Nephrol Dial Transplant (2002) 17: 1450-1456
© 2002 European Renal Association-European Dialysis and Transplant Association
Vascular involvement and cell damage in experimental AA and clinical ß2-microglobulin amyloidosis
1 Institut de Génétique Humaine, CNRS UPR1142, Montpellier, France, 2 Unit of Cell Biology, Department of Biochemistry and Physiology, Faculty of Biology, University of Barcelona, Barcelona, Spain and 3 Department of Nephrology, University Hospital Lapeyronie, Montpellier, France
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 ß2-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-ß2-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 ß2-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.
Keywords: amyloid fibril toxicity; amyloidosis; endothelial cells; experimental amyloidosis; ß2-microglobulin
Correspondence and offprint requests to: Àngel Argilés, Institut de Génétique Humaine, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. Email: angel.argiles{at}igh.cnrs.fr
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