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Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure.

Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure.
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Yang M, Liu Y, Dai J, Li L, Ding X, Xu Z, Mori M, Miyahara H, Sawashita J, Higuchi K,


Yang M, Liu Y, Dai J, Li L, Ding X, Xu Z, Mori M, Miyahara H, Sawashita J, Higuchi K, (click to view)

Yang M, Liu Y, Dai J, Li L, Ding X, Xu Z, Mori M, Miyahara H, Sawashita J, Higuchi K,

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Scientific reports 2018 04 048(1) 5620 doi 10.1038/s41598-018-23755-y

Abstract

During acute-phase response (APR), there is a dramatic increase in serum amyloid A (SAA) in plasma high density lipoproteins (HDL). Elevated SAA leads to reactive AA amyloidosis in animals and humans. Herein, we employed apolipoprotein A-II (ApoA-II) deficient (Apoa2) and transgenic (Apoa2Tg) mice to investigate the potential roles of ApoA-II in lipoprotein particle formation and progression of AA amyloidosis during APR. AA amyloid deposition was suppressed in Apoa2mice compared with wild type (WT) mice. During APR, Apoa2mice exhibited significant suppression of serum SAA levels and hepatic Saa1 and Saa2 mRNA levels. Pathological investigation showed Apoa2mice had less tissue damage and less inflammatory cell infiltration during APR. Total lipoproteins were markedly decreased in Apoa2mice, while the ratio of HDL to low density lipoprotein (LDL) was also decreased. Both WT and Apoa2mice showed increases in LDL and very large HDL during APR. SAA was distributed more widely in lipoprotein particles ranging from chylomicrons to very small HDL in Apoa2mice. Our observations uncovered the critical roles of ApoA-II in inflammation, serum lipoprotein stability and AA amyloidosis morbidity, and prompt consideration of therapies for AA and other amyloidoses, whose precursor proteins are associated with circulating HDL particles.

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