Hematopoietic miR155 deficiency enhances atherosclerosis and decreases plaque stability in hyperlipidemic mice.
Hematopoietic miR155 deficiency enhances atherosclerosis and decreases plaque stability in hyperlipidemic mice.
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DOI：
10.1371/journal.pone.0035877
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
de Winther MP
中科院分区：
文献类型：
--
作者：
Donners MM;Wolfs IM;Stöger LJ;van der Vorst EP;Pöttgens CC;Heymans S;Schroen B;Gijbels MJ;de Winther MP
microRNA-155（miR 155）是由炎症介质诱导的免疫应答的中心调节因子。尽管miR 155被认为是一种促炎microRNA，但体外报告显示其在脂质负载细胞中具有抗炎作用。在这项研究中，我们研究了miR 155在动脉粥样硬化中的作用，在体内骨髓移植miR 155缺陷或野生型小鼠高脂血症小鼠。miR 155的造血缺陷增强动脉粥样硬化斑块的发展并降低斑块稳定性，如通过增加骨髓炎性细胞向斑块的募集所证明的。增加的炎症状态反映在miR 155 −/−移植小鼠血液中循环CD 4 + CD 25 + FoxP 3+调节性T细胞的减少和粒细胞（CD 11b + Ly 6 G+）的增加。此外，我们首次显示了miR 155在单核细胞亚群分化中的关键作用，因为miR 155的造血缺陷增加了循环中的“炎性”单核细胞亚群（CD 11b + Ly 6 G-Ly 6Chi）并减少了“常驻”单核细胞（CD 11b + Ly 6 G-Ly 6Clow）。此外，由于抗炎性IL-10的产生减少，miR 155 −/−移植的高脂血症小鼠的常驻腹膜巨噬细胞的细胞因子产生偏向于更促炎的状态。总之，在这种高脂血症小鼠模型中，miR 155作为抗炎、动脉粥样硬化保护性microRNA发挥作用。此外，除了在淋巴细胞发育中的已知作用外，我们还显示了miR 155在髓系分化中的关键作用。
microRNA-155 (miR155) is a central regulator of immune responses that is induced by inflammatory mediators. Although miR155 is considered to be a pro-inflammatory microRNA, in vitro reports show anti-inflammatory effects in lipid-loaded cells. In this study we examined the role of miR155 in atherosclerosis in vivo using bone marrow transplantation from miR155 deficient or wildtype mice to hyperlipidemic mice. Hematopoietic deficiency of miR155 enhanced atherosclerotic plaque development and decreased plaque stability, as evidenced by increased myeloid inflammatory cell recruitment to the plaque. The increased inflammatory state was mirrored by a decrease in circulating CD4+CD25+FoxP3+ regulatory T cells, and an increase in granulocytes (CD11b+Ly6G+) in blood of miR155−/− transplanted mice. Moreover, we show for the first time a crucial role of miR155 in monocyte subset differentiation, since hematopoietic deficiency of miR155 increases the ‘inflammatory’ monocyte subset (CD11b+Ly6G−Ly6Chi) and reduces ‘resident’ monocytes (CD11b+Ly6G−Ly6Clow) in the circulation. Furthermore, cytokine production by resident peritoneal macrophages of miR155−/− transplanted hyperlipidemic mice was skewed towards a more pro-inflammatory state since anti-inflammatory IL-10 production was reduced. In conclusion, in this hyperlipidemic mouse model miR155 acts as an anti-inflammatory, atheroprotective microRNA. Additionally, besides a known role in lymphoid cell development, we show a crucial role of miR155 in myeloid lineage differentiation.
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影响因子：
32.4
作者：
O'Connell RM;Kahn D;Gibson WS;Round JL;Scholz RL;Chaudhuri AA;Kahn ME;Rao DS;Baltimore D
通讯作者：
Baltimore D
DOI：
10.1126/science.1139253
发表时间：
2007-04-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rodriguez A;Vigorito E;Clare S;Warren MV;Couttet P;Soond DR;van Dongen S;Grocock RJ;Das PP;Miska EA;Vetrie D;Okkenhaug K;Enright AJ;Dougan G;Turner M;Bradley A
通讯作者：
Bradley A
影响因子：
4.4
作者：
Ding, YZ;Chen, DM;Bromberg, JS
通讯作者：
Bromberg, JS
影响因子：
3.7
作者：
Goossens P;Vergouwe MN;Gijbels MJ;Curfs DM;van Woezik JH;Hoeksema MA;Xanthoulea S;Leenen PJ;Rupec RA;Hofker MH;de Winther MP
通讯作者：
de Winther MP
影响因子：
32.4
作者：
Lu, Li-Fan;Thai, To-Ha;Calado, Dinis Pedro;Chaudhry, Ashutosh;Kubo, Masato;Tanaka, Kentaro;Loeb, Gabriel B.;Lee, Hana;Yoshimura, Akihiko;Rajewsky, Klaus;Rudensky, Alexander Y.
通讯作者：
Rudensky, Alexander Y.