leading to vascular ischemia, axonal degeneration, and neuronal demyelination. The pathophysiological basis of this RA-associated microvascular disease, which leads to impairment of assonal functionality, is still to be better clarified. However, endothelial dysfunction and alterations of the so-called brain-nerve barrier (BNB) seem to play a fundamental role. This review aims to assess the potential mechanisms underlying the impairment of endothelial cell functionality in the development of RA and to identify the role of dysfunctional endothelium as a causative mechanism of extra-articular manifestation of RA. On the other hand, the potential impact of lifestyle and nutritional interventions targeting the maintenance of endothelial cell integrity in patients with RA will be discussed as a potential option when approaching therapeutic solutions in the course of the disease.

scholarly journals Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4742-4752 ◽  
Author(s):  
Femke Zwerts ◽  
Florea Lupu ◽  
Astrid De Vriese ◽  
Saskia Pollefeyt ◽  
Lieve Moons ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Neural Tube ◽  
Heart Development ◽  
Neural Tube Closure ◽  
Endocardial Cushions ◽  
Vascular Integrity ◽  
Apoptosis Protein ◽  
Mesenchymal Transformation ◽  
Tube Closure

Abstract We explored the physiologic role of endothelial cell apoptosis during development by generating mouse embryos lacking the inhibitor of apoptosis protein (IAP) survivin in endothelium. This was accomplished by intercrossing survivinlox/lox mice with mice expressing cre recombinase under the control of the endothelial cell specific tie1 promoter (tie1-cre mice). Lack of endothelial cell survivin resulted in embryonic lethality. Mutant embryos had prominent and diffuse hemorrhages from embryonic day 9.5 (E9.5) and died before E13.5. Heart development was strikingly abnormal. Survivin-null endocardial lineage cells could not support normal epithelial-mesenchymal transformation (EMT), resulting in hypoplastic endocardial cushions and in utero heart failure. In addition, 30% of mutant embryos had neural tube closure defects (NTDs) that were not caused by bleeding or growth retardation, but were likely due to alterations in the release of soluble factors from endothelial cells that otherwise support neural stem cell proliferation and neurulation. Thus, regulation of endothelial cell survival, and maintenance of vascular integrity by survivin are crucial for normal embryonic angiogenesis, cardiogenesis, and neurogenesis.

scholarly journals Hantavirus Pulmonary Syndrome-Associated Hantaviruses Contain Conserved and Functional ITAM Signaling Elements

2003 ◽  
Vol 77 (2) ◽  
pp. 1638-1643 ◽  
Author(s):  
Erika Geimonen ◽  
Rachel LaMonica ◽  
Karen Springer ◽  
Yildiz Farooqui ◽  
Irina N. Gavrilovskaya ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Hemorrhagic Fever ◽  
Hantavirus Pulmonary Syndrome ◽  
Hybrid Analysis ◽  
Vascular Integrity ◽  
Cell Functions ◽  
Cell Responses ◽  
Two Hybrid

ABSTRACT Hantaviruses infect human endothelial and immune cells, causing two human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). We have identified key signaling elements termed immunoreceptor tyrosine-based activation motifs (ITAMs) within the G1 cytoplasmic tail of all HPS-causing hantaviruses. ITAMs direct receptor signaling within immune and endothelial cells and the presence of ITAMs in all HPS-causing hantaviruses provides a means for altering normal cellular responses which maintain vascular integrity. The NY-1 G1 ITAM was shown to coprecipitate a complex of phosphoproteins from cells, and the G1 ITAM is a substrate for the Src family kinase Fyn. The hantavirus ITAM coprecipitated Lyn, Syk, and ZAP-70 kinases from T or B cells, while mutagenesis of the ITAM abolished these interactions. In addition, G1 ITAM tyrosines directed intracellular interactions with Syk by mammalian two-hybrid analysis. These findings demonstrate that G1 ITAMs bind key cellular kinases that regulate immune and endothelial cell functions. There is currently no means for establishing the role of the G1 ITAM in hantavirus pathogenesis. However, the conservation of G1 ITAMs in all HPS-causing hantaviruses and the role of these signaling elements in immune and endothelial cells suggest that functional G1 ITAMs are likely to dysregulate normal immune and endothelial cell responses and contribute to hantavirus pathogenesis.

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