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Free keywords:
GLYCOPROTEIN-VI; IN-VIVO; ALPHA-GRANULE; COLLAGEN; ALPHA(2)BETA(1);
ACTIVATION; ADHESION; RECEPTOR; KINASE; AGGREGATION
Abstract:
Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific aIIbb3 integrin is known to be crucial for these processes, the in vivo role of beta 1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of beta 1 integrins or an activationdeficient beta 1 integrin show strongly reduced platelet adhesion to collagen in vitro and in a carotis ligation model in vivo. Interestingly, hypomorphic mice expressing only 3% of beta 1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of beta 1 integrins are able to trigger intracellular signals driving Rac-12 dependent granule release required for platelet aggregation and hemostasis. Our findings support a model, in which platelet beta 1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote beta 1 integrins as a promising and so far clinically unemployed antithrombotic target.
