Heparan sulfate: Antithrombotic or not?

Weitz, Jeffrey I.

doi:10.1172/jci200318234

Cited by 43 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, an artificial blood vessel with EC monolayer on its inner wall is expected to inhibit thrombosis. Heparan sulfate proteoglycans (HSPGs), the main component of glycocalyx which is decorated on the surface of EC monolayer, exhibit antithrombin activity [25,26]. However, the blood compatibility of in vitro cultured ECs is poorly investigated [27].…”

Section: Platelet Adhesion On Cultured Ecsmentioning

confidence: 99%

Adhesion, Spreading, and Proliferation of Endothelial Cells on Charged Hydrogels

Chen

Yang

Gong

2009

The Journal of Adhesion

View full text Add to dashboard Cite

As soft and wet scaffolds, hydrogels are attractive materials for tissue engineering due to their similarity in structure and properties to living tissue. For designing hydrogels as potential artificial tissues, some basic requirements, such as a high level of cellular viability, suitable viscoelasticity, and high mechanical strength are required. However, it is difficult to develop a hydrogel that satisfies even two of these requirements at the same time. In this review, our recent advances in developing synthetic hydrogels as cell culture scaffold are summarized. We found that endothelial cells (ECs) can proliferate directly on some synthetic hydrogels with negatively charge, so long as the hydrogels have a Zeta potential lower than c.a. -20 mV , and the cell behavior can be controlled by adjusting the hydrogel's charge density. Furthermore, confluent EC monolayers cultured on the hydrogels show excellent platelet compatibility, compared to EC monolayer cultured on polystyrene plate. On the basis of the above study, we have further developed micro-patterned hydrogels for selective cell spreading, proliferation, and orientation. We have also developed tough hydrogels on which cells show viability. These results will promote the potential applications of synthetic hydrogels in tissue engineering.

show abstract

Section: Platelet Adhesion On Cultured Ecsmentioning

confidence: 99%

Adhesion, Spreading, and Proliferation of Endothelial Cells on Charged Hydrogels

Chen

Yang

Gong

2009

The Journal of Adhesion

View full text Add to dashboard Cite

show abstract

“…Major coagulation inhibitors include antithrombin (AT), activated protein C (APC), and tissue factor pathway inhibitor (TFPI) (34). AT circulates in the plasma at high concentration and its activity may be accelerated by heparan-sulfate (HS) proteoglycans on the EC surfaces (35). APC is produced by the complex of thrombin (also known as factor IIa) and thrombomodulin (TM) on the EC surface.…”

Section: Introductionmentioning

confidence: 99%

A Mathematical Model of Venous Thrombosis Initiation

Elizondo

Fogelson

2016

Biophysical Journal

View full text Add to dashboard Cite

We present a mathematical model for the initiation of venous thrombosis (VT) due to slow flow and the consequent activation of the endothelial cells (ECs) lining the vein, in the absence of overt mechanical disruption of the EC layer. It includes all reactions of the tissue factor (TF) pathway of coagulation through fibrin formation, incorporates the accumulation of blood cells on activated ECs, accounts for the flow-mediated delivery and removal of coagulation proteins and blood cells from the locus of the reactions, and accounts for the activity of major inhibitors including heparan-sulfate-accelerated antithrombin and activated protein C. The model reveals that the occurrence of robust thrombin generation (a thrombin burst) depends in a threshold manner on the density of TF on the activated ECs and on the concentration of thrombomodulin and the degree of heparan-sulfate accelerated antithrombin activity on those cells. Small changes in any of these in appropriate narrow ranges switches the response between ''no burst'' and ''burst.'' The model predicts synergies among the inhibitors, both in terms of each inhibitor's multiple targets, and in terms of interactions between the different inhibitors. The model strongly suggests that the rate and extent of accumulation of activated monocytes, platelets, and MPs that can support the coagulation reactions has a powerful influence on whether a thrombin burst occurs and the thrombin response when it does. The slow rate of accumulation of cells supporting coagulation is one reason that the progress of VT is so much slower than that of arterial thrombosis initiated by subendothelial exposure.

show abstract

“…105 Binding of antithrombin to endothelial cells is thought to be mediated by heparan sulfate, also a GPI-linked protein. 106 It is reduced by inflammatory markers such as interleukin (IL)-1 and tumor necrosis factor. Its deficiency may partly contribute to the hypercoagulable state in PNH, although there have been no studies exploring this.…”

mentioning

confidence: 99%

“…Only complete deficiency appears to lead to thrombosis. 106 TFPI is predominantly released by the endothelium (but is also present on the surface of monocytes, within platelets, and circulating in the plasma) and is anchored, most likely indirectly, through the GPI anchor. It is a potent anticoagulant protein that abrogates blood coagulation by inhibiting both factors Xa and the tissue factor-factor VIIa catalytic complex, making it the only physiologically active inhibitor of the initiation of blood coagulation.…”

mentioning

confidence: 99%

Thrombosis in paroxysmal nocturnal hemoglobinuria

Hill

Kelly

Hillmen

2013

Blood

389

429

View full text Add to dashboard Cite

The most frequent and feared complication of paroxysmal nocturnal hemoglobinuria (PNH) is thrombosis. Recent research has demonstrated that the complement and coagulation systems are closely integrated with each influencing the activity of the other to the extent that thrombin itself has recently been shown to activate the alternative pathway of complement. This may explain some of the complexity of the thrombosis in PNH. In this review, the recent changes in our understanding of the pathophysiology of thrombosis in PNH, as well as the treatment of thrombosis, will be discussed. Mechanisms explored include platelet activation, toxicity of free hemoglobin, nitric oxide depletion, absence of other glycosylphosphatidylinositol-linked proteins such as urokinase-type plasminogen activator receptor and endothelial dysfunction. Complement inhibition with eculizumab has a dramatic effect in PNH and has a major impact in the prevention of thrombosis as well as its management in this disease.

show abstract

Heparan sulfate: Antithrombotic or not?

Cited by 43 publications

References 18 publications

Adhesion, Spreading, and Proliferation of Endothelial Cells on Charged Hydrogels

Adhesion, Spreading, and Proliferation of Endothelial Cells on Charged Hydrogels

A Mathematical Model of Venous Thrombosis Initiation

Thrombosis in paroxysmal nocturnal hemoglobinuria

Contact Info

Product

Resources

About