Blood coagulation factor Xa as an emerging drug target.
BACKGROUND
Factor (F)Xa is well-known as an important player in the coagulation cascade responsible for thrombin generation. More recently, FXa emerged as an essential player in cell biology via activation of protease-activated receptors (PAR)-1 and -2. This pleiotropic role of FXa forms the basis for its potential contribution to the pathogenesis of several diseases.


METHODS
The role of FXa in pathophysiology is reviewed with special emphasis on its signal transduction properties. To this end, we first discuss the important role of FXa in the coagulation cascade, we continue with recent data on FXa induced signaling in pathophysiology with special emphasis on tissue remodeling and fibrosis and discuss the potential of FXa as an emerging drug target.


CONCLUSIONS
FXa is more than a passive intermediate in the coagulation cascade and FXa may in fact orchestrate fundamental processes during pathophysiology. Targeting FXa may be an exciting new therapeutic strategy in the treatment of (fibro)proliferative diseases for which current treatment options are limited.
Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, NL-1105 AZ, Amsterdam, The Netherlands.
Keren
K
Borensztajn
C Arnold
CA
Spek
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000502:physiology; D016503:Drug Delivery Systems; D015951:Factor Xa / Q000378:metabolism*; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D044463:Receptor, PAR-1 / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism
D000925:Anticoagulants; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D013917:Thrombin; D015951:Factor Xa