ANTIPLASMIN CLEAVING ENZYME

摘要

Human .alpha.2-antiplasmin (.alpha.2AP) is the major inhibitor of the proteolytic enzyme plasmin that digests fibrin. Two forms of .alpha.2AP circulate in human plasma: a 464-residue protein, which we have termed "pro" - form, or .alpha.2APpro,and an N-terminally-shortened 452-residue "activated" - form, or .alpha.2APact. The latter becomes crosslinked to fibrin by activate d factor XIII about 5-fold more rapidly than .alpha.2APpro and makes fibrin resistant to digestion by plasmin. A new human plasma proteinase has been identified herein that cleaves the Pro12-Asn13 bond of .alpha.2APpro to yiel d .alpha.2APact. This enzyme is identified herein as Antiplasmin Cleaving Enzy me (APCE). Novel inhibitors of circulating APCE can diminish .alpha.2AP inhibitory capacity within forming fibrin or blood clots thereby making fibr in deposits or blood clots more susceptible to removal by plasmin. Patients who are susceptible to atherosclerotic plaque formation or are susceptible to developing thrombi that compromise organ function will benefit by therapies providing such inhibitors on a long term basis.