Aortic aneurysm refers to dilatation of the aorta due to loss of elasticity and degenerative weakening of its wall. A preventive role for osteoprotegerin (Opg) in the development of abdominal aortic aneurysm has been reported in the CaCl₂-induced aneurysm model, whereas Opg was found to promote suprarenal aortic aneurysm in the AngII-induced ApoE knockout mouse aneurysm model. To determine whether there is a common underlying mechanism to explain the impact of Opg deficiency on the vascular structure of the two aneurysm models, we analyzed suprarenal aortic tissue of 6-month-old ApoE^-/-Opg^-/- mice after AngII infusion for 28 days. Less aortic dissection and aortic lumen dilatation, more adventitial thickening, and higher expression of collagen I and Trail were observed in ApoE^-/-Opg^-/- mice relative to ApoE^-/-Opg^+/+ mice. An accumulation of α-smooth muscle actin and vimentin double-positive myofibroblasts was noted in the thickened adventitia of ApoE^-/-Opg^-/- mice. Our results suggest that fibrotic remodeling of the aorta induced by myofibroblast accumulation might be an important pathological event which tends to limit AngII-induced aortic dilatation in ApoE ^-/-Opg^-/- mice.

主动脉瘤是指由于弹性丧失和其壁的退化性减弱而引起的主动脉扩张。在CaCl ₂诱导的动脉瘤模型中已经报道了骨保护素（Opg）在腹主动脉瘤形成中的预防作用，而在AngII诱导的ApoE敲除小鼠动脉瘤模型中发现Opg可以促进肾上动脉主动脉瘤。为了确定是否存在共同的潜在机制来解释Opg缺乏对两种动脉瘤模型的血管结构的影响，我们分析了6个月大的ApoE ^-/- Opg ^-/-的肾上主动脉组织AngII输注28天后的小鼠。相对于ApoE ^-/- Opg ^{+ / +}小鼠，在ApoE ^-/- Opg ^-/-小鼠中观察到较少的主动脉夹层和主动脉腔扩张，更多的外膜增厚以及较高的I和Trail胶原蛋白表达。在ApoE ^-/- Opg ^-/-小鼠的外膜增厚中，注意到了α平滑肌肌动蛋白和波形蛋白双阳性肌成纤维细胞的积累。我们的结果表明由成肌纤维细胞积累引起的主动脉纤维化重塑可能是重要的病理事件，它倾向于限制AngII诱导的ApoE ^-/- Opg ^-/-的主动脉扩张。 老鼠。