Early increase of specialized pro-resolving lipid mediators in patients with ST-elevation myocardial infarction

EBioMedicine. 2019 Aug;46:264-273. doi: 10.1016/j.ebiom.2019.07.024. Epub 2019 Jul 22.

Abstract

Background: 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.

Methods: 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).

Findings: 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 B4 pathway to the pro-resolving RvTs was observed.

Interpretation: 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.

Keywords: Inflammation; Myocardial infarction; Polyunsaturated fatty acids; Resolution; Specialized pro-resolving mediators.

MeSH terms

  • Aged
  • Biomarkers
  • Case-Control Studies
  • Cytokines / blood
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Lipids / blood*
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / etiology
  • Prospective Studies
  • ST Elevation Myocardial Infarction / blood*
  • ST Elevation Myocardial Infarction / diagnosis
  • ST Elevation Myocardial Infarction / etiology

Substances

  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Lipids