AGel amyloidosis is a dominantly inherited systemic amyloidosis caused by mutations p.D214N or p.D214Y resulting in gelsolin amyloid (AGel) formation. AGel accumulates extracellularly in many tissues and alongside elastic fibres. AGel deposition associates with elastic fibre degradation leading to severe clinical manifestations, such as cutis laxa and angiopathic complications. We analysed elastic fibre pathology in dermal and vascular tissue and plasma samples from 35 patients with AGel amyloidosis and 40 control subjects by transmission electron microscopy, immunohistochemistry and ELISA methods. To clarify the pathomechanism(s) of AGel-related elastolysis, we studied the roles of MMP-2, -7, -9, -12 and -14, TIMP-1 and TGFβ. We found massive accumulation of amyloid fibrils along elastic fibres as well as fragmentation and loss of elastic fibres in all dermal and vascular samples of AGel patients. Fibrils of distinct types formed fibrous matrix. The degradation pattern of elastic fibres in AGel patients was different from the age-related degradation in controls. The elastin of elastic fibres in AGel patients was strongly decreased compared to controls. MMP-9 was expressed at lower and TGFβ at higher levels in AGel patients than in controls. The accumulation of amyloid fibrils with severe elastolysis characterises both dermal and vascular derangement in AGel amyloidosis.

AGel淀粉样变性是由p.D214N或p.D214Y突变导致凝溶胶蛋白淀粉样蛋白（AGel）形成而引起的遗传性全身性淀粉样变性。AGel在许多组织中以及弹性纤维旁在细胞外积聚。AGel沉积与弹性纤维降解相关，导致严重的临床表现，例如角质层松弛和血管病变。我们通过透射电子显微镜，免疫组织化学和ELISA方法分析了35例AGel淀粉样变性患者和40例对照受试者的皮肤和血管组织及血浆样品中的弹性纤维病理学。为了阐明与AGel相关的弹性溶解的致病机理，我们研究了MMP-2，-7，-9，-12和-14，TIMP-1和TGFβ的作用。我们发现在AGel患者的所有皮肤和血管样本中，淀粉样蛋白原纤维沿着弹性纤维大量堆积，以及弹性纤维的断裂和丢失。不同类型的原纤维形成纤维基质。AGel患者中弹性纤维的降解模式与对照组中与年龄相关的降解不同。与对照组相比，AGel患者的弹性纤维弹性降低。与对照组相比，AGel患者中MMP-9的表达水平较低，而TGFβ的表达水平较高。严重弹性溶解的淀粉样蛋白原纤维的积累是AGel淀粉样变性病中皮肤和血管紊乱的特征。AGel患者中弹性纤维的降解模式与对照组中与年龄相关的降解不同。与对照组相比，AGel患者的弹性纤维弹性降低。与对照组相比，AGel患者中MMP-9的表达水平较低，而TGFβ的表达水平较高。严重弹性溶解的淀粉样蛋白原纤维的积累是AGel淀粉样变性病中皮肤和血管紊乱的特征。AGel患者中弹性纤维的降解模式与对照组中与年龄相关的降解不同。与对照组相比，AGel患者的弹性纤维弹性降低。与对照组相比，AGel患者中MMP-9的表达水平较低，而TGFβ的表达水平较高。严重弹性溶解的淀粉样蛋白原纤维的积累是AGel淀粉样变性病中皮肤和血管紊乱的特征。