Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: Murine Ortholog of the Fletcher Trait
Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: Murine Ortholog of the Fletcher Trait
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DOI：
10.1160/th11-10-0682
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发表时间：
2012-06-01
影响因子：
6.7
通讯作者：
Seiffert, Dietmar
中科院分区：
文献类型：
--
作者：
Bird, J. Eileen;Smith, Patricia L.;Seiffert, Dietmar
血浆钾化酶是一种参与凝血接触活化的多功能丝氨酸蛋白酶。在人类缺乏的特点是延长活化部分凝血活素时间（aPTT）；然而，血栓和止血之间的平衡尚不完全清楚。一项血浆钾化钾素缺乏小鼠的研究显示aPTT增加，但出血时间没有延长。预钾likrein反义寡核苷酸（ASO）对小鼠的治疗显示出阳性的治疗指标。目前的目标是进一步确定血浆钾化酶在凝血中的作用。血浆钾likrein缺陷小鼠血压和心率正常，与杂合子（20 +/- 11.4%）和野生型（8 +/- 0%）相比，3.5% FeCl3诱导的动脉血栓形成小鼠完全免受闭塞（100 +/- 1.3%控制流量）的保护。8/8野生型、7/8杂合子和0/8敲除型小鼠血管闭塞。在5% fecl3诱导的动脉损伤中，抗血栓保护作用不明显。野生型和杂合子的综合血流量为8 +/- 0%，显著高于对照组(p
Plasma 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