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

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

Author information

1
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. Electronic address: l.e.lillerud@medisin.uio.no.
2
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
3
Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
4
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway.
5
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
6
Department of Medicine, Diakonhjemmet Hospital, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway.
7
Department of Medicine, Diakonhjemmet Hospital, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway.
8
Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; KG Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway.
9
School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, Oslo, Norway.
10
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway; School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
11
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK; Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, UK.
12
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway.

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

PMID:
31345784
DOI:
10.1016/j.ebiom.2019.07.024
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