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Thrombin Receptors An Important Target In Thrombosis Treatment

  September, 10 2001 21:45
your information resource in human molecular genetics

The protein thrombin is necessary for normal blood clotting, and receptors activated by it may be an important target in the treatment of thrombosis. So conclude Shaun R. Coughlin and colleagues at the University of California, San Francisco, in this week’s Nature (Vol. 413, No. 6851, 06 Sep 2001).

They find that mice lacking molecules that mediate cellular responses to thrombin bleed for longer and seem to be protected from thrombosis. Thrombin cleaves another protein, fibrinogen, in blood plasma, creating single units of fibrin that polymerize into wound-straddling mesh in the vessel wall. Thrombin also activates platelets. Working together, fibrin and platelets create a plug that prevents bleeding long enough for healing to occur. The downside is that clots can also form in blood vessels scarred by cholesterol-laden plaques (atherosclerosis), interrupting blood flow and leading to strokes and heart attacks.

Coughlin’s team investigated one of the key unanswered questions about clotting: the involvement of a protein known as protease-activated receptor-4 (PAR4) in mice. Their results confirm that this receptor is needed for thrombin to activate platelets and for normal clotting in the mouse.

"The implications go beyond this, touching on the fine tuning of platelet activation and intriguing differences between mice and humans," says Skip Brass of University of Pennsylvania, Philadelphia, in an accompanying News and Views article. Brass adds that there may also be implications for developing drugs to prevent cardiovascular problems and strokes.


Shaun R. Coughlin
tel +1 415 476 6174
e-mail coughlin@cvrimail.ucsf.edu

Skip Brass
tel +1 215 573 3540
e-mail brass@mail.med.upenn.edu

(C) Nature press release.

Message posted by: Trevor M. D'Souza

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