Sampram Ellis S, Saad Yasser, Ouriel Kenneth
Department of Vascular Surgery, The Cleveland Clinic, Cleveland, OH, USA.
Vascular. 2008 Jan-Feb;16(1):31-4. doi: 10.2310/6670.2008.00007.
The factor V Leiden (FVL) mutation has been demonstrated to be associated with the development of venous thrombosis in humans. Whether such a propensity also exists in the arterial circulation remains controversial. In an effort to minimize the variability that clouds the clinical study of arterial thrombosis, we studied FVL-associated arterial thrombosis in an experimental model of homozygous, heterozygous, and wild-type mice. Heterozygous FVL mice were crossbred to C57BL/6J mice over several generations. The genotypes of the resulting three genotype groups (wild type, heterozygous FVL, and homozygous FVL) were blinded to the investigators. Arterial injury was produced with the injection of ferric chloride into an isolated segment of carotid artery. Arterial thrombosis was assessed with an ultrasonic flow probe and the time to occlusion (TTO) was recorded. The carotid artery occluded within 60 minutes of injury in 72 of the animals studied (97.3%). The carotid artery remained patent at 60 minutes in the remaining two animals, both of whom were subsequently found to be genotypically wild type. There was a statistically significant relationship between TTO and genotype (p = .002). TTO was greatest in the wild-type mice (p < .001 vs heterozygous, < .001 vs homozygous) and least in the homozygotes (p < .001 vs heterozygotes). Increased thrombogenicity is present in mice with the FVL mutation and is more prolonged in homozygotes than heterozygotes. These findings provide some corroboration to the clinical studies that suggest an increased risk of arterial events in patients with the FVL mutation.
已证实因子V莱顿（FVL）突变与人类静脉血栓形成有关。这种倾向在动脉循环中是否也存在仍存在争议。为了尽量减少使动脉血栓形成临床研究结果模糊不清的变异性，我们在纯合子、杂合子和野生型小鼠的实验模型中研究了FVL相关的动脉血栓形成。杂合子FVL小鼠与C57BL/6J小鼠杂交了几代。研究人员对所得三个基因型组（野生型、杂合子FVL和纯合子FVL）的基因型不知情。通过向颈动脉的一个孤立节段注射氯化铁来造成动脉损伤。用超声血流探头评估动脉血栓形成，并记录闭塞时间（TTO）。在研究的72只动物中（97.3%），颈动脉在损伤后60分钟内闭塞。其余两只动物的颈动脉在60分钟时仍保持通畅，后来发现它们的基因型均为野生型。TTO与基因型之间存在统计学上的显著关系（p = 0.002）。野生型小鼠的TTO最长（与杂合子相比p < 0.001，与纯合子相比p < 0.001），纯合子的TTO最短（与杂合子相比p < 0.001）。FVL突变小鼠存在血栓形成增加的情况，且纯合子比杂合子更为持久。这些发现为临床研究提供了一些佐证，这些临床研究表明FVL突变患者发生动脉事件的风险增加。
