A Nuclear Attack on Thrombosis and Inflammation

Conway, Edward M.

doi:10.1161/atvbaha.115.306979

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…32 Thrombomodulin exerts a potent anticoagulation effect by binding to thrombin, which directly decrease the levels of circulating thrombin, and it also inactivates factors Va and VIIIa by potentiating the generation of activated protein C. 33 Thrombomodulin protects ECs and vasculature by depressing inflammatory injuries. 34 Elevation of circulating thrombomodulin via directly delivering recombinant thrombomodulin attenuated thrombotic inflammation in experimental animals and improved clinical outcomes in patients with sepsis and suspected disseminated intravascular coagulation.…”

Section: Thrombomodulinmentioning

confidence: 99%

Thrombotic Regulation From the Endothelial Cell Perspectives

Wang

Hao

Leeper

et al. 2018

ATVB

121

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Section: Thrombomodulinmentioning

confidence: 99%

Thrombotic Regulation From the Endothelial Cell Perspectives

Wang

Hao

Leeper

et al. 2018

ATVB

121

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“…6 Different antithrombotic mechanisms are present on endothelial cells; one is the expression of tissue factor pathway inhibitor-beta (TFPIbeta) that binds both activated Factor VII and activated Factor X thus inhibiting the capacity of tissue factor to activate coagulation (Figure 3). Thrombomodulin (THBD) is highly expressed by endothelial cells, 7 and possesses an anti-thrombotic activity consisting in the upregulation of activated protein C and catalysis of thrombin inhibition by antithrombin 8,9 (Figure 3).…”

Section: Primary Hemostasismentioning

confidence: 99%

The complement alternative pathway and hemostasis

Noris

Galbusera

2022

Immunological Reviews

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The complement and hemostatic systems are complex systems, and both involve enzymatic cascades, regulators, and cell components-platelets, endothelial cells, and immune cells. The two systems are ancestrally related and are defense mechanisms that limit infection by pathogens and halt bleeding at the site of vascular injury.Recent research has uncovered multiple functional interactions between complement and hemostasis. On one side, there are proteins considered as complement factors that activate hemostasis, and on the other side, there are coagulation proteins that modulate complement. In addition, complement and coagulation and their regulatory proteins strongly interact each other to modulate endothelial, platelet and leukocyte function and phenotype, creating a potentially devastating amplifying system that must be closely regulated to avoid unwanted damage and\or disseminated thrombosis.In view of its ability to amplify all complement activity through the C3b-dependent amplification loop, the alternative pathway of complement may play a crucial role in this context. In this review, we will focus on available and emerging evidence on the role of the alternative pathway of complement in regulating hemostasis and vice-versa, and on how dysregulation of either system can lead to severe thromboinflammatory events.

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Inflammatory Mechanisms Contributing to Endothelial Dysfunction

et al. 2021

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Maintenance of endothelial cell integrity is an important component of human health and disease since the endothelium can perform various functions including regulation of vascular tone, control of hemostasis and thrombosis, cellular adhesion, smooth muscle cell proliferation, and vascular inflammation. Endothelial dysfunction is encompassed by complex pathophysiology that is based on endothelial nitric oxide synthase uncoupling and endothelial activation following stimulation from various inflammatory mediators (molecular patterns, oxidized lipoproteins, cytokines). The downstream signaling via nuclear factor-κB leads to overexpression of adhesion molecules, selectins, and chemokines that facilitate leukocyte adhesion, rolling, and transmigration to the subendothelial space. Moreover, oscillatory shear stress leads to pro-inflammatory endothelial activation with increased monocyte adhesion and endothelial cell apoptosis, an effect that is dependent on multiple pathways and flow-sensitive microRNA regulation. Moreover, the role of neutrophil extracellular traps and NLRP3 inflammasome as inflammatory mechanisms contributing to endothelial dysfunction has recently been unveiled and is under further investigation. Consequently, and following their activation, injured endothelial cells release inflammatory mediators and enter a pro-thrombotic state through activation of coagulation pathways, downregulation of thrombomodulin, and an increase in platelet adhesion and aggregation owing to the action of von-Willebrand factor, ultimately promoting atherosclerosis progression.

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A Nuclear Attack on Thrombosis and Inflammation

Cited by 3 publications

References 29 publications

Thrombotic Regulation From the Endothelial Cell Perspectives

Thrombotic Regulation From the Endothelial Cell Perspectives

The complement alternative pathway and hemostasis

Inflammatory Mechanisms Contributing to Endothelial Dysfunction

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