scholarly journals Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19

2021 ◽  
Vol 22 (20) ◽  
pp. 11170
Author(s):  
Panagiotis Theofilis ◽  
Marios Sagris ◽  
Alexios S. Antonopoulos ◽  
Evangelos Oikonomou ◽  
Costas Tsioufis ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Endothelial Glycocalyx ◽  
Platelet Factor ◽  
Tnf Α ◽  
Thrombotic Complications ◽  
Leukocyte Aggregation ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor

Background: Atherosclerotic cardiovascular diseases are characterized by a dysregulated inflammatory and thrombotic state, leading to devastating complications with increased morbidity and mortality rates. Summary: In this review article, we present the available evidence regarding the impact of inflammation on platelet activation in atherosclerosis. Key messages: In the context of a dysfunctional vascular endothelium, structural alterations by means of endothelial glycocalyx thinning or functional modifications through impaired NO bioavailability and increased levels of von Willebrand factor result in platelet activation. Moreover, neutrophil-derived mediators, as well as neutrophil extracellular traps formation, have been implicated in the process of platelet activation and platelet-leukocyte aggregation. The role of pro-inflammatory cytokines is also critical since their receptors are also situated in platelets while TNF-α has also been found to induce inflammatory, metabolic, and bone marrow changes. Additionally, important progress has been made towards novel concepts of the interaction between inflammation and platelet activation, such as the toll-like receptors, myeloperoxidase, and platelet factor-4. The accumulating evidence is especially important in the era of the coronavirus disease-19 pandemic, characterized by an excessive inflammatory burden leading to thrombotic complications, partially mediated by platelet activation. Lastly, recent advances in anti-inflammatory therapies point towards an anti-thrombotic effect secondary to diminished platelet activation.

Effects of von Willebrand factor concentration and platelet collision on shear-induced platelet activation

2008 ◽  
Vol 100 (07) ◽  
pp. 60-68 ◽  
Author(s):  
Zhenyue Gao ◽  
Fang Liu ◽  
Ziqiang Yu ◽  
Xia Bai ◽  
Fengyuan Zhuang ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Von Willebrand Factor ◽  
Annexin V ◽  
Flow Chamber ◽  
Platelet Glycoprotein ◽  
High Shear ◽  
Shear Rates ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor

SummaryThe binding of plasma von Willebrand factor (vWF) to platelet glycoprotein (GP) Ibα in a high shear stress field, and subsequent integrin-GPIIb/IIIa-vWF conjunction induces platelet aggregation (SIPA). However, the specific biomechanical mechanism of the vWF-GPIb interaction still remains to be elucidated. A parallel-plate rectangular flow chamber was built to simulate a stenopeic artery flow pattern. Using the flow chamber, we examined shear- induced platelet activation (SIPAct) at different vWF concentrations (5–25 µg/ml) and several simulated stenotic high shear rates. P-selectin expression on the platelets and annexin V binding to the platelets were used as two markers of platelet activation. At different localized shear rates (3,000 s-1–9,500 s-1), the percentage of annexin V and P-selectin positive cells increased from 8.3 ± 0.4% to 22.3 ± 1.8% ( p 0.05) and from 17.4 ± 0.5% to 33.5 ± 2.5% (p 0.05),respectively. As the vWF concentration increased from 5 µg/ml to 25 µg/ml, the annexinV binding rate increased from 7.2 ± 0.6% to 53.4 ± 3.8% (p 0.05), and P-selectin expression increased from 16.5 ± 1.2% to 65.9 ± 5.2% (p 0.05). A test in a uniform shear field using cone-plate viscometer rheometry showed that the platelet activation rate was proportional to the platelet concentration. This result suggests that platelet collision is one of the impact factors of SIPAct.

Post-DDAVP Thrombocytopenia in Type 2B von Willebrand Disease Is not Associated with Platelet Consumption: Failure to Demonstrate Glycocalicin Increase or Platelet Activation

