Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue Factor Expression

Peshkova, Alina D.; Minh, Giang Le; Tutwiler, Valerie; Andrianova, Izabella A.; Weisel, John W.; Litvinov, Rustem I.

doi:10.1038/s41598-017-05601-9

Cited by 32 publications

(24 citation statements)

References 53 publications

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“…Once monocytes are exposed to quantities of a tissue factor, they may bind to platelets and increase MPAs 37 resulting in enhanced clot contraction to cause thrombosis. 38 In our current study, we found P-selectin expressed on the surface of platelets that interact with monocytes. However, we unexpectedly found that the numbers of circulating MPAs had no significant difference between CCS and ACS subjects.…”

Section: Discussionsupporting

confidence: 48%

The Role of ROCK in Platelet–Monocyte Collaborative Induction of Thromboinflammation during Acute Coronary Syndrome

et al. 2020

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Background Arterial thrombosis is initiated by atherosclerotic plaque damage, prothrombotic material release and platelet aggregation. Platelets are primary mediators involved in thrombosis and cooperate with vascular and immune cells. Objective Herein, we investigated how activated platelets interacted with monocytes in atherothrombosis. Methods and Results We collected patients' blood from coronary arteries during percutaneous coronary intervention and measured platelet activity. Platelets from coronary arteries had higher pseudopodium expression and activity in patients with acute coronary syndrome (ACS). Ribosome profiling of platelets from coronary blood mapped a vigorous upregulation of Rho GTPases and their downstream effectors. RhoA activated downstream Rho-associated coiled-coil containing protein kinase (ROCK), and ROCK increased surface P-selectin in coronary blood platelets. The interaction between platelets and monocytes was observed in vitro, and was found in ruptured coronary plaques of ACS. Further we found that activated platelets promoted monocytes transmigration, which could be suppressed in the presence of ROCK inhibitors. The increased surface P-selectin on thrombin-induced platelets interacted with monocytes to upregulate monocyte chemokine receptor 2 (CCR2) expression via the ROCK pathway. The expression of CCR2 was higher in monocyte–platelet aggregates than in monocytes without platelets. Finally, using the Asian Screening Array BeadChip, we identified single-nucleotide polymorphism (SNP) associated with cardiovascular events. Notably, patients having homozygous major alleles of the RHOA SNP rs11706370 presented with higher risks of cardiovascular events. Conclusion Through ROCK-activated cytoskeleton remodeling and P-selectin expression, platelets were recruited and interacted synergistically with high CCR2-expressing monocytes to induce thromboinflammation in atherothrombosis.

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Section: Discussionsupporting

confidence: 48%

The Role of ROCK in Platelet–Monocyte Collaborative Induction of Thromboinflammation during Acute Coronary Syndrome

et al. 2020

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“…There is emerging indirect evidence that the degree and the rate of contraction of clots and thrombi may be an important pathogenic factor that affects the local blood hydrodynamics and the outcome of thrombosis. 4 17 18 25 Although the severity of thrombosis is largely determined by size and location of the occluded vessel, the ability of the clot to contract more or less can largely influence the vessel cross-sectional area and consequently the blood flow through the vessel and the shear rate of the blood. This has implications for the possibility of embolization, where shear rate coupled with the structure of the clot could influence the predisposition to embolize based on either mechanical and/or enzymatic disintegration.…”

Section: Discussionmentioning

confidence: 99%

Reduced Contraction of Blood Clots in Venous Thromboembolism Is a Potential Thrombogenic and Embologenic Mechanism

Peshkova

Malyasyov

Бредихин

et al. 2018

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Contraction (retraction) of the blood clot is a part of the clotting process driven by activated platelets attached to fibrin that can potentially modulate the obstructiveness and integrity of thrombi. The aim of this work was to reveal the pathogenic importance of contraction of clots and thrombi in venous thromboembolism (VTE). We investigated the kinetics of clot contraction in the blood of 55 patients with VTE. In addition, we studied the ultrastructure of ex vivo venous thrombi as well as the morphology and functionality of isolated platelets. Thrombi from VTE patients contained compressed polyhedral erythrocytes, a marker for clot contraction in vivo. The extent and rate of contraction were reduced by twofold in clots from the blood of VTE patients compared with healthy controls. The contraction of clots from the blood of patients with pulmonary embolism was significantly impaired compared with that of those with isolated venous thrombosis, suggesting that less compacted thrombi are prone to embolization. The reduced ability of clots to contract correlated with continuous platelet activation followed by their partial refractoriness. Morphologically, 75% of platelets from VTE patients were spontaneously activated (with filopodia) compared with only 21% from healthy controls. At the same time, platelets from VTE patients showed a 1.4-fold reduction in activation markers expressed in response to chemical activation when compared with healthy individuals. The results obtained suggest that the impaired contraction of thrombi is an underappreciated pathogenic mechanism in VTE that may regulate the obstructiveness and embologenicity of venous thrombi.

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“…It has been shown in previous studies that monocytes carry TF, which is responsible for their procoagulant effect. 52 Under physiological conditions, monocytes are inactivated and do not express TF. When activated in a pathological context, they acquire TF expression.…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment and clonal monocytes from chronic myelomonocytic leukemia induce a procoagulant climate

et al. 2019

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Chronic myelomonocytic leukemia (CMML) is a myeloid hematological malignancy with overlapping features of myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). The knowledge of the role of the tumor microenvironment (TME), particularly mesenchymal stromal cells (MSCs), in MDS pathogenesis is increasing. Generally, cancer is associated with a procoagulant state participating in tumor development. Monocytes release procoagulant, tissue factor (TF)–bearing microparticles. We hypothesized that MSCs and clonal monocytes release procoagulant extracellular vesicles (EVs) within the CMML TME, inducing a procoagulant state that could modify hematopoietic stem cell (HSC) homeostasis. We isolated and cultured MSCs and monocytes from CMML patients and MSCs from healthy donors (HDs). Their medium EVs and small EVs (sEVs) were collected after iterative ultracentrifugations and characterized by nanoparticle tracking analysis. Their impact on hemostasis was studied with a thrombin generation assay and fibrinography. CMML or HD HSCs were exposed to sEVs from either CMML or HD MSCs. CMML MSC sEVs increased HD HSC procoagulant activity, suggesting a transfer of TF from the CMML TME to HD HSCs. The presence of TF on sEVs was shown by electron microscopy and western blot. Moreover, CMML monocyte EVs conferred a procoagulant activity to HD MSCs, which was reversed by an anti-TF antibody, suggesting the presence of TF on the EVs. Our findings revealed a procoagulant “climate” within the CMML environment related to TF-bearing sEVs secreted by CMML MSCs and monocytes.

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Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue Factor Expression

Cited by 32 publications

References 53 publications

The Role of ROCK in Platelet–Monocyte Collaborative Induction of Thromboinflammation during Acute Coronary Syndrome

The Role of ROCK in Platelet–Monocyte Collaborative Induction of Thromboinflammation during Acute Coronary Syndrome

Reduced Contraction of Blood Clots in Venous Thromboembolism Is a Potential Thrombogenic and Embologenic Mechanism

Tumor microenvironment and clonal monocytes from chronic myelomonocytic leukemia induce a procoagulant climate

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