Beneficial effects of quinoline-3-carboxamide (ABR-215757) on atherosclerotic plaque morphology in S100A12 transgenic ApoE null mice.
Beneficial effects of quinoline-3-carboxamide (ABR-215757) on atherosclerotic plaque morphology in S100A12 transgenic ApoE null mice.
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DOI：
10.1016/j.atherosclerosis.2013.02.023
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发表时间：
2013-05
期刊：
影响因子：
5.3
通讯作者：
Bowman, Marion A. Hofmann
中科院分区：
文献类型：
--
作者：
Yan, Ling;Bjork, Per;Butuc, Radu;Gawdzik, Joseph;Earley, Judy;Kim, Gene;Bowman, Marion A. Hofmann
损伤相关分子模式分子(DAMP)S100A8、S100A9和S100A12在心血管疾病和其他疾病中的作用引起了广泛的兴趣。在这项研究中，我们测试了ABR-215757，一种S100蛋白结合的免疫调节化合物，在表达人促炎症S100A12蛋白的转基因载脂蛋白缺失小鼠(SM22α-S100A12)中稳定动脉粥样硬化的有效性。12周龄S100A12转基因/载脂蛋白E-/-和WT/载脂蛋白E-/-转基因小鼠用ABR-21575治疗5周，4个月后进行分析。表面等离子体共振分析表明，S100A12与ABR-215757在体外以锌依赖的方式相互作用。在体内，给予ABR-215757减少了高级斑块形态的特征，导致较小的坏死核，减少了内膜和中层血管钙化，并减少了浸润性炎症细胞的数量。ABR-215757使主动脉RAGE蛋白表达正常化，并使实验诱导的迟发性超敏反应正常化。在表达人S100A12蛋白的载脂蛋白E-/-小鼠中，ABR-215757的作用比在表达人S100A12蛋白的载脂蛋白E-/-小鼠中更显著。我们的数据表明S100A12在动脉粥样硬化的进展中很重要，并且可以被小分子ABR-215757靶向。喹啉-3-羧胺与S100A12的特异性结合减弱了S100A12介导的加速小鼠动脉粥样硬化的特征。
There is an emerging widespread interest in the role of damage-associated molecular pattern molecules (DAMP) S100A8, S100A9 and S100A12 in cardiovascular and other diseases. In this study we tested the efficacy of ABR-215757, a S100 protein binding immuno-modulatory compound to stabilize atherosclerosis in transgenic ApoE null mice that express the human pro-inflammatory S100A12 protein within the smooth muscle cell (SM22α-S100A12). Twelve-week old S100A12 transgenic/ApoE-/- and WT/ApoE-/- mice were treated with ABR-21575 for 5 weeks and were analyzed 4 month later. Surface plasmon resonance analysis demonstrated that S100A12 interacts with ABR-215757 in a zinc dependent manner in vitro. In vivo, ABR-215757 administration reduced features of advanced plaque morphology resulting in smaller necrotic cores, diminished intimal and medial vascular calcification, and reduced amount of infiltrating inflammatory cells. ABR-215757 normalized aortic expression of RAGE protein and normalized experimentally-induced delayed hypersensitivity. The effect of ABR-215757 was more prominent in ApoE-/- mice expressing S100A12 than in ApoE-/- animals lacking expression of human S100A12 protein. Our data suggest that S100A12 is important for progression of atherosclerosis and can be targeted by the small molecule ABR-215757. The specific binding of quinoline-3-carboxamides to S100A12 attenuates S100A12-mediated features of accelerated murine atherosclerosis.
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影响因子：
20.1
作者：
Hofmann Bowman M;Wilk J;Heydemann A;Kim G;Rehman J;Lodato JA;Raman J;McNally EM
通讯作者：
McNally EM
影响因子：
39.2
作者：
Rosenberg S;Elashoff MR;Beineke P;Daniels SE;Wingrove JA;Tingley WG;Sager PT;Sehnert AJ;Yau M;Kraus WE;Newby LK;Schwartz RS;Voros S;Ellis SG;Tahirkheli N;Waksman R;McPherson J;Lansky A;Winn ME;Schork NJ;Topol EJ;PREDICT (Personalized Risk Evaluation and Diagnosis in the Coronary Tree) Investigators
通讯作者：
PREDICT (Personalized Risk Evaluation and Diagnosis in the Coronary Tree) Investigators
影响因子：
37.8
作者：
Croce K;Gao H;Wang Y;Mooroka T;Sakuma M;Shi C;Sukhova GK;Packard RR;Hogg N;Libby P;Simon DI
通讯作者：
Simon DI
影响因子：
5.6
作者：
Carlsten, H;Jonsson, C;Tarkowski, A
通讯作者：
Tarkowski, A
影响因子：
3.9
作者：
Soyfoo, Muhammad S.;Roth, Johannes;Decaux, Guy
通讯作者：
Decaux, Guy