| First Author | Xu F | Year | 2017 |
| Journal | Thromb Res | Volume | 155 |
| Pages | 58-64 | PubMed ID | 28499154 |
| Mgi Jnum | J:241632 | Mgi Id | MGI:5903306 |
| Doi | 10.1016/j.thromres.2017.05.003 | Citation | Xu F, et al. (2017) Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid beta-protein precursor abolishes its anti-thrombotic properties in vivo. Thromb Res 155:58-64 |
| abstractText | INTRODUCTION: Kunitz proteinase inhibitor (KPI) domain-containing forms of the amyloid beta-protein precursor (AbetaPP) inhibit cerebral thrombosis. KPI domain-lacking forms of AbetaPP are abundant in brain. Regions of AbetaPP other than the KPI domain may also be involved with regulating cerebral thrombosis. To determine the contribution of the KPI domain to the overall function of AbetaPP in regulating cerebral thrombosis we generated a reactive center mutant that was devoid of anti-thrombotic activity and studied its anti-thrombotic function in vitro and in vivo. METHODS: To determine the extent of KPI function of AbetaPP in regulating cerebral thrombosis we generated a recombinant reactive center KPIR13I mutant devoid of anti-thrombotic activity. The anti-proteolytic and anti-coagulant properties of wild-type and R13I mutant KPI were investigated in vitro. Cerebral thrombosis of wild-type, AbetaPP knock out and AbetaPP/KPIR13I mutant mice was evaluated in experimental models of carotid artery thrombosis and intracerebral hemorrhage. RESULTS: Recombinant mutant KPIR13I domain was ineffective in the inhibition of pro-thrombotic proteinases and did not inhibit the clotting of plasma in vitro. AbetaPP/KPIR13I mutant mice were similarly deficient as AbetaPP knock out mice in regulating cerebral thrombosis in experimental models of carotid artery thrombosis and intracerebral hemorrhage. CONCLUSIONS: We demonstrate that the anti-thrombotic function of AbetaPP primarily resides in the KPI activity of the protein. |
