The Concept of Thromboinflammation

Schrottmaier, Waltraud C.; Assinger, Alice

doi:10.1055/a-2178-6491

Cited by 2 publications

(1 citation statement)

References 84 publications

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“…Yet, notably high thrombusblood ratios of monocytes and neutrophils (vs. those of lymphocytes) suggest these leukocytes were actively recruited. Gene expression analysis also showed upregulation of cytokines (CCL2, CCL5, CCL7, CXCL2, CX3CR1, IL-6, and IL-1b), which may have facilitated leukocyte recruitment into thrombus [28][29][30] in the lesional (vs. non-thrombosed contralateral) carotid arteries. Thus, less monocyte recruitment to arterial thrombi as well as lower monocyte counts in the blood may have decreased monocyte-platelet interaction and platelet aggregability during acute arterial thrombosis in CCR2 -/mice, compared to C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 96%

Inhibiting monocyte migration reduces arterial thrombosis and facilitates thrombolysis

Jang,

Kim,

Kim

et al. 2024

Preprint

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Background: Monocytes contribute to the initiation and propagation of venous thrombosis. Little is known about the roles monocytes play in arterial thrombosis, the cause of stroke and MI. Methods: We investigated how chemokine receptor 2 (CCR2) knockout (&ndash/&ndash) affects platelet function, blood coagulation, thrombus volume, and thrombolytic susceptibility in 627 mice with FeCl3–mediated carotid arterial thrombosis: three CX3CR1–GFP mice, 326 C57BL/6 mice, and 288 CCR2&ndash/&ndashmice. We performed i) intravital microscopy imaging of leukocyte recruitment to carotid thrombus, ii) flow cytometry&ndashbased quantification of leukocytes in blood vs. thrombus and leukocyte-platelet aggregates in blood, iii) platelet aggregometry, iv) coagulation assays, v) micro&ndashcomputed tomography (microCT)&ndashbased thrombus imaging using gold nanoparticles after tissue plasminogen activator (tPA) therapy with or without either a) CCR2 siRNA pretreatment (for 3 days) or post&ndashtreatment or b) clopidogrel pretreatment (for 7 days), and vi) histology including scanning electron microscopy. Results: Intravital microscopy and flow cytometry showed that both neutrophils and monocytes were recruited to the acute arterial thrombus, as observed 30 minutes post&ndashthrombosis. Platelet function tests demonstrated platelet aggregation to be lower in the whole blood of CCR2&ndash/&ndashmice (vs. C57BL/6 mice) but not in their leukocyte&ndashfree platelet rich plasma, suggesting this platelet dysfunction is cell&ndashmediated. Flow cytometry experiments revealed lower numbers of monocyte&ndashplatelet aggregates (MPAs), a marker of platelet activity, in the blood of CCR2&ndash/&ndashmice, compared to C57BL/6 mice. Blood levels of FXIII and monocyte levels of FXIII&ndashA were increased after carotid thrombosis in C57BL/6 mice but not CCR2–/–mice. Further, in vivo microCT and histology, respectively, showed that CCR2&ndash/&ndashmice had smaller and more porous thrombi with less fibrin cross&ndashlinking, compared with C57BL/6 mice. MicroCT also demonstrated that tPA&ndashmediated thrombolysis was faster in CCR2&ndash/&ndashmice and CCR2 siRNA&ndashtreated mice, compared to C57BL/6 mice. In addition, clopidogrel had a greater effect on inducing thrombus formation with smaller sizes after FeCl3application, while CCR2&ndash/&ndashhad a greater effect on dissolving thrombus faster after tPA administration. Conclusions: CCR2 antagonism decreases platelet aggregation and reduces FXIII levels in blood and monocytes, thus driving arterial thrombosis towards the generation of a relatively small, porous, more lysable clot.

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Section: Discussionmentioning

confidence: 96%

Inhibiting monocyte migration reduces arterial thrombosis and facilitates thrombolysis

Jang,

Kim,

Kim

et al. 2024

Preprint

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Hemostasis and complement in allogeneic hematopoietic stem cell transplantation: clinical significance of two interactive systems

Tsakiris,

Gavriilaki,

Chanou

et al. 2024

Bone Marrow Transplant

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Hematopoietic stem cell transplantation (HCT) represents a curative treatment option for certain malignant and nonmalignant hematological diseases. Conditioning regimens before HCT, the development of graft-versus-host disease (GVHD) in the allogeneic setting, and delayed immune reconstitution contribute to early and late complications by inducing tissue damage or humoral alterations. Hemostasis and/or the complement system are biological regulatory defense systems involving humoral and cellular reactions and are variably involved in these complications after allogeneic HCT. The hemostasis and complement systems have multiple interactions, which have been described both under physiological and pathological conditions. They share common tissue targets, such as the endothelium, which suggests interactions in the pathogenesis of several serious complications in the early or late phase after HCT. Complications in which both systems interfere with each other and thus contribute to disease pathogenesis include transplant-associated thrombotic microangiopathy (HSCT-TMA), sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), and GVHD. Here, we review the current knowledge on changes in hemostasis and complement after allogeneic HCT and how these changes may define clinical impact.

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The Concept of Thromboinflammation

Cited by 2 publications

References 84 publications

Inhibiting monocyte migration reduces arterial thrombosis and facilitates thrombolysis

Inhibiting monocyte migration reduces arterial thrombosis and facilitates thrombolysis

Hemostasis and complement in allogeneic hematopoietic stem cell transplantation: clinical significance of two interactive systems

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