Severe elastolysis in hereditary gelsolin (AGel) amyloidosis
| Autor: | Marc Baumann, Fang Zhao, Sari Kiuru-Enari, Susanna Koskelainen, Hannu Kalimo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Amyloid Pathology medicine.medical_specialty 030204 cardiovascular system & hematology Fibril Cutis Laxa Renal amyloidosis 03 medical and health sciences 0302 clinical medicine Internal Medicine medicine Humans Hereditary gelsolin amyloidosis Gelsolin Aged Aged 80 and over biology Chemistry Amyloidosis Middle Aged medicine.disease Mutation biology.protein Female Amyloidosis Familial Elastin 030217 neurology & neurosurgery Cutis laxa |
| Zdroj: | Amyloid. 27:81-88 |
| ISSN: | 1744-2818 1350-6129 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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