Review articleMonocyte and macrophage subsets along the continuum to heart failure: Misguided heroes or targetable villains?
Section snippets
Cardiovascular disease and inflammation
Diseases of the cardiovascular system including ischaemic heart disease, cerebrovascular disease, hypertension, heart failure (HF) and rheumatic disease are the underlying cause for 29.2% (16.7 million) of total global deaths annually according to statistics of the World Health Organization. Approximately a quarter of all deaths occur as a result of chronic diseases including HF, with equal contribution of HF with Preserved and Reduced Ejection Fraction (HFPEF and HFREF). Insufficient knowledge
Monocytes and macrophages — the effector cells of inflammation and coordinators of wound healing in cardiovascular disease and heart failure
Monocytes are components of the innate and adaptive immune systems with primary functions in immune defence, inflammation and tissue remodelling. As regulators of immune responses, monocytes protect the host against foreign pathogens in a non-antigen-specific manner either by direct pathogen elimination (depending on specific interactions between pattern recognition receptors including toll-like receptors (TLR), the lipopolysaccharide co-receptor CD14, and scavenger receptors) or by production
Monocyte and macrophage subsets
At least three subsets of monocytes with distinct phenotypic and functional characteristics exist in human peripheral blood (Fig. 1).
Monocyte subsets are best differentiated on the basis of surface expression of the lipopolysaccharide co-receptor CD14 and the Fcγ receptor III CD16 and are classified as classical, CD14 ++CD16 −, intermediate CD14 ++CD16 +, or alternative, CD14 + CD16 ++ monocytes [38], [39]. Classical monocytes make up for approximately 85–90% of all blood monocytes whilst
Monocyte and macrophage subsets in animal models and patients with CVD and heart failure
A limited number of pre-clinical and clinical studies have been performed to characterize monocyte subsets in the blood of patients with cardiovascular disease and HF and study the contribution of these to the pathophysiology of HF (Table 1).
Most pre-clinical studies examining monocyte subtype and function pertain to animal models of atherosclerosis and myocardial infarction. Nahrendorf et al. described that the healing process in the mouse heart following myocardial infarction requires
Monocyte and macrophage-based therapeutic approaches in heart disease and failure
Given the importance of monocyte/macrophage heterogeneity and multi-functionality, the concepts of monocyte/macrophage plasticity and manipulation for therapeutic application in the fields of chronic inflammatory diseases and cancer are gaining considerable scientific and clinical interest. Unfortunately, due to the complexity and subtlety of the field, the literature is rather limited [46], [67].
Ample evidence has shown beneficial effects of blocking monocyte/macrophage infiltration and
Summary