1999 ◽  
Vol 81 (02) ◽  
pp. 224-228 ◽  
Author(s):  
A. Steffan ◽  
E. Pontara ◽  
A. Zucchetto ◽  
C. Rossi ◽  
L. De Marco ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Surface Expression ◽  
Von Willebrand Disease ◽  
Platelet Surface ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Thrombotic Complications ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThrombocytopenia is frequently reported in type 2B von Willebrand disease (vWD), and thought to be related to the abnormally high affinity of 2B von Willebrand factor (vWF) for platelet GPIb-IX. To gain an insight into the nature of this thrombocytopenia, we measured plasma glycocalicin (GC) levels (as a marker of platelet turnover), and platelet surface expression of the alpha granule protein P-selectin (as a marker of platelet activation) in 9 patients with type 2B vWD before, and in 4 patients also following the infusion of 1-desamino-8-d-arginine vasopressin (DDAVP). Three patients presented a persistent decrease of platelet counts in the resting condition. GC levels were within the normal range, regardless of the platelet counts, in all but one patient who presented, on the other hand, a normal platelet count. Moreover, platelets expressed normal amounts of P-selectin on their surface, regardless of platelet counts. These findings suggest that the thrombocytopenia observed in type 2B vWD is not due to platelet activation and subsequent consumption in circulation.Despite a significant, albeit transient, decrease in platelet count, DDAVP did not induce an increase in plasma GC levels, nor enhance P-selectin expression. These observations indicate that the acute post-DDAVP thrombocytopenia in type 2B vWD is not related to platelet activation and consumption. We advance that the post-DDAVP 2B vWF is hemostatically more active, and able to induce agglutination but not aggregation of circulating platelets. This would explain both the prompt recovery of basal platelet counts after the post-DDAVP decrease, and the lack of reported thrombotic complications in this disorder.Therefore, even though 2B vWF is characterized by an enhanced affinity for the platelet surface, its binding to platelet GPIb-IX in the soluble phase is not able to induce true platelet aggregation; vWF thus appears to be mainly an adhesive protein, rather than an aggregating agent.

Platelet Activation and Aggregation Induced by Recombinant von Willebrand Factors Reproducing Four Type 2B von Willebrand Disease Missense Mutations

1998 ◽  
Vol 79 (01) ◽  
pp. 211-216 ◽  
Author(s):  
Lysiane Hilbert ◽  
Claudine Mazurier ◽  
Christophe de Romeuf
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Von Willebrand Disease ◽  
Platelet Glycoprotein ◽  
Missense Mutations ◽  
Inhibit Platelet Aggregation ◽  
Wild Type ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryType 2B of von Willebrand disease (vWD) refers to qualitative variants with increased affinity of von Willebrand factor (vWF) for platelet glycoprotein Ib (GPIb). All the mutations responsible for type 2B vWD have been located in the A1 domain of vWF. In this study, various recombinant von Willebrand factors (rvWF) reproducing four type 2B vWD missense mutations were compared to wild-type rvWF (WT-rvWF) for their spontaneous binding to platelets and their capacity to induce platelet activation and aggregation. Our data show that the multimeric pattern of each mutated rvWF is similar to that of WT-rvWF but the extent of spontaneous binding and the capacity to induce platelet activation and aggregation are more important for the R543Q and V553M mutations than for the L697V and A698V mutations. Both the binding of mutated rvWFs to platelets and platelet aggregation induced by type 2B rvWFs are inhibited by monoclonal anti-GPIb and anti-vWF antibodies, inhibitors of vWF binding to platelets in the presence of ristocetin, as well as by aurin tricarboxylic acid. On the other hand, EDTA and a monoclonal antibody directed against GPIIb/IIIa only inhibit platelet aggregation. Furthermore, the incubation of type 2B rvWFs with platelets, under stirring conditions, results in the decrease in high molecular weight vWF multimers in solution, the extent of which appears correlated with that of plasma vWF from type 2B vWD patients harboring the corresponding missense mutation. This study supports that the binding of different mutated type 2B vWFs onto platelet GPIb induces various degrees of platelet activation and aggregation and thus suggests that the phenotypic heterogeneity of type 2B vWD may be related to the nature and/or location of the causative point mutation.

Partially desulfated heparin modulates the interaction between anti-protamine/heparin antibodies and platelets

2016 ◽  
Vol 115 (02) ◽  
pp. 324-332 ◽  
Author(s):  
Rabie Jouni ◽  
Heike Zöllner ◽  
Ahmad Khadour ◽  
Jan Wesche ◽  
Anne Grotevendt ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Platelet Factor ◽  
Standard Drug ◽  
Platelet Surface ◽  
Minimal Impact ◽  
Platelet Survival ◽  
Heparin Complexes ◽  
The Impact

SummaryProtamine (PRT) is the standard drug to neutralise heparin. PRT/heparin complexes induce an immune response similar to that observed in heparin-induced thrombocytopenia (HIT). Partially desulfated heparin (ODSH) was shown to interfere with anti-platelet factor 4/heparin antibodies (Abs), which are responsible for HIT. In this study, we analyse the impact of ODSH on the interaction between anti-PRT/heparin Abs and platelets. The ability of ODSH to prevent anti-PRT/heparin Ab-induced platelet destruction in vivo was investigated using the NOD/ SCID mouse model. ODSH improved platelet survival in the presence of PRT, heparin and anti-PRT/heparin Abs (median platelet survival after 300 minutes (min) with 20 μg/ml ODSH: 75 %, range 70–81 % vs without ODSH: 49%, range 44–59%, p=0.006). Furthermore, when ODSH was applied 60 min after Ab injection platelet survival was improved (median platelet survival after 300 min with ODSH: 83 %, range 77–93 % vs without ODSH: 59 %, range 29–61 %, p=0.02). In in vitro experiments ODSH inhibited platelet activation at concentrations > 16 μg/mL (p< 0.001), as well as PRT/heparin complex binding to platelets (mean fluorescence intensity [MFI] without ODSH: 85 ± 14 vs with ODSH: 15 ± 0.6, p=0.013). ODSH also displaced pre-bound complexes from the platelet surface (MFI without ODSH: 324 ± 43 vs with 32 μg/ml ODSH: 53 ± 9, p< 0.001). While interfering with platelet activation by anti-PRT/heparin Abs, up to a concentration of 16 μg/ml, ODSH had only minimal impact on neutralisation of heparin by PRT. In conclusion, our study shows that ODSH is able to inhibit platelet activation and destruction suggesting a potential clinical use to reduce anti-PRT/heparin Ab-mediated adverse effects.

Studies of α-granule proteins in cultured human megakaryocytes

2003 ◽  
Vol 90 (11) ◽  
pp. 844-852 ◽  
Author(s):  
Dragoslava Veljkovic ◽  
Elisabeth Cramer ◽  
Gulie Alimardani ◽  
Serge Fichelson ◽  
Jean-Marc Massé ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Protein Processing ◽  
Platelet Factor ◽  
Protein Storage ◽  
Granule Protein ◽  
Granule Proteins ◽  
Processing And Storage ◽  
Von Willebrand ◽  
And Storage ◽  
Willebrand Factor

Summaryα-Granule protein storage is important for producing platelets with normal haemostatic function. The low to undetectable levels of several megakaryocyte-synthesized α-granule proteins in normal plasma suggest megakaryocytes are important to sequester these proteins in vivo. α-Granule protein storage in vitrohas been studied using other cell types, with differences observed in how some proteins are processed compared to platelets. Human megakaryocytes, cultured from cord blood CD34+cells and grown in serum-free media containing thrombopoietin, were investigated to determine if they could be used as a model for studying normal α-granule protein processing and storage. ELISA indicated that cultured megakaryocytes contained the α-granule proteins multimerin, von Willebrand factor, thrombospondin-1, β-thromboglobulin and platelet factor 4, but no detectable fibrinogen and factor V. A significant proportion of the α-granule protein in megakaryocyte cultures was contained within the cells (averages: 41 – 71 %), consistent with storage. Detailed analyses of multimerin and von Willebrand factor confirmed that α-granule proteins were processed to mature forms and were predominantly located in the α-granules of cultured megakaryocytes. Thrombopoietin-stimulated cultured megakaryocytes provide a useful model for studying α-granule protein processing and storage.

scholarly journals von Willebrand factor bound to glycoprotein Ib is cleared from the platelet surface after platelet activation by thrombin

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2011-2021 ◽  
Author(s):  
P Hourdille ◽  
HR Gralnick ◽  
E Heilmann ◽  
A Derlon ◽  
AM Ferrer ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Activation ◽  
Von Willebrand Factor ◽  
Platelet Rich Plasma ◽  
Surface Expression ◽  
Von Willebrand Disease ◽  
Platelet Surface ◽  
Immunogold Staining ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract We recently reported that after activation of human platelets by thrombin, glycoprotein (GP) Ib-IX complexes are translocated to the surface-connected canalicular system (SCCS) (Blood 76:1503, 1990). As GPIb is a major receptor for von Willebrand factor (vWF) in platelet adhesion, we have now examined the consequences of thrombin activation on the organization of vWF bound to GPIb on the platelet surface. Studies were performed using monoclonal or polyclonal antibodies in either immunogold staining and electron microscopy (Au-EM) or in flow cytometry. When unstirred platelet-rich plasma was incubated with ristocetin, bound vWF was located by Au-EM as discrete masses regularly distributed over the cell surface. Platelets from a patient with Glanzmann's thrombasthenia, lacking GPIIb-IIIa complexes, gave a similar pattern, confirming that this represented binding to GPIb. That ristocetin was not precipitating vWF before their binding to the platelets was shown by the detection of similar masses on the surface of platelets of a patient with type IIB von Willebrand disease. Experiments were continued using washed normal platelets incubated in Tyrode-EDTA, the purpose of the EDTA being to limit the surface expression of endogenous vWF after platelet stimulation. Under these conditions, platelets were treated with ristocetin for 5 minutes at 37 degrees C in the presence of increasing amounts of purified vWF. This was followed by incubation with thrombin (0.5 U/mL) for periods of up to 10 minutes. Flow cytometry showed a time-dependent loss in the surface expression of vWF bound to GPIb and these changes were confirmed by Au-EM. In particular, immunogold staining performed on ultrathin sections showed that the bulk of the vWF was being cleared to internal membrane systems. Surface clearance of vWF during thrombin- induced platelet activation is a potential mechanism for regulating platelet adhesivity.

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