Apolipoprotein A-II induces acute-phase response associated AA amyloidosis in mice through conformational changes of plasma lipoprotein structure
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 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.
Article
SCIENTIFIC REPORTS.8:5620(2018)
Journal
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- SCIENTIFIC REPORTS
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SCIENTIFIC REPORTS 8 5620-, 2018-04-04
NATURE PUBLISHING GROUP
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Details 詳細情報について
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- CRID
- 1050005667191173760
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- NII Article ID
- 120007113459
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- ISSN
- 20452322
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- HANDLE
- 10091/00022534
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles