Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action
Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action
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DOI：
10.1096/fj.01-0196com
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发表时间：
2001-10-01
期刊：
影响因子：
4.8
通讯作者：
Perretti, M
中科院分区：
文献类型：
--
作者：
La, M;D'Amico, M;Perretti, M
心肌再灌注损伤与血传多形核白细胞浸润有关。我们先前已经描述了膜联蛋白1（ANXA 1）在大鼠心肌缺血再灌注（IR）损伤的实验模型中提供的保护。我们检查了1）在大鼠心脏IR模型中保留保护作用的ANXA 1的氨基酸区域; 2）与IR诱导的损伤和药理学调节后相关的内源性ANXA 1的变化;以及3）甲酰肽受体（FPR）在ANXA 1肽显示的保护作用中的潜在参与。在再灌注后0、30和60分钟给予Ac 2 -26肽可显著保护IR损伤，这与梗死心脏中髓过氧化物酶活性和IL-1 β水平降低有关。Western blotting和电镜分析显示，IR心脏损伤组织中ANXA 1表达增加，主要与浸润的白细胞有关。最后，FPR受体的拮抗剂选择性地抑制肽ANXA 1及其衍生肽对IR损伤的保护作用。总之，这些数据为ANXA 1及其模拟物的保护作用提供了进一步的见解，并为从这一研究领域开发的药物的临床应用提供了理论基础。
Myocardial reperfusion injury is associated with the infiltration of blood-borne polymorphonuclear leukocytes. We have previous described the protection afforded by annexin 1 (ANXA1) in an experimental model of rat myocardial ischemia-reperfusion (IR) injury. We examined the 1) amino acid region of ANXA1 that retained the protective effect in a model of rat heart IR; 2) changes in endogenous ANXA1 in relation to the IR induced damage and after pharmacological modulation; and 3) potential involvement of the formyl peptide receptor (FPR) in the protective action displayed by ANXA1 peptides. Administration of peptide Ac2-26 at 0, 30, and 60 min postreperfusion produced a significant protection against IR injury, and this was associated with reduced myeloperoxidase activity and IL-1 beta levels in the infarcted heart. Western blotting and electron microscopy analyses showed that IR heart had increased ANXA1 expression in the injured tissue, associated mainly with the infiltrated leukocytes. Finally, an antagonist to the FPR receptor selectively inhibited the protective action of peptide ANXA1 and its derived peptides against IR injury. Altogether, these data provide further insight into the protective effect of ANXA1 and its mimetics and a rationale for a clinical use for drugs developed from this line of research.