Effect of poly(vinylsulfonate) on murine AA amyloid: a high-resolution ultrastructural study.
In experimental murine inflammation-associated amyloidosis (AA amyloidosis), an interaction between heparan sulfate and serum amyloid A (SAA), the AA precursor, has been demonstrated and is believed to play an important role in AA amyloidogenesis. Poly(vinylsulfonate) sodium salt (PVS) can arrest AA amyloid induction and cause established amyloid deposits to regress. PVS is thought to have this property by virtue of limited anionic structural similarities it has to heparan sulfate. In the present study, a comparison has been made of the in situ light microscopic and high-resolution ultrastructure of amyloid deposits before and after PVS treatment. As shown recently in situ, AA fibrils from untreated mice are composed of an outer layer of heparan sulfate proteoglycan and a 1- to 2-nm filament network of AA protein. This layer encloses a microfibril-like structure composed of chondroitin sulfate proteoglycan wound around a core of amyloid P component. After treatment with PVS, both the heparan sulfate proteoglycan and the AA filament network are lost from the fibrils, and the more central portion disintegrates into the chondroitin sulfate proteoglycan with associated amyloid P subunits. These findings add further support to the concept that heparan sulfate proteoglycan is important in amyloid fibril structure, and interference with its binding interactions with the amyloid filament protein provides a point of therapeutic attack.
Inoue
S
S
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Hultin
P G
PG
Szarek
W A
WA
Kisilevsky
R
R
D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D011145:Polyvinyls / Q000494:pharmacology* / Q000627:therapeutic use; D000685:Serum Amyloid A Protein / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000648:ultrastructure*; D013154:Spleen / Q000737:chemistry / Q000187:drug effects; D013451:Sulfonic Acids / Q000494:pharmacology* / Q000627:therapeutic use
D011145:Polyvinyls; D000685:Serum Amyloid A Protein; D013451:Sulfonic Acids; C008959:lyapolate