accelerated resolution of aa amyloid in heparanase knockout mice is associated with matrix metalloproteases加速解决heparanase aa淀粉样蛋白的基因敲除小鼠与矩阵metalloproteases相关联.pdfVIP

Accelerated Resolution of AA Amyloid in Heparanase Knockout Mice Is Associated with Matrix Metalloproteases 1 1 1 1 2 3 1 Bo Wang , Ying-xia Tan , Juan Jia , Andreas Digre , Xiao Zhang , Israel Vlodavsky , Jin-ping Li * 1 Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden, 2 Department of Public Health and Caring Sciences, Molecular Geriatrics, University of Uppsala, Uppsala, Sweden, 3 Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel Abstract AA-amyloidosis is a disease characterized by abnormal deposition of serum A amyloid (SAA) peptide along with other components in various organs. The disease is a complication of inflammatory conditions that cause persistent high levels of the acute phase reactant SAA in plasma. In experimental animal models, the deposited amyloid is resolved when the inflammation is stopped, suggesting that there is an efficient clearance mechanism for the amyloid. As heparan sulfate (HS) is one of the major components in the amyloid, its metabolism is expected to affect the pathology of AA amyloidosis. In this study, we investigated the effect of heparanase, a HS degradation enzyme, in resolution of the AA amyloid. The transgenic mice deficient in heparanase (Hpa-KO) produced a similar level of SAA in plasma as the wildtype control (Ctr) mice upon induction by injection of AEF (amyloid enhancing factor) and inflammatory stimuli. The induction resulted in formation of SAA amyloid 7-days post treatment in the spleen that displayed a comparable degree of amyloid load in both groups. The amyloid became significantly less in the Hpa-KO spleen than in the Ctr spleen 10-days post trea