EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice
EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice
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DOI：
10.1093/cvr/cvs225
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发表时间：
2012-10-01
影响因子：
10.8
通讯作者：
Marleau, Sylvie
中科院分区：
文献类型：
--
作者：
Bessi, Valrie L.;Labbe, Sebastien M.;Marleau, Sylvie
CD 36受体在促进脂肪酸转运到心脏中起重要作用。本研究旨在评价EP 80317（一种选择性合成的CD 36肽配体）对小鼠心肌缺血再灌注（MI/R）损伤的保护作用。治疗减少了梗死面积，改善了心肌血流动力学和功能，表现为心输出量、射血分数和每搏作功增加，总外周阻力降低。相反，给予EP 51389（一种缺乏与CD 36结合亲和力的三肽类似物）不能保护心肌免受损伤。心肌再灌注后6小时，EP 80317处理的小鼠显示心肌脂肪酸摄取减少，通过微正电子发射断层扫描评估，与循环非酯化脂肪酸水平降低一致。使用[C-14]-棕榈酸酯输注的研究显示脂解减少，但未观察到胰岛素或儿茶酚胺血浆水平的显著变化。脂肪形成和抗脂解基因的表达水平增加进一步支持EP 80317在防止脂肪酸从脂肪组织动员中的作用。我们的结果表明，EP 80317预处理可保护心脏免受MI/R引起的损伤和功能障碍，沿着外周脂解的短暂减少。我们的研究结果支持CD 36作为治疗缺血性心脏病的新靶点。
The CD36 receptor plays an important role in facilitating fatty acid transport to the heart. The present study aimed to assess whether EP 80317, a selective synthetic peptide ligand of CD36, is cardioprotective in a murine model of myocardial ischaemia and reperfusion (MI/R) injury.Mice were pretreated with daily subcutaneous injections of EP 80317 for 14 days before being subjected to a 30 min ligation of the left anterior descending coronary artery. The treatment reduced the infarct area and improved myocardial haemodynamics and function, as shown by an increase in cardiac output, ejection fraction and stroke work, and a reduced total peripheral resistance. In contrast, administration of EP 51389, a tripeptide analogue devoid of binding affinity to CD36, did not protect against myocardial injury. Six hours after myocardial reperfusion, EP 80317-treated mice showed reduced myocardial fatty acid uptake, as assessed by micro-positron emission tomography, in agreement with reduced levels of circulating non-esterified fatty acids. Studies using [C-14]-palmitate infusion revealed reduced lipolysis, although no significant change in insulin or catecholamine plasma levels were observed. Increased expression levels of adipogenic and anti-lipolytic genes further supported an effect of EP 80317 in preventing fatty acid mobilization from adipose tissue. No effect of the treatment was observed in CD36(/) mice.Our results show that pretreatment with EP 80317 protected the heart against damage and dysfunction elicited by MI/R, along with a transient reduction in peripheral lipolysis. Our findings support CD36 as a novel target for the treatment of ischaemic cardiopathy.