Pharmacological Treatment with Annexin A1 Reduces Atherosclerotic Plaque Burden in LDLR-/- Mice on Western Type Diet.
Pharmacological Treatment with Annexin A1 Reduces Atherosclerotic Plaque Burden in LDLR-/- Mice on Western Type Diet.
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用Annexin A1进行药物治疗可降低西式饮食中LDLR-/-小鼠动脉粥样硬化斑块的负担。
DOI：
10.1371/journal.pone.0130484
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Reutelingsperger CP
中科院分区：
文献类型：
--
作者：
Kusters DH;Chatrou ML;Willems BA;De Saint-Hubert M;Bauwens M;van der Vorst E;Bena S;Biessen EA;Perretti M;Schurgers LJ;Reutelingsperger CP
目的探讨膜联蛋白A1（anxA 1）对低密度脂蛋白受体（LDLR）-/-小鼠动脉粥样硬化形成的治疗作用。利用原核表达系统表达人重组膜联蛋白A1（hr-anxA 1），并对其进行纯化和磷脂酰丝氨酸（PS）结合及甲酰肽受体（FPR）活化分析。测定了99 mTc-hr-anxA 1在C57 Bl/6 J小鼠体内的生物分布。12周龄LDLR-/-小鼠在6周（组I）或12周（组P）期间喂食西式饮食（WTD）。小鼠从WTD开始时（第I组）或WTD开始后6周（第P组）开始，每周腹腔注射3次hr-anxA 1（1 mg/kg）或溶剂，持续6周。采用免疫组化分析总主动脉斑块负荷和表型。Hr-anxA 1以Ca ~（2+）依赖的方式与PS结合，并激活FPR 2/ALX。它能抑制中性粒细胞在活化的内皮细胞上的滚动和粘附，但不能抑制单核细胞。静脉内（IV）和腹膜内（IP）给予hr-anxA 1，循环99 mTc-hr-anxA 1的半衰期分别为<10分钟和约6小时。用hr-anxA 1进行的药物治疗对斑块形成的起始没有显著影响（-33%; P = 0.21）（I组），但显著减弱了主动脉弓和锁骨下动脉的现有斑块的进展（斑块大小-50%，P = 0.005;坏死核心大小-76%P = 0.015，hr-anxA 1 vs媒介物）（P组）。Hr-anxA 1可能通过减少FPR-2依赖的中性粒细胞滚动和粘附到活化的内皮细胞以及通过减少总斑块炎症来提供治疗慢性动脉粥样硬化的药理学手段。
To investigate therapeutic effects of annexin A1 (anxA1) on atherogenesis in LDLR-/- mice. Human recombinant annexin A1 (hr-anxA1) was produced by a prokaryotic expression system, purified and analysed on phosphatidylserine (PS) binding and formyl peptide receptor (FPR) activation. Biodistribution of 99mTechnetium-hr-anxA1 was determined in C57Bl/6J mice. 12 Weeks old LDLR-/- mice were fed a Western Type Diet (WTD) during 6 weeks (Group I) or 12 weeks (Group P). Mice received hr-anxA1 (1 mg/kg) or vehicle by intraperitoneal injection 3 times per week for a period of 6 weeks starting at start of WTD (Group I) or 6 weeks after start of WTD (Group P). Total aortic plaque burden and phenotype were analyzed using immunohistochemistry. Hr-anxA1 bound PS in Ca2+-dependent manner and activated FPR2/ALX. It inhibited rolling and adherence of neutrophils but not monocytes on activated endothelial cells. Half lives of circulating 99mTc-hr-anxA1 were <10 minutes and approximately 6 hours for intravenously (IV) and intraperitoneally (IP) administered hr-anxA1, respectively. Pharmacological treatment with hr-anxA1 had no significant effect on initiation of plaque formation (-33%; P = 0.21)(Group I) but significantly attenuated progression of existing plaques of aortic arch and subclavian artery (plaque size -50%, P = 0.005; necrotic core size -76% P = 0.015, hr-anxA1 vs vehicle) (Group P). Hr-anxA1 may offer pharmacological means to treat chronic atherogenesis by reducing FPR-2 dependent neutrophil rolling and adhesion to activated endothelial cells and by reducing total plaque inflammation.
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影响因子：
20.1
作者：
Drechsler M;de Jong R;Rossaint J;Viola JR;Leoni G;Wang JM;Grommes J;Hinkel R;Kupatt C;Weber C;Döring Y;Zarbock A;Soehnlein O
通讯作者：
Soehnlein O
影响因子：
5.3
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
通讯作者：
Reutelingsperger CP
DOI：
10.1073/pnas.95.24.14535
发表时间：
1998-11-24
影响因子：
11.1
作者：
Lim, LHK;Solito, E;Perretti, M
通讯作者：
Perretti, M
影响因子：
3.5
作者：
De Saint-Hubert, Marijke;Mottaghy, Felix M.;Rattat, Dirk
通讯作者：
Rattat, Dirk
影响因子：
5
作者：
Bot, Ilze;Daissormont, Isabelle T. M. N.;Zernecke, Alma;van Puijvelde, Gijs H. M.;Kramp, Birgit;de Jager, Saskia C. A.;Sluimer, Judith C.;Manca, Marco;Herias, Veronica;Westra, Marijke M.;Bot, Martine;van Santbrink, Peter J.;van Berkel, Theo J. C.;Su, Lishan;Skjelland, Mona;Gullestad, Lars;Kuiper, Johan;Halvorsen, Bente;Aukrust, Paul;Koenen, Rory R.;Weber, Christian;Biessen, Erik A. L.
通讯作者：
Biessen, Erik A. L.