Thrombotic Regulation From the Endothelial Cell Perspectives

Wang, Miao; Hao, Huifeng; Leeper, Nicholas J.; Zhu, Liyuan

doi:10.1161/atvbaha.118.310367

Cited by 137 publications

(112 citation statements)

References 73 publications

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“…The function of the endothelium includes promotion of vasodilation, fibrinolysis, and anti-aggregation. Because endothelium plays a significant role in thrombotic regulation (59), hypercoagulable profiles seen in severe diseases likely indicate significant endothelial injury. Endothelial cells also express ACE2 (60,61).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

COVID-19 pathophysiology: A review

Yuki

Fujiogi

Koutsogiannaki

2020

Clinical Immunology

1,873

1,712

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Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

COVID-19 pathophysiology: A review

Yuki

Fujiogi

Koutsogiannaki

2020

Clinical Immunology

1,873

1,712

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“…The antithrombotic effect of RV is attributed to its capacity to modulate tissue factor (TF) activity and gene expression in in vitro . TF, also known as thromboplastin, is the primary initiator of the extrinsic coagulation system that triggers thrombosis by binding to and activating coagulation factor VII . TF is mainly expressed in the membranes of perivascular cells, platelets, neutrophils, and monocytes.…”

Section: Introductionmentioning

confidence: 99%

“…TF is mainly expressed in the membranes of perivascular cells, platelets, neutrophils, and monocytes. Furthermore, TF is also expressed in endothelial cells under pathophysiological conditions in response to such stimuli as tumor necrosis factor‐alpha (TNF‐α), among others. However, no studies have been conducted to integrate the actions of RV on TF activity, its protein concentration, and its mRNA expression.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Cells Deconjugate Resveratrol Metabolites to Free Resveratrol: A Possible Role in Tissue Factor Modulation

Fernández‐Castillejo

Macià

Motilva

et al. 2019

Molecular Nutrition Food Res

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Scope The antithrombotic effects of resveratrol (RV) and its derivatives remain unknown. The objective is to evaluate the modulatory effects of RV, its glucoside form, piceid, and its biological metabolites (RV‐3‐O‐β‐d‐glucuronide, RV‐4’‐O‐d‐glucuronide, and RV‐3‐O‐sulfate) on tissue factor (TF). Moreover, the endothelial metabolism of RV is assessed. Methods and results Human aortic endothelial cells (HAECs) are incubated with trans‐piceid, trans‐RV, or their biological metabolites and stimulated with tumor necrosis factor‐α (TNF‐α). TF activity, protein levels, and mRNA expression are determined in cell lysates. Moreover, RV conjugation (phase‐II‐metabolism) to its sulfated or glucuronidated metabolites and their deconjugation to their parent compound (free RV) are also assessed in cell lysates and culture media. RV decreased TF activity, protein levels, and mRNA expression, whereas piceid and RV metabolites (RVmet) had no effects. RV‐3‐O‐sulfate was the main metabolite generated in the endothelium, while RVmet are deconjugated to free RV. Isomerization of trans‐RV and its trans‐metabolites to their cis‐forms is observed. Conclusions RV exerts antithrombotic effects by modulating TF. RVmet and piceid does not exert this effect. However, the capacity of endothelial cells to deconjugate RVmet to free RV indicates that RVmet function as an endothelial reservoir for RV regeneration, thus, contributing to the antithrombotic effects of RV.

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“…This function is essential for new vessel formation to accompany growth and development, as well as for EC reshaping and migration, metabolic reprogramming and recruitment of other cells to sites of injury and inflammation . Activated EC are prothrombotic , due to the surface expression of intercellular adhesion molecules that promote platelet interaction and binding of circulating myeloid cells . Essential as this function is for control of blood flow and tissue remodelling, it needs to be reversible.…”

Section: Regulation and Regulators Of Ec Function In Different Tissuesmentioning

confidence: 99%

Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling

Reiterer

Branco

2019

The FEBS Journal

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The microvasculature is a heterogeneous, dynamic and versatile component of the systemic circulation, with a unique ability to locally self‐regulate and to respond to organ demand and environmental stimuli. Endothelial cells from different organs display considerable variation, but it is currently unclear to what extent functional properties of organ‐specific endothelial cells are intrinsic, acquired and/or reprogrammable. Vascular function is a fundamental pillar of homeostasis, and dysfunction results in systemic consequences for the organism. Additionally, vascular failure can occur downstream of organ disease or environmental stress, often driving an exacerbation of symptoms and pathologies originally independent of the local circulation. The understanding of the molecular mechanisms underlying endothelial physiology and metabolism holds the promise to inform and improve diagnosis, prognosis and treatment options for a myriad of conditions as unrelated as cancer, neurodegeneration or pulmonary hypertension, and likely everything in between, if we consider that also treatments for such conditions are primarily distributed via the bloodstream. However, studying endothelial function has its challenges: the origin, isolation, culture conditions and preconditioning stimuli make this an extremely variable cell type to study and difficult to source. Animal models exist but are neither trivial to generate, nor necessarily adequately translatable to human disease. In this article, we aim to illustrate the breadth of microvascular functions in different environments, highlighting current and pioneering studies that have advanced our insight into the importance of the integrity of this tissue, as well as the limitations posed by its heterogeneity and plasticity.

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Thrombotic Regulation From the Endothelial Cell Perspectives

Cited by 137 publications

References 73 publications

COVID-19 pathophysiology: A review

COVID-19 pathophysiology: A review

Endothelial Cells Deconjugate Resveratrol Metabolites to Free Resveratrol: A Possible Role in Tissue Factor Modulation

Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling

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