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.

Atypical Presentation of Gelsolin Amyloidosis in a Man of African Descent with a Novel Mutation in the Gelsolin Gene

“…In our case, there was proven mucosal gingival involvement by amyloid (data not shown) and suspected involvement of the liver, heart, and kidney, which suggests an already existing and widespread amyloidogenic protein deposition. In further support of the widespread amyloidogenic protein deposition, the previously described blood vessel changes found in gelsolin amyloid angiopathy were also identified in our patient [ 19 ]. The major pathological changes in the arteries are shown in Figure 2A (H&E stain) thickened vascular wall with accumulation of abundant nodular AGel fibrils, which disrupt the tunica media with disorganization and replacement of vascular smooth muscle cells.…”

Recurrent profuse hemorrhage after chalazion excision in a patient with systemic amyloidosis

“…4 Second, it can locally increase bleeding by causing amyloid angiopathy where the amyloid infiltrates the vessel walls, decreasing the stability of the vascular architectureand resulting in fragile blood vessels with impaired ability to vasoconstrict. [4][5][6] It is well known that primary amyloidosis of the lids and conjunctiva is characterized by hemorrhagic lesions. Although this patient had no preoperative signs of conjunctival amyloidosis, her history should have suggested an increased risk for hemorrhage.…”

Clinical considerations in early-onset cerebral amyloid angiopathy

“… 172 , 180 Other features can include myokymia, autonomic dysfunction, gait ataxia and the consequences of cardiac and renal involvement. 172 , 180 Pathologically, there is deposition of AGel throughout in multiple organs and particularly involving the basement membranes of epithelial, smooth and striated muscle cells 177 , 181 ; in the CNS deposition is predominantly vascular, and involves the grey and white matter of the brain, 182 , 183 spinal cord and meninges. 182 …”