Abstract
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.
Highlights
Abdominal aortic aneurysm (AAA) is a pathological condition characterized by permanent dilation of the abdominal aorta, affecting 4–7% of men over the age of 55 years[1]
We investigated the potential effect of von Willebrand factor (VWF) on AAA pathophysiology using an angiotensin II (AngII)-induced mouse model of AAA development
AAA formation was observed in both Vwf+/+ and Vwf−/− mice and no differences were observed in survival, AAA incidence, severity and several histological parameters
Summary
Abdominal aortic aneurysm (AAA) is a pathological condition characterized by permanent dilation of the abdominal aorta, affecting 4–7% of men over the age of 55 years[1]. VWF is implicated in the regulation of several processes, including thrombosis, hemostasis, vascular stability and inflammation, which together could influence AAA development[4]. Elevated VWF levels have been reported in patients with aortic aneurysms[5] and in patients with ruptured AAAs6. Besides the well characterized thrombo-inflammatory function[8,9], increasing evidence suggests a role of VWF in several vascular processes. Von Willebrand disease, an inherited bleeding disorder caused by quantitative or qualitative defects in VWF, has been associated with different vascular abnormalities, including arterial dissection[10], arterial pseudoaneurysms[11,12,13], gastro-intestinal angiodysplasia[14], arteriovenous malformations[15], and telangiectasia[16]. Whether the different functions of VWF are involved in AAA pathophysiology is currently not known and experimental in vivo studies addressing this question are lacking. A dissection-based AAA model induced by angiotensin II was chosen, as this model is characterized by leukocyte infiltration, elastin degradation and thrombus formation[20]
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