scholarly journals COVID-19 and Hypercoagulability: A Review

2020 ◽  
Vol 26 ◽  
pp. 107602962096285
Author(s):  
Asim Kichloo ◽  
Kirk Dettloff ◽  
Michael Aljadah ◽  
Michael Albosta ◽  
Shakeel Jamal ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Treatment Strategies ◽  
Coagulation Cascade ◽  
Vascular Endothelial ◽  
The Novel ◽  
High Incidence ◽  
Thrombotic Complications ◽  
Novel Coronavirus

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.

The hallmarks of severe pulmonary arterial hypertension: the cancer hypothesis—ten years later

2020 ◽  
Vol 318 (6) ◽  
pp. L1115-L1130 ◽  
Author(s):  
Carlyne D. Cool ◽  
Wolfgang M. Kuebler ◽  
Harm Jan Bogaard ◽  
Edda Spiekerkoetter ◽  
Mark R. Nicolls ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Treatment Strategies ◽  
Vascular Wall ◽  
Vascular Endothelial ◽  
Proliferating Cells ◽  
Bone Marrow Derived Cells ◽  
Pulmonary Arterial

Severe forms of pulmonary arterial hypertension (PAH) are most frequently the consequence of a lumen-obliterating angiopathy. One pathobiological model is that the initial pulmonary vascular endothelial cell injury and apoptosis is followed by the evolution of phenotypically altered, apoptosis-resistant, proliferating cells and an inflammatory vascular immune response. Although there may be a vasoconstrictive disease component, the increased pulmonary vascular shear stress in established PAH is caused largely by the vascular wall pathology. In this review, we revisit the “quasi-malignancy concept” of severe PAH and examine to what extent the hallmarks of PAH can be compared with the hallmarks of cancer. The cancer model of severe PAH, based on the growth of abnormal vascular and bone marrow-derived cells, may enable the emergence of novel cell-based PAH treatment strategies.

scholarly journals Fundamentals in Covid-19-Associated Thrombosis: Molecular and Cellular Aspects

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniella M. Mizurini ◽  
Eugenio D. Hottz ◽  
Patrícia T. Bozza ◽  
Robson Q. Monteiro
Keyword(s):  
Laboratory Finding ◽  
Coagulation Cascade ◽  
The Novel ◽  
Cellular Mechanisms ◽  
Complex Process ◽  
High Incidence ◽  
Novel Coronavirus ◽  
Plasma Factors ◽  
Common Laboratory ◽  
Pro Inflammatory Cytokines

The novel coronavirus disease (COVID-19) is associated with a high incidence of coagulopathy and venous thromboembolism that may contribute to the worsening of the clinical outcome in affected patients. Marked increased D-dimer levels are the most common laboratory finding and have been repeatedly reported in critically ill COVID-19 patients. The infection caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is followed by a massive release of pro-inflammatory cytokines, which mediate the activation of endothelial cells, platelets, monocytes, and neutrophils in the vasculature. In this context, COVID-19-associated thrombosis is a complex process that seems to engage vascular cells along with soluble plasma factors, including the coagulation cascade, and complement system that contribute to the establishment of the prothrombotic state. In this review, we summarize the main findings concerning the cellular mechanisms proposed for the establishment of COVID-19-associated thrombosis.

scholarly journals Microparticulate Caspase 1 Regulates Gasdermin D and Pulmonary Vascular Endothelial Cell Injury

2018 ◽  
Vol 59 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Srabani Mitra ◽  
Matthew Exline ◽  
Fabien Habyarimana ◽  
Mikhail A. Gavrilin ◽  
Paul J. Baker ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Injury ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Injury ◽  
Caspase 1

Hemorrhagic complications of а novel coronavirus infection: actual clinical problem.

2021 ◽  
Author(s):  
И.Б. Симарова ◽  
С.Н. Переходов ◽  
А.Ю. Буланов
Keyword(s):  
Case Reports ◽  
Clinical Problem ◽  
Clear Understanding ◽  
The Novel ◽  
Hemorrhagic Events ◽  
Thrombotic Complications ◽  
Predictive Role ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Therapeutic Doses

Гиперкоагуляционный характер коагулопатии, ассоциированной с новой коронавирусной инфекцией COVID-19, и высокий риск связанных с этим тромботических осложнений — хорошо известный факт на сегодняшний день. Тем не менее в литературе имеются описания и геморрагических событий у больных COVID. В обзоре приведен анализ публикаций, описывающих кровотечения при коронавирусной инфекции; общая частота их в среднем составляет 4–8%. Превалируют желудочно-кишечные кровотечения, существенную часть составляют межмышечные гематомы и кровоизлияния в кожу и слизистые. Показана предиктивная роль применения антикоагулянтов в терапевтических дозах и гипофибриногенемии. Отмечено отсутствие четкого понимания патофизиологических механизмов. Hypercoagulable character of coagulopathy associated with the novel coronavirus infection COVID-19, and the high risk of associated thrombotic complications is a well-known fact. However, there are also case reports of hemorrhagic events in COVID patients in the literature. The review summarizes the publications describing bleedings in coronavirus infection; their overall frequency is on average 4–8%. Gastrointestinal bleeding are prevalent, intermuscular hematomas and hemorrhages in the skin and mucous membranes are frequent. The predictive role of anticoagulants use in therapeutic doses and hypofibrinogenemia is shown. The absence of clear understanding of the pathophysiological mechanisms is noted.

scholarly journals Blocking the REDD1/TXNIP axis ameliorates LPS-induced vascular endothelial cell injury through repressing oxidative stress and apoptosis

2019 ◽  
Vol 316 (1) ◽  
pp. C104-C110 ◽  
Author(s):  
Xuhui Hou ◽  
Songbai Yang ◽  
Jian Yin
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Reactive Oxygen Species Generation ◽  
Vascular Endothelial ◽  
Interacting Protein ◽  
Endothelial Cell Injury ◽  
Lactate Dehydrogenase Release

The aim of the present study was to investigate the potential role of regulated in development and DNA damage response 1 (REDD1) in LPS-induced vascular endothelial injury by using human umbilical vein endothelial cells (HUVECs). We observed that REDD1 expression was apparently elevated in HUVECs after exposure to LPS. Additionally, elimination of REDD1 strikingly attenuated the secretion of the proinflammatory cytokines TNF-α, IL-6, IL-1β, and monocyte chemotactic protein-1 and the endothelial cell adhesion markers ICAM-1 and VCAM-1 that was induced by LPS stimulation. Subsequently, knockdown of REDD1 augmented cell viability but ameliorated lactate dehydrogenase release in HUVECs stimulated with LPS. Meanwhile, depletion of REDD1 effectively restricted LPS-induced HUVEC apoptosis, as exemplified by reduced DNA fragmentation, and it also elevated antiapoptotic Bcl-2 protein, concomitant with reduced levels of proapoptotic proteins Bax and cleaved caspase-3. Furthermore, repression of REDD1 remarkably alleviated LPS-triggered intracellular reactive oxygen species generation accompanied by decreased malondialdehyde content and increased the activity of the endogenous antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. Most important, depletion of REDD1 protected HUVECs against inflammation-mediated apoptosis and oxidative damage partly through thioredoxin-interacting protein (TXNIP). Collectively, these findings indicate that blocking the REDD1/TXNIP axis repressed the inflammation-mediated vascular injury process, which may be closely related to oxidative stress and apoptosis in HUVECs, implying that the REDD1/TXNIP axis may be a new target for preventing the endothelial cell injury process.

scholarly journals SMARCB1 Promotes Ubiquitination and Degradation of NR4A3 via Direct Interaction Driven by ROS in Vascular Endothelial Cell Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Bingzheng Lu ◽  
Zhu Zhu ◽  
Longxiang Sheng ◽  
Yuan Li ◽  
Yang Yang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Protein Level ◽  
Cell Injury ◽  
Pathological Condition ◽  
Vascular Endothelial Cell ◽  
Direct Interaction ◽  
Glucose Deprivation ◽  
Transcriptional Level ◽  
Protein Abundance ◽  
Vascular Endothelial

Nuclear receptor subfamily 4 group A member 3 (NR4A3) protects the vascular endothelial cell (VEC) against hypoxia stress, whose expression is primarily reported to be governed at a transcriptional level. However, the regulation of NR4A3 in the protein level is largely unknown. Here, we report that NR4A3 protein abundance is decreased immensely in VEC injury induced by reoxygenation after oxygen-glucose deprivation (OGD-R), which is significantly blocked by the administration of the antioxidative steroid TRIOL. Moreover, the notable improvement of NR4A3 and the alleviation of pulmonary endothelial barrier hyperpermeability induced by acute hypobaric hypoxia in cynomolgus monkeys are also observed after TRIOL administration. The overproduction of reactive oxygen species (ROS) decreases NR4A3 protein abundance in VEC under OGD-R condition, which is reversed by TRIOL and N-acetylcysteine (NAC). TRIOL dose-dependently increases the NR4A3 protein level by inhibiting ubiquitination and ubiquitin proteasome system- (UPS-) mediated degradation rather than promoting its transcription. Using yeast two-hybrid screening, we further identify the interaction between NR4A3 and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and the DNA-binding domain of NR4A3 is required for this interaction. Knockdown of SMARCB1 reduces ubiquitination and degradation of NR4A3, suggesting the proubiquitylation effect of this interaction which is enhanced by ROS in VEC injury induced by OGD-R. In summary, our study here for the first time reveals a posttranslational regulation in SMARCB1-mediated NR4A3 protein degradation which is driven by ROS, providing further understanding of the impaired regulation of NR4A3-mediated prosurvival pathways under pathological condition in VEC.

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