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

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.

• Authors: Linn E Fosshaug, Romain A Colas, Anne K Anstensrud, Ida Gregersen, Ståle Nymo, Ellen L Sagen, Annika Michelsen, Leif E Vinge, Erik Øie, Lars Gullestad, Bente Halvorsen, Trond V Hansen, Pål Aukrust, Jesmond Dalli, Arne Yndestad
• Journal: EBioMedicine (EBioMedicine) Vol. 46 Pg. 264-273 (Aug 2019) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 31345784 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Cytokines
• Inflammation Mediators
• Lipids

Topics

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