Key Laboratory of Food Safety Research, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Department of Pharmacology, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Br J Pharmacol. 2018 Apr;175(8):1205-1216. doi: 10.1111/bph.14041. Epub 2017 Oct 22.
An appropriate inflammatory response is necessary for cardiac healing after acute myocardial infarction (MI). Resolvin E1 (RvE1) is an anti-inflammatory and pro-resolution lipid mediator derived from eicosapentaenoic acid. Here we have investigated the effects of RvE1 on the recovery of cardiac function after MI in mice.
Acute MI was induced by surgical ligation of the left anterior descending artery in male C57BL/6 mice. RvE1 (5 ng·g ·day ; i.p.) was given to mice at different times following MI. Cardiac function was monitored by transthoracic echocardiography at days 3, 7 and 14 after MI. Effects of RvE1 on the migration of subpopulations of monocytes/macrophages (Mos/Mps, Ly6C and Ly6C ) were examined by flow cytometry and transwell assay.
RvE1 administration from days 1 to 7 post-MI improved cardiac function, whereas treatment from days 7 to 14 markedly inhibited recovery of cardiac function. Early treatment with RvE1 post-MI suppressed the infiltration of dominant Ly6C Mos/Mps and secretion of pro-inflammatory cytokines in injured hearts, which protected cardiomyocytes against apoptosis in the peri-infarct zones. Contrastingly, treatment with RvE1 1 week after MI decreased infiltration of Ly6C Mos/Mps and expression of pro-angiogenic factors in cardiac tissue, consequently reducing neovascularization in the peri-infarct zones. Additionally, RvE1 inhibited Mp migration by activating ChemR23 receptors.
Treatment with RvE1 during the initial 7 days after MI facilitated cardiac healing by suppressing pro-inflammatory cytokine secretion, indicating that RvE1 may serve as an early therapeutic agent for acute MI.
This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
适当的炎症反应对于急性心肌梗死（MI）后的心脏愈合是必要的。Resolvin E1（RvE1）是一种源自二十碳五烯酸的抗炎和促解决脂质介质。在这里，我们研究了 RvE1 对 MI 后小鼠心脏功能恢复的影响。
通过手术结扎雄性 C57BL/6 小鼠的左前降支诱导急性 MI。MI 后不同时间给予 RvE1（5ng·g·天；腹腔注射）。MI 后 3、7 和 14 天通过经胸超声心动图监测心脏功能。通过流式细胞术和 Transwell 测定法检查 RvE1 对单核细胞/巨噬细胞（Mos/Mps、Ly6C 和 Ly6C）亚群迁移的影响。
MI 后第 1 至 7 天给予 RvE1 可改善心脏功能，而第 7 至 14 天给予 RvE1 则明显抑制心脏功能的恢复。MI 后早期给予 RvE1 可抑制损伤心脏中主导 Ly6C Mos/Mps 的浸润和促炎细胞因子的分泌，从而保护梗死周边区的心肌细胞免受细胞凋亡。相反，MI 后 1 周给予 RvE1 可减少 Ly6C Mos/Mps 的浸润和心脏组织中促血管生成因子的表达，从而减少梗死周边区的新生血管形成。此外，RvE1 通过激活 ChemR23 受体抑制 Mp 迁移。
MI 后最初 7 天给予 RvE1 治疗可通过抑制促炎细胞因子的分泌促进心脏愈合，表明 RvE1 可能成为急性 MI 的早期治疗药物。
本文是心血管疾病小分子重点关注专题的一部分。要查看本专题中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc。
