Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
Sci Rep. 2018 Nov 9;8(1):16645. doi: 10.1038/s41598-018-35029-8.
Abdominal aortic aneurysm (AAA) refers to a localized dilation of the abdominal aorta that exceeds the normal diameter by 50%. AAA pathophysiology is characterized by progressive inflammation, vessel wall destabilization and thrombus formation. Our aim was to investigate the potential involvement of von Willebrand factor (VWF), a thrombo-inflammatory plasma protein, in AAA pathophysiology using a dissection-based and angiotensin II infusion-induced AAA mouse model. AAA formation was induced in both wild-type and VWF-deficient mice by subcutaneous implantation of an osmotic pump, continuously releasing 1000 ng/kg/min angiotensin II. Survival was monitored, but no significant difference was observed between both groups. After 28 days, the suprarenal aortic segment of the surviving mice was harvested. Both AAA incidence and severity were similar in wild-type and VWF-deficient mice, indicating that AAA formation was not significantly influenced by the absence of VWF. Although VWF plasma levels increased after the infusion period, these increases were not correlated with AAA progression. Also detailed histological analyses of important AAA hallmarks, including elastic degradation, intramural thrombus formation and leukocyte infiltration, did not reveal differences between both groups. These data suggest that, at least in the angiotensin II infusion-induced AAA mouse model, the role of VWF in AAA pathophysiology is limited.
腹主动脉瘤(AAA)是指腹主动脉局部扩张,超过正常直径的 50%。AAA 的病理生理学特征为进行性炎症、血管壁失稳和血栓形成。我们的目的是使用基于夹层和血管紧张素 II 输注诱导的 AAA 小鼠模型,研究血栓炎症性血浆蛋白 von Willebrand 因子(VWF)在 AAA 病理生理学中的潜在作用。通过皮下植入持续释放 1000ng/kg/min 血管紧张素 II 的渗透泵,在野生型和 VWF 缺陷型小鼠中诱导 AAA 形成。监测生存情况,但两组之间没有观察到显著差异。28 天后,收获存活小鼠的肾上主动脉段。野生型和 VWF 缺陷型小鼠的 AAA 发生率和严重程度相似,表明 VWF 的缺失对 AAA 形成没有显著影响。尽管输注期间 VWF 血浆水平升高,但这些升高与 AAA 进展无关。此外,对 AAA 的重要标志,包括弹性降解、壁内血栓形成和白细胞浸润的详细组织学分析,也没有显示两组之间的差异。这些数据表明,至少在血管紧张素 II 输注诱导的 AAA 小鼠模型中,VWF 在 AAA 病理生理学中的作用是有限的。