Open AccessApolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure
Author(s) -
Yang Mi,
Yingye Liu,
Jian Dai,
Lin Li,
Xiaoyan Ding,
Zhe Xu,
Masayuki Mori,
Hiroki Miyahara,
Jinko Sawashita,
Kenichi Higuchi
Publication year - 2018
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-018-23755-y
Subject(s) - serum amyloid a , medicine , apolipoprotein b , lipoprotein , endocrinology , amyloidosis , chemistry , acute phase protein , inflammation , serum amyloid a protein , high density lipoprotein , pathological , amyloid (mycology) , apolipoprotein e , cholesterol , disease , inorganic chemistry
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 ( Apoa2 Tg) 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 Apoa2 −/− mice compared with wild type (WT) mice. During APR, Apoa2 −/− mice exhibited significant suppression of serum SAA levels and hepatic Saa1 and Saa2 mRNA levels. Pathological investigation showed Apoa2 −/− mice had less tissue damage and less inflammatory cell infiltration during APR. Total lipoproteins were markedly decreased in Apoa2 −/− mice, while the ratio of HDL to low density lipoprotein (LDL) was also decreased. Both WT and Apoa2 −/− mice 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 Apoa2 −/− mice. 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.