Inflammation in acute myocardial infarction: the good, the bad and the ugly
Abstract Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic...
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| Published in: | European heart journal 2024-01, Vol.45 (2), p.89-103 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Abstract
Convergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.e. the smouldering ember of low-grade inflammation persisting in the late phase after AMI. However, these studies have also taught us about potential risks of anti-inflammatory therapy after AMI, particularly related to impaired host defence. Recently, numerous smaller-scale trials have addressed the concept of targeting a deleterious flare of excessive inflammation in the early phase after AMI. Targeting different pathways and implementing various treatment regimens, those trials have met with varied degrees of success. Promising results have come from those studies intervening early on the interleukin-1 and -6 pathways. Taking lessons from such past research may inform an optimized approach to target post-AMI inflammation, tailored to spare ‘The Good’ (repair and defence) while treating ‘The Bad’ (smouldering RIR) and capturing ‘The Ugly’ (flaming early burst of excess inflammation in the acute phase). Key constituents of such a strategy may read as follows: select patients with large pro-inflammatory burden (i.e. large AMI); initiate treatment early (e.g. ≤12 h post-AMI); implement a precisely targeted anti-inflammatory agent; follow through with a tapering treatment regimen. This approach warrants testing in rigorous clinical trials.
Graphical Abstract
Graphical Abstract
‘The Good’, ‘The Bad’, and ‘The Ugly’: Distinct facets of inflammation in acute myocardial infarction (AMI). The left panel (‘The Good’) shows the role of cytokines, T-cells, NKs, and macrophages in myocardial protection and healing. IL-10 and IL-2 reduce pro-inflammatory signals (e.g. TNFα, MCP-1, IL-8), extracellular matrix remodelling (MMP downregulation), while promoting Treg, Th2, and NK activation with subsequent macrophage polarization towards the M2 phenotype. The mid panel (‘The Bad’) represents the smouldering state of low-grade inflammation persisting in the late phase after AMI. Among the protagonist cellular players responsible for ‘The Bad’ are M1-polarized macrophages, foam cells, and PMNs |
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| ISSN: | 0195-668X 1522-9645 |