Abstract Number: OC 52.2
Meeting: ISTH 2021 Congress
Background: Platelets adhere, become activated and aggregate at site of vessel injury to form a haemostatic plug which stops bleeding. They play an instrumental role in arterial thrombosis in a diseased artery, resulting in life threatening ischaemic pathologies. The role of integrins in regulating platelet function has been extensively studied. Their pathophysiological importance has been investigated with the exception of integrin α5β1, a platelet receptor for fibronectin.
Aims: To characterize the role of α5β1 integrin in platelet responses to fibronectin and to determine its importance in haemostasis and arterial thrombosis in mice.
Methods: We generated a mouse strain which does not express α5β1 on platelets using the PF4Cre/lox recombination system. In vitro flow based-assay was used to monitor platelet adhesion and thrombus formation. Ferric chloride-, pinching- and laser-injury models were used for arterial thrombosis evaluation. The tail-bleeding time assay was used to evaluate haemostasis and reverse passive Arthus reaction for the arrest of inflammatory bleeding.
Results: No obvious abnormalities were detected in PF4Cre-α5-/- mice. Expression of the main platelet surface receptors (αIIbβ3, α2, α6, β1, GPIbα, GPV, GPIX, GPVI) was normal, except for α5 which was markedly reduced. Aggregation of PF4Cre-α5-/- platelets, as well as P-selectin exposure, fibrinogen and annexin V binding were unimpaired in response to a series of soluble agonists including ADP, thrombin and U46619. PF4Cre-α5-/- platelet adhesion under flow was normal on fibrinogen, laminin or von Willebrand factor, but displayed a marked decrease in adhesion, activation and aggregation on fibrillar fibronectin and collagen. No defects were observed in three experimental models of arterial thrombosis. PF4Cre-α5-/- mice presented no increase in tail-bleeding time or cutaneous inflammatory bleeding.
Conclusions: This study shows that platelet α5β1 integrin is an important receptor for fibrillar fibronectin but is dispensable in haemostasis and arterial thrombosis.
To cite this abstract in AMA style:Janus-Bell E, Yakusheva A, Receveur N, Ahmed UM, Mouriaux C, Bourdon C, Panteleev MA, Gachet C, Mangin PH. Characterization of the Role of Integrin α5β1 in Platelet Function, Haemostasis and Arterial Thrombosis in Mice [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/characterization-of-the-role-of-integrin-%ce%b15%ce%b21-in-platelet-function-haemostasis-and-arterial-thrombosis-in-mice/. Accessed December 7, 2021.
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