AnxA5 reduces plaque inflammation of advanced atherosclerotic lesions in apoE(-/-) mice.
AnxA5 reduces plaque inflammation of advanced atherosclerotic lesions in apoE(-/-) mice.
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DOI：
10.1111/jcmm.12374
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发表时间：
2014-10
影响因子：
5.3
通讯作者：
Reutelingsperger CP
中科院分区：
文献类型：
--
作者：
Burgmaier M;Schutters K;Willems B;van der Vorst EP;Kusters D;Chatrou M;Norling L;Biessen EA;Cleutjens J;Perretti M;Schurgers LJ;Reutelingsperger CP
膜联蛋白A5 （AnxA5）通过结合细胞表面表达的磷脂酰丝氨酸发挥抗炎、抗凝和抗凋亡作用。AnxA5在动脉粥样硬化中的作用尚不完全清楚。我们研究了外源性AnxA5对apoE−/−小鼠晚期动脉粥样硬化病变斑块形态和表型的影响。在12周龄的西式饲料喂养的apoE - / -小鼠颈动脉周围放置项圈，诱导晚期动脉粥样硬化病变。5周后，小鼠分别注射AnxA5 （n = 8）或对照物，再注射4周。AnxA5降低了颈动脉晚期粥样硬化病变内膜（59%,P < 0.05）和中膜（73%,P < 0.01）斑块巨噬细胞含量。这些发现证实了主动脉弓的晚期病变，与对照组相比，AnxA5可使斑块巨噬细胞含量减少67% （P < 0.01）。经免疫组化检测，在晚期颈动脉病变中，治疗4周后，AnxA5未改变病变扩展、斑块凋亡、胶原含量、平滑肌细胞含量或脱细胞斑块组成。在体外，AnxA5对巨噬细胞具有抗炎作用，基于流动室的实验表明，AnxA5显著抑制外周血单个核细胞在TNF-α-活化的内皮细胞层上的捕获、滚动、粘附和转运。总之，短期用AnxA5治疗可以减少apoE−/−小鼠晚期病变斑块的炎症，可能是通过干扰炎症病变部位单核细胞的募集和激活。通过靶向暴露的磷脂酰丝氨酸抑制慢性炎症可能成为治疗晚期动脉粥样硬化患者的可行策略。
Annexin A5 (AnxA5) exerts anti-inflammatory, anticoagulant and anti-apoptotic effects through binding cell surface expressed phosphatidylserine. The actions of AnxA5 on atherosclerosis are incompletely understood. We investigated effects of exogenous AnxA5 on plaque morphology and phenotype of advanced atherosclerotic lesions in apoE−/− mice. Advanced atherosclerotic lesions were induced in 12 weeks old Western type diet fed apoE−/− mice using a collar placement around the carotid artery. After 5 weeks mice were injected either with AnxA5 (n = 8) or vehicle for another 4 weeks. AnxA5 reduced plaque macrophage content both in the intima (59% reduction, P < 0.05) and media (73% reduction, P < 0.01) of advanced atherosclerotic lesions of the carotid artery. These findings corroborated with advanced lesions of the aortic arch, where a 67% reduction in plaque macrophage content was observed with AnxA5 compared to controls (P < 0.01). AnxA5 did not change lesion extension, plaque apoptosis, collagen content, smooth muscle cell content or acellular plaque composition after 4 weeks of treatment as determined by immunohistochemistry in advanced carotid lesions. In vitro, AnxA5 exhibited anti-inflammatory effects in macrophages and a flow chamber based assay demonstrated that AnxA5 significantly inhibited capture, rolling, adhesion as well as transmigration of peripheral blood mononuclear cells on a TNF-α-activated endothelial cell layer. In conclusion, short-term treatment with AnxA5 reduces plaque inflammation of advanced lesions in apoE−/− mice likely through interfering with recruitment and activation of monocytes to the inflamed lesion site. Suppressing chronic inflammation by targeting exposed phosphatidylserine may become a viable strategy to treat patients suffering from advanced atherosclerosis.
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影响因子：
37.8
作者：
von der Thüsen, JH;van Berkel, TJC;Biessen, EAL
通讯作者：
Biessen, EAL
影响因子：
24
作者：
Virmani, R;Burke, AP;Kolodgie, FD
通讯作者：
Kolodgie, FD
影响因子：
12.4
作者：
Schutters, K.;Kusters, D. H. M.;Reutelingsperger, C. P. M.
通讯作者：
Reutelingsperger, C. P. M.
影响因子：
37.8
作者：
Lutgens, E;Lutgens, SPM;Cleutjens, KBJM
通讯作者：
Cleutjens, KBJM
影响因子：
7.2
作者：
Schutters, Kristof;Reutelingsperger, Chris
通讯作者：
Reutelingsperger, Chris