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. 2023 Nov:231:159-169.
doi: 10.1016/j.thromres.2022.08.010. Epub 2022 Aug 19.

Molecular basis of clot retraction and its role in wound healing

Alan T Nurden  1
Affiliations

Molecular basis of clot retraction and its role in wound healing

Alan T Nurden. Thromb Res. 2023 Nov.

Abstract

Clot retraction is important for the prevention of bleeding, in the manifestations of thrombosis and for tissue repair. The molecular mechanisms behind clot formation are complex. Platelet involvement begins with adhesion at sites of vessel injury followed by platelet aggregation, thrombin generation and fibrin production. Other blood cells incorporate into a fibrin mesh that is consolidated by FXIIIa-mediated crosslinking and platelet contractile activity. The latter results in the asymmetric redistribution of erythrocytes into a tighter central mass providing the clot with stability and resistance to fibrinolysis. Integrin αIIbβ3 on platelets is the key player in these events, bridging fibrin and the platelet cytoskeleton. Glycoprotein VI participates in thrombus formation but not in the retraction. Rheological and environmental factors influence clot construction with retraction driven by the platelet cytoskeleton with actomyosin acting as the motor. Activated platelets provide procoagulant activity stimulating thrombin generation together with the release of a plethora of biologically active proteins and substances from storage pools; many form chemotactic gradients within the fibrin or the underlying matrix. Also released are newly synthesized metabolites and lipid-rich vesicles that circulate within the vasculature and mimic platelet functions. Platelets and their released elements play key roles in wound healing. This includes promoting stem cell and mesenchymal stromal cell recruitment, fibroblast and endothelial cell migration, angiogenesis and matrix formation. These properties have led to the use of autologous clots in therapies designed to accelerate tissue repair while offering the potential for genetic manipulation in both inherited and acquired diseases.

Keywords: Clot retraction; FXIII; GPVI; actomyosin; fibrin; integrin αIIbβ3; platelets; thrombin; thrombosis; wound healing.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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