[The contact factors of hemostasis: examination of molecular evolution and new therapeutic perspectives].
Enterprises of whole genome sequencing together with information technology progress enable reconstruction of blood clotting evolution by bioinformatic methods. It together offers a base to conclude that the contact phase of vertebrate blood coagulation is evolutionary young and shaped merely before divergence of marsupial and placental mammals. Amphibians, birds and platypus own a single gene corresponding to the predecessor of factor XI and plasma prekallikrein. The opossum has both PK and FXI like eutherian mammals. FXII appears first in amphibians, it is present in platypus and opossum, but disappears in lineage leading to birds, probably by gene loss. The last findings brought to live the intrinsic coagulation pathway as it was discovered that FXII-knockout mice were protected from experimentally induced thrombosis, with no changes of proper clotting. The contact proteases may be a target for new antithrombotic therapies.
Ponczek
Michał Błazej
MB
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 12/16 Banacha St., 90-237, Lodz, Poland. mponczek@biol.uni.lodz.pl
D000663:Amphibians; D000818:Animals; D001717:Birds; D001777:Blood Coagulation / Q000235:genetics*; D019143:Evolution, Molecular; D005172:Factor XI / Q000235:genetics; D005174:Factor XII / Q000235:genetics; D006801:Humans; D008322:Mammals; D051379:Mice; D009893:Opossums; D010802:Phylogeny; D010987:Platypus; D011288:Prekallikrein / Q000235:genetics; D013045:Species Specificity; D014714:Vertebrates
D005174:Factor XII; D005172:Factor XI; D011288:Prekallikrein