Microparticles, Vascular Function, and Atherothrombosis

Rautou, Pierre‐Emmanuel; Vion, Anne-Clémence; Amabile, Nicolas; Chironi, Gilles; Simon, Alain; Tedgui, Alain; Boulanger, Chantal M.

doi:10.1161/circresaha.110.233163

Cited by 337 publications

(299 citation statements)

References 204 publications

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“…Microparticles (MPs) are 0.1-1-μm membrane vesicles that are released into the extracellular space following cell activation or apoptosis 33) . Several cardiovascular risk factors, such as oxidative stress and elevated levels of lipoproteins and cytokines, increase the release of MPs from vascular/circulation cells 34,35) , and a large number of studies have proposed that MPs may contribute to atherosclerotic plaque development and thrombus formation/progression [35][36][37][38] . In fact, circulating MPs (primarily endothelial and leukocyte MPs), which contribute to the initiation of atherosclerosis due to endothelial dysfunction by decreasing nitric oxide synthesis, have been reported to be significantly higher in ACS patients 39) and are considered to be a primary source of the blood-borne tissue factor involved in thrombus propagation at the site of vascular injury 38,40,41) .…”

Section: Role Of Tissue Factor and Microparticles In Thrombus Formationmentioning

confidence: 99%

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

Yunoki

Naruko

Sugioka

et al. 2013

JAT

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Inflammation and oxidative stress play key roles in atherosclerotic plaque instability, and plaque rupture/erosion and subsequent thrombus formation constitute the principal mechanisms of total vessel occlusion and acute ST-elevation myocardial infarction (STEMI). Plaque disruption triggers the formation of initial platelet aggregates that grow in association with an increase in fibrin formation, leading to persistent coronary flow obstruction and blood coagulation. The fibrin network may trap large numbers of erythrocytes and inflammatory cells to form an erythrocyte-rich thrombus. In fact, previous clinical studies have shown that not only platelet-rich white thrombi, but also erythrocyte-rich red thrombi can be visualized using angioscopy in patients with acute coronary syndrome. Recently, the development of thrombus aspiration and distal protection devices has significantly improved the clinical outcomes of percutaneous intervention in STEMI patients and has enabled the evaluation of antemortem coronary artery thrombi. This is important because previous autopsy studies were unable to differentiate coronary thrombi responsible for myocardial ischemia from postmortem clots. Using frozen samples of aspirated thrombi and specific monoclonal antibodies, we investigated the cellular components of thrombi (platelets, erythrocytes, fibrin and inflammatory cells, such as myeloperoxidase-positive cells) and pathologically evaluated the relationships between erythrocyterich thrombi and inflammation, oxidative stress and clinical outcomes in STEMI patients. Therefore, this review article focuses on the efficacy of thrombus aspiration therapy and the components of aspirated intracoronary thrombi in STEMI patients and presents the results of recent studies regarding the relationship between the composition of aspirated intracoronary thrombi and clinical outcomes.

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Section: Role Of Tissue Factor and Microparticles In Thrombus Formationmentioning

confidence: 99%

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

Yunoki

Naruko

Sugioka

et al. 2013

JAT

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“…20 First, we determine whether thrombin, CD40L, or the combination induced the release of endothelial MPs harboring MMP-10 (MMP-10 1 EMPs), as well as the contribution of MMP-10…”

Section: Endothelial and Platelet Activation Induce Mp Generation Beamentioning

confidence: 99%

Synergistic Effect of Thrombin and CD40 Ligand on Endothelial Matrix Metalloproteinase-10 Expression and Microparticle Generation In Vitro and In Vivo

Lizarrondo

Roncal

Calvayrac

et al. 2012

ATVB

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Objective— Thrombin induces CD40 ligand (CD40L) and matrix metalloproteinases (MMPs) under inflammatory/prothrombotic conditions. Thrombin and CD40L could modulate endothelial MMP-10 expression in vitro and in vivo. Methods and Results— Human endothelial cells were stimulated with thrombin (0.1–10 U/mL), CD40L (0.25–1 μg/mL), or their combination (thrombin/CD40L) to assess MMP-10 expression and microparticle generation. Thrombin/CD40L elicited higher MMP-10 mRNA (5-fold; P <0.001) and protein levels (4.5-fold; P <0.001) than either stimulus alone. This effect was mimicked by a protease-activated receptor-1 agonist and antagonized by hirudin, a-protease-activated receptor-1, α-CD40L, and α-CD40 antibodies. The synergistic effect was dependent on p38 mitogen-activated protein kinase and c-Jun N -terminal kinase-1 pathways. Thrombin also upregulated the expression of CD40 in endothelial cell surface increasing its availability, thereby favoring its synergistic effects with CD40L. In mice, thrombin/CD40L further increased the aortic MMP-10 expression. Septic patients with systemic inflammation and enhanced thrombin generation (n=60) exhibited increased MMP-10 and soluble CD40L levels associated with adverse clinical outcome. Endothelial and systemic activation by thrombin/CD40L and lipopolysaccharide also increased microparticles harboring MMP-10 and CD40L. Conclusion— Thrombin/CD40L elicited a strong synergistic effect on endothelial MMP-10 expression and microparticles containing MMP-10 in vitro and in vivo, which may represent a new link between inflammation/thrombosis with prognostic implications.

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“…These include inorganic polyphosphates (PolyPs) [14], released following cell damage and infection, but also extracellular RNA and DNA, as recently demonstrated [11]. The role of procoagulant MPs has been highly investigated in different disorders [10,15]. PolyPs are anionic linear polymers ATP-derived, mainly secreted following platelets activation [14].…”

Section: Coagulation Cascade: Something New?mentioning

confidence: 99%

The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target?

Cimmino¹,

Fischetti²,

Golino³

2017

J Thrombo Cir

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Acute thrombus formation is the pathophysiological substrate underlying several clinical conditions, such as acute coronary syndrome (ACS) and stroke. Activation of coagulation cascade is a key step of the thrombotic process: vessel injury results in exposure of the glycoprotein tissue factor (TF) to the flowing blood. Once exposed, TF binds factor VII/VIIa (FVII/FVIIa) and in presence of calcium ions, it forms a tertiary complex able to activate FX to FXa, FIX to FIXa, and FVIIa itself. The final step is thrombin formation at the site of vessel injury with subsequent platelet activation, fibrinogen to fibrin conversion and ultimately thrombus formation.Platelets are the key cells in primary hemostasis. For years they have been considered only as cell fragments participating to primary hemostasis and onto which coagulation factors are assembled in the process of thrombus formation. However, recent advances in platelets pathophysiology have shown that these cells are able to regulate their gene and protein expression, make de novo protein synthesis, and release different mediators with paracrine effects that may interfere with different cell functions.Pharmacological modulation of both side of thrombosis, coagulation cascade and platelet activation, is of great clinical importance. Several clinical trials have clearly shown the efficacy of anticoagulation and/or anti platelet aggregation in different thrombotic disorders. This article aims at reviewing the recent advancements on the two faces of thrombosis focusing on the emerging role of platelets not only as clot-forming components, but highlighting their involvement in the inflammatory-immune system, as well as in modulation of different cell functions.

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Microparticles, Vascular Function, and Atherothrombosis

Cited by 337 publications

References 204 publications

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

Synergistic Effect of Thrombin and CD40 Ligand on Endothelial Matrix Metalloproteinase-10 Expression and Microparticle Generation In Vitro and In Vivo

The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target?

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