REVIEWS  7th INTERNATIONAL CONFERENCE ON TRANSGLUTAMINASES AND PROTEIN CROSSLINKING REACTIONS
Ferrara (Italy), September 14-17, 2002 

Minerva Biotecnologica 2002 June;14(2):121-8

Copyright © 2003 EDIZIONI MINERVA MEDICA

language: English

Factor XIII: state of the art

Ichinose A.

Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan

Fac­tor ­XIII is a zymo­gen­ic trans­glu­tam­i­nase ­whose expres­sion is spe­cif­i­cal­ly restrict­ed to ­some hae­mat­o­poiet­ic ­cells and to pla­cen­ta. In ­these ­cells it is ­present as a dim­er of inac­tive A sub­units. The pro­tein is ­also ­present in plas­ma as a com­plex ­with two B sub­units, syn­the­tized and secret­ed by the liv­er. The con­ver­sion ­into the ­active cross­link­ing ­enzyme is ­obtained by lim­it­ed pro­te­ol­y­sis and interaction with calcium ions. ­Once pro­duced, Fac­tor ­XIIIa cross­links ­fibrin aggre­gates sta­bi­liz­ing them ­against mechan­i­cal ­stress and pro­te­o­lyt­ic deg­ra­da­tion, incor­po­rat­ing pro­tei­nase inhib­i­tors ­into the ­fibrin ­clot. Genet­ic defi­cien­cies of Fac­tor ­XIII, result­ing in haem­or­rhag­ic dis­eas­es, are now ­known and ­their path­o­gen­e­sis is dis­cussed at the ­light of ­recent molec­u­lar biol­o­gy and in vivo inac­ti­va­tion (­knock-out) experi­ments. I ­also ­detail on the recent­ly dem­on­strat­ed asso­ci­a­tion ­between spe­cif­ic Fac­tor ­XIII poly­mor­phic ­forms and ­risk of car­di­o­vas­cu­lar dis­eas­es (myo­car­dial infarc­tion and ­venous throm­bo­sis).