Dataset Information

A thrombus is formed by a gradient of platelet activation and procoagulant endothelium.

ABSTRACT:

Background

The contribution of platelets in thrombosis within microcirculation has been extensively documented in the literature. We previously showed, in vivo, that platelet activation revealed by intracellular calcium mobilization was a crucial step in the growth of thrombi following laser-induced injury, a model of thromboinflammation.

Objective

Our goal was to investigate the extent of platelet activation and the spatial distribution of platelets throughout a growing thrombus.

Methods

We employed a multimodal, correlative microscopy approach and computational biology to study the state of platelets on a growing thrombus obtained after a laser injury.

Results

We observed a reversible intracellular platelet calcium mobilization that correlates with the time a platelet resides during thrombus growth. Our bioinformatics analysis displayed the following 3 distinct platelet subpopulations resident within a thrombus: (1) resting, (2) partially activated, and (3) "fully" activated platelets. The spatial distribution of the platelet subpopulations in the thrombus creates a double gradient in both the transversal and longitudinal axis, with the maximal percentage of fully activated platelets close to the site of injury. However, these activated platelets did not express negative phospholipids. The injured endothelium was identified to play a vital role in activating the blood coagulation cascade in this model of thrombosis.

Conclusion

Following a laser-induced injury, thrombi are formed by a gradient of activated platelets from the injury site to the periphery of the thrombus. These different activation states of platelets throughout the thrombi regulate the biomechanics of the thrombus. The injured endothelium, rather than platelets, was identified to play a key role in the activation of the blood coagulation cascade in this model of thromboinflammation.

SUBMITTER: Carminita E

PROVIDER: S-EPMC10704518 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A thrombus is formed by a gradient of platelet activation and procoagulant endothelium.

Carminita Estelle E Tourn Julie J Crescence Lydie L Brouilly Nicolas N Merrill-Skoloff Glenn G Mazharian Alexandra A Dubois Christophe C Panicot-Dubois Laurence L

Research and practice in thrombosis and haemostasis 20230921 7

<h4>Background</h4>The contribution of platelets in thrombosis within microcirculation has been extensively documented in the literature. We previously showed, <i>in vivo</i>, that platelet activation revealed by intracellular calcium mobilization was a crucial step in the growth of thrombi following laser-induced injury, a model of thromboinflammation.<h4>Objective</h4>Our goal was to investigate the extent of platelet activation and the spatial distribution of platelets throughout a growing th ...[more]

PMID: 38077809

Similar Datasets

Project description:Thrombosis, like other cardiovascular diseases, has a strong genetic component, with largely unknown determinants. EMILIN2, Elastin Microfibril Interface Located Protein2, was identified as a candidate gene for thrombosis in mouse and human quantitative trait loci studies. EMILIN2 is expressed during cardiovascular development, on cardiac stem cells, and in heart tissue in animal models of heart disease. In humans, the EMILIN2 gene is located on the short arm of Chromosome 18, and patients with partial and complete deletion of this chromosome region have cardiac malformations. To understand the basis for the thrombotic risk associated with EMILIN2, EMILIN2 deficient mice were generated. The findings of this study indicate that EMILIN2 influences platelet aggregation induced by adenosine diphosphate, collagen, and thrombin with both EMILIN2-deficient platelets and EMILIN2-deficient plasma contributing to the impaired aggregation response. Purified EMILIN2 added to platelets accelerated platelet aggregation and reduced clotting time when added to EMILIN2-deficient mouse and human plasma. Carotid occlusion time was 2-fold longer in mice with platelet-specific EMILIN2 deficiency, but stability of the clot was reduced in mice with both global EMILIN2 deficiency and with platelet-specific EMILIN2 deficiency. In vitro clot retraction was markedly decreased in EMILIN2 deficient mice, indicating that platelet outside-in signaling was dependent on EMILIN2. EMILIN1 deficient mice and EMILIN2:EMILIN1 double deficient mice had suppressed platelet aggregation and delayed clot retraction similar to EMILIN2 mice, but EMILIN2 and EMILIN1 had opposing affects on clot retraction, suggesting that EMILIN1 may attenuate the effects of EMILIN2 on platelet aggregation and thrombosis. In conclusion, these studies identify multiple influences of EMILIN2 in pathophysiology and suggest that its role as a prothrombotic risk factor may arise from its effects on platelet aggregation and platelet mediated clot retraction.

Dataset Information

A thrombus is formed by a gradient of platelet activation and procoagulant endothelium.

Background

Objective

Methods

Results

Conclusion

Publications

A thrombus is formed by a gradient of platelet activation and procoagulant endothelium.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets