title: Gelsolin amyloid angiopathy causes severe disruption of the arterial wall.
abstract: Hereditary gelsolin amyloidosis (HGA) is a dominantly inherited systemic disease reported worldwide. HGA is characterized by ophthalmological, neurological, and dermatological manifestations. AGel amyloid accumulates at basal lamina of epithelial and muscle cells, thus amyloid angiopathy is encountered in nearly every organ. HGA patients have cardiovascular, hemorrhagic, and potentially vascularly induced neurological problems. To clarify pathomechanisms of AGel angiopathy, we performed histological, immunohistochemical, and electron microscopic analyses on facial temporal artery branches from 8 HGA patients and 13 control subjects. We demonstrate major pathological changes in arteries: disruption of the tunica media, disorganization of vascular smooth muscle cells, and accumulation of AGel fibrils in arterial walls, where they associate with the lamina elastica interna, which becomes fragmented and diminished. We also provide evidence of abnormal accumulation and localization of collagen types I and III and an increase of collagen type I degradation product in the tunica media. Vascular smooth muscle cells appear to be morphologically and semi-quantitatively normal, only their basal lamina is often thickened. In conclusion, angiopathy in HGA results in severe disruption of arterial walls, characterized by prominent AGel deposition, collagen derangement and severe elastolysis, and it may be responsible for several, particularly hemorrhagic, disease manifestations in HGA.
authors.affiliation: Meilahti Clinical Proteomics Core Facility, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Koskelainen
authors.affiliation: Department of Plastic Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Tiia
authors.initials: T
authors.lastname: Pihlamaa
authors.affiliation: Department of Plastic Surgery, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Sinikka
authors.initials: S
authors.lastname: Suominen
authors.affiliation: Advanced Microscopy Unit, Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Research Group of Cancer and Translational Medicine, Medical Faculty, University of Oulu, Oulu, Finland.|Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.affiliation: Research Group of Cancer and Translational Medicine, Medical Faculty, University of Oulu, Oulu, Finland.|Medical Research Center, Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
authors.affiliation: Meilahti Clinical Proteomics Core Facility, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Marc
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.|Department of Forensic Medicine, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kalimo
authors.affiliation: Clinical Neurosciences, Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Kiuru-Enari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000682:Amyloid / Q000032:analysis*; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D024042:Collagen Type I / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D013699:Temporal Arteries / Q000473:pathology*; D055815:Young Adult
chemical_list: D000682:Amyloid; D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; C103598:amyloid AGel protein, human
keywords: AGel amyloid angiopathy; Hereditary gelsolin amyloidosis; arterial wall structure; collagen; elastic fibers