title: Vascular involvement and cell damage in experimental AA and clinical beta(2)-microglobulin amyloidosis.
abstract: BACKGROUND
  Amyloidosis is a highly prevalent disease characterized by the deposition of amyloid fibrils. Although several types of amyloidosis can be identified according to their protein constituents and suggest putative aetiological factors, the causes of amyloidosis remain unknown. Furthermore, the cellular participation and the ultrastructural particularities of amyloidosis have received little attention. The aim of our study was to evaluate the vascular participation in amyloidosis and the cellular consequences of this disease.
  
  
  METHODS
  Two forms of amyloidosis were studied: experimental amyloid A (AA) and clinical beta(2)-microglobulin amyloidosis. We studied kidney, liver, and spleen in a mouse model, and examined surgically obtained carpal deposits from dialysis patients. We used light and electron microscopy with immunogold labelling for anti-beta(2)-microglobulin and anti-AA protein antibodies.
  
  
  RESULTS
  AA amyloid fibril accumulation was associated with membrane lesions in basal, cytoplasmic organelle (endoplasmic reticulum, mitochondria), and nuclear membranes. Amyloid fibrils from beta(2)-microglobulin amyloidosis were also closely associated with elastic fibres and endothelial basement membrane. We observed proliferation of endothelial cells as well as basement membrane enlargement and disruption.
  
  
  CONCLUSIONS
  Vascular abnormalities, including endothelial enlargement, basement membrane modifications, and vascular proliferation were associated with amyloidosis. Amyloid fibrils have a high avidity for elastic fibres and are able to contact and damage the basement membrane, the cell and intracellular organelle membranes, as well as the nuclear envelope, suggesting a toxic effect of amyloid fibrils on cells.
authors.affiliation: Institut de Génétique Humaine, CNRS UPR1142, Montpellier, France.
authors.forename: Mar
authors.initials: M
authors.lastname: García-García
authors.forename: Georges
authors.initials: G
authors.lastname: Mourad
authors.forename: Mercè
authors.initials: M
authors.lastname: Durfort
authors.forename: José
authors.initials: J
authors.lastname: García-Valero
authors.forename: Angel
authors.initials: A
authors.lastname: Argilés
mesh_terms: D000686:Amyloidosis / Q000150:complications / Q000209:etiology / Q000473:pathology*; D000818:Animals; D001808:Blood Vessels / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D017582:Renal Replacement Therapy / Q000009:adverse effects; D000685:Serum Amyloid A Protein / Q000032:analysis*; D014652:Vascular Diseases / Q000209:etiology / Q000473:pathology*; D001613:beta 2-Microglobulin / Q000032:analysis*
chemical_list: D000685:Serum Amyloid A Protein; D001613:beta 2-Microglobulin