A novel model of occlusive thrombus formation in mice

Abstract

A novel model to induce occlusive thrombus formation was developed in mice in vivo. Mice were simultaneously treated with ligation and cuff placement at the left carotid artery. At 7 days after the treatment, occlusive thrombus was observed at the intracuff region, but not in the distal and proximal regions of the cuff, and not induced by a single treatment of ligation or cuff placement. The plasma levels of von Willebrand factor (vWF), which represent the endothelial status, were significantly increased in combined treatment of ligation and cuff placement 1 day after the operation. Whereas no significant changes in plasma vWF were observed in either single treatment of ligation or cuff placement. The expression of vWF, considered to be the endothelial marker, was detected on the luminal surface distal and proximal to the cuff and the carotid artery in the single treatment groups treated with either ligation or cuff placement, but was not detected in the intracuff region. Furthermore, the binding of Griffolia Simplicifolia Lectin-I (GSL-I) and endothelial nitric oxide synthase (eNOS) expression indicating the endothelial integrity was not detected in the intracuff region. Intermittent injections of ancrod, which decreases the plasma fibrinogen, inhibited occlusive thrombus formation in the intracuff region. The expression of eNOS was detected at the distal and proximal but not the intracuff region of the carotid artery treated with ancrod. Daily administration of aspirin significantly suppressed the thrombus formation in this model. These results indicate that occlusive thrombus formation accompanied by endothelial damage or dysfunction is induced by the combined application of ligation and cuff placement at the carotid artery, and suggest that this endothelial damage or dysfunction may be one pathogenesis of thrombogenesis in this model.

Murine Models of Vascular Thrombosis

“…Methods previously used involve ligation, 32 perivascular electrical injury, 33 and placement of a polyethylene cuff. 34 Ligation models that induce stasis have been particularly useful for studying factors involved in venous thrombosis. 35 A wire injury model in which a 0.25-or 0.35-millimeter angioplasty guide wire is advanced into the femoral ( Figure 1D) or carotid artery, respectively, has been commonly used to induce intimal hyperplasia in mice, which develops over the course of several weeks after injury.…”

A Simple Method of Plaque Rupture Induction in Apolipoprotein E–Deficient Mice

“…11 Four weeks after ligation, a polyethylene cuff (length 2 mm; inside and outside diameter 0.580 mm and 0.965 mm, respectively; Becton Dickinson) was applied just proximal to the ligated site according to the method described previously. 12 In the control group, the dissection of the left common carotid artery from the surrounding connective tissue was performed without cuff placement.…”

Ablation of Angiotensin IV Receptor Attenuates Hypofibrinolysis via PAI-1 Downregulation and Reduces Occlusive Arterial Thrombosis

“…In this study, we evaluated both acute fibrinolysis and chronic thrombosis using 3 different mouse models: the acute disseminated intravascular coagulation (DIC) model induced by endotoxinemia, 20 the ferric chloride (FeCl 3 )-induced thrombosis model, 21,22 and the ligation and cuff placement model in the carotid artery. 23 We aimed to determine whether the genetic ablation of AT4R could attenuate thrombosis and inflammation using IRAP-deficient mice (IRAP Ϫ/Ϫ ). Our data provide an important insight into the novel association between RAS and thrombosis and heightens awareness to a pivotal role of IRAP/AT4R in the pathogenesis of cardiovascular disease.…”