Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: Murine Ortholog of the Fletcher Trait
| Autor: | P. L. Smith, J.-P. Revelli, William A. Schumacher, F. Barbera, J. E. Bird, Xinkang Wang, Dietmar A. Seiffert |
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| Rok vydání: | 2012 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.diagnostic_test Prekallikrein Hematology Kallikrein 030204 cardiovascular system & hematology Biology medicine.disease Plasma Kallikrein Deficiency 03 medical and health sciences Venous thrombosis 030104 developmental biology 0302 clinical medicine Endocrinology Coagulation Bleeding time Internal medicine Immunology medicine Thrombus circulatory and respiratory physiology Partial thromboplastin time |
| Zdroj: | Thrombosis and Haemostasis. 107:1141-1150 |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | SummaryPlasma kallikrein is a multifunctional serine protease involved in contact activation of coagulation. Deficiency in humans is characterised by prolonged activated partial thromboplastin time (aPTT); however, the balance between thrombosis and haemostasis is not fully understood. A study of plasma kallikrein-deficient mice revealed increased aPTT, without prolonged bleeding time. Prekallikrein antisense oligonucleotide (ASO) treatment in mice suggested potential for a positive therapeutic index. The current goal was to further define the role of plasma kallikrein in coagulation. Blood pressure and heart rate were normal in plasma kallikrein-deficient mice, and mice were completely protected from occlusion (100 ± 1.3% control flow) in 3.5% FeCl3 -induced arterial thrombosis versus heterozygotes (20 ± 11.4%) and wild-type littermates (8 ± 0%). Vessels occluded in 8/8 wild-type, 7/8 heterozygotes, and 0/8 knockouts. Anti-thrombotic protection was less pronounced in 5% FeCl3-induced arterial injury. Integrated blood flow was 8 ± 0% control in wild-type and heterozygotes, and significantly (p |
| Databáze: | OpenAIRE |
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