Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Medicine, Diakonhjemmet Hospital, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
EBioMedicine. 2019 Aug;46:264-273. doi: 10.1016/j.ebiom.2019.07.024. Epub 2019 Jul 22.
Termination of acute inflammation is an active process orchestrated by lipid mediators (LM) derived from polyunsaturated fatty acids, referred to as specialized pro-resolving mediators (SPM). These mediators also provide novel therapeutic opportunities for treating inflammatory disease. However, the regulation of these molecules following acute myocardial infarction (MI) remains of interest.
In this prospective observational study we aimed to profile plasma levels of SPMs in ST-elevation MI (STEMI) patients during the first week following MI. Plasma LM concentrations were measured in patients with STEMI (n = 15) at three time points and compared with stable coronary artery disease (CAD; n = 10) and healthy controls (n = 10).
Our main findings were: (i) Immediately after onset of MI and before peak troponin T levels, STEMI patients had markedly increased levels of SPMs as compared with healthy controls and stable CAD patients, with levels of these mediators declining during follow-up. (ii) The increase in SPMs primarily reflected an increase in docosapentaenoic acid- and docosahexaenoic acid-derived protectins. (iii) Several individual protectins were correlated with the rapid increase in neutrophil counts, but not with CRP. (iv) A shift in 5-LOX activity from the leukotriene B pathway to the pro-resolving RvTs was observed.
The temporal regulation of SPMs indicates that resolution mechanisms are activated early during STEMI as part of an endogenous mechanism to initiate repair. Thus strategies to boost the activity and/or efficacy of these endogenous mechanisms may represent novel therapeutic opportunities for treatment of patients with MI. FUND: This work was supported by grants from the South-Eastern Norwegian regional health authority, the European Research Council under the European Union's Horizon 2020 research and innovation program, a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society, and the Barts Charity.
急性炎症的终止是由多不饱和脂肪酸衍生的脂质介质（LM），即所谓的专门的促解决介质（SPM）协调的主动过程。这些介质也为治疗炎症性疾病提供了新的治疗机会。然而，急性心肌梗死（MI）后这些分子的调节仍然是一个研究热点。
在这项前瞻性观察研究中，我们旨在分析 MI 后第一周 ST 段抬高型心肌梗死（STEMI）患者的 SPM 血浆水平谱。在三个时间点测量了 STEMI 患者（n=15）和稳定型冠心病（CAD；n=10）和健康对照组（n=10）的血浆 LM 浓度。
我们的主要发现是：（i）在 MI 发作后且在肌钙蛋白 T 峰值之前，STEMI 患者的 SPM 水平明显高于健康对照组和稳定型 CAD 患者，这些介质的水平在随访期间下降。（ii）SPM 的增加主要反映了二十二碳五烯酸和二十二碳六烯酸衍生的保护素的增加。（iii）几种个体保护素与中性粒细胞计数的快速增加相关，但与 CRP 无关。（iv）观察到 5-LOX 活性从白三烯 B 途径向促解决 RvTs 的转移。
SPM 的时间调节表明，在 STEMI 早期就激活了解决机制，作为启动修复的内源性机制的一部分。因此，增强这些内源性机制的活性和/或功效的策略可能代表治疗 MI 患者的新治疗机会。
这项工作得到了挪威东南地区卫生当局、欧盟地平线 2020 研究和创新计划下的欧洲研究理事会、惠康信托基金会和英国皇家学会共同资助的亨利·戴尔爵士奖学金以及 Barts 慈善基金会的支持。
