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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DOI：
10.1038/s41598-018-23755-y
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发表时间：
2018-04-04
影响因子：
4.6
通讯作者：
Higuchi K
中科院分区：
文献类型：
--
作者：
Yang M;Liu Y;Dai J;Li L;Ding X;Xu Z;Mori M;Miyahara H;Sawashita J;Higuchi K
在急性时相反应(APR)期间，血清淀粉样蛋白A(SAA)在血浆高密度脂蛋白(HDL)中显著升高。在动物和人类中，SAA升高导致反应性AA淀粉样变性。在此，我们利用载脂蛋白A-II缺陷(ApoA-II)缺陷(ApoA_2−/−)和转基因(ApoA_2Tg)小鼠来研究ApoA-II在APR过程中脂蛋白颗粒形成和AA淀粉样变性进展中的潜在作用。与野生型(WT)小鼠相比，ApoA2−/−小鼠AA淀粉样蛋白沉积受到抑制。在APR期间，APOA2−/−小鼠的血清SAA水平和肝脏SAA1和SAA2基因水平均受到显著抑制。病理检查显示，APOA2−/−小鼠在APR过程中组织损伤较轻，炎性细胞浸润较少。ApoA2−/−组小鼠总脂蛋白显著降低，高密度脂蛋白/低密度脂蛋白比值也明显降低。WT和APOA2−/−小鼠在APR期间都表现出低密度脂蛋白和非常大的高密度脂蛋白的升高。在apoA2−/−小鼠中，SAA在从乳糜粒到非常小的高密度脂蛋白的脂蛋白颗粒中分布更广泛。我们的观察揭示了ApoA-II在炎症、血清脂蛋白稳定性和AA淀粉样变性发病率中的关键作用，并促使人们考虑治疗AA和其他淀粉样变性，其前体蛋白与循环中的高密度脂蛋白颗粒相关。
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.
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影响因子：
6.3
作者：
Saka, Bulent;Kaya, Omer;Karan, M. Akif
通讯作者：
Karan, M. Akif
影响因子：
6.3
作者：
Poulia, Kalliopi-Anna;Klek, Stanislaw;Chourdakis, Michael
通讯作者：
Chourdakis, Michael
DOI：
10.1016/j.jamda.2017.07.006
发表时间：
2018-01-01
影响因子：
7.6
作者：
Kim, Sunyoung;Kim, Miji;Won, Chang Won
通讯作者：
Won, Chang Won
影响因子：
6.3
作者：
Rondel, A. L. M. A.;Langius, J. A. E.;Kruizenga, H. M.
通讯作者：
Kruizenga, H. M.
影响因子：
3.8
作者：
Bruyere, O.;Beaudart, C.;Reginster, J. -Y.
通讯作者：
Reginster, J. -Y.