EFFECT OF POLY(VINYLSULFONATE) ON MURINE AA AMYLOID - A HIGH-RESOLUTION ULTRASTRUCTURAL-STUDY

In experimental murine inflammation-associated amyloidosis (AA amyloid osis), 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 d eposits 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 mic roscopic and high-resolution ultrastructure of amyloid deposits before and after PVS treatment. As shown recently in situ, AA fibrils from u ntreated mice are composed of an outer layer of heparan sulfate proteo glycan and a 1- to 2-nm filament network of AA protein. This layer enc loses a microfibril-like structure composed of chondroitin sulfate pro teoglycan wound around a core of amyloid P component. After treatment with PVS, both the heparan sulfate proteoglycan and the AA filament ne twork are lost from the fibrils, and the more central portion disinteg rates into the chondroitin sulfate proteoglycan with associated amyloi d P subunits. These findings add further support to the concept that h eparan sulfate proteoglycan is important in amyloid fibril structure, and interference with its binding interactions with the amyloid filame nt protein provides a point of therapeutic attack.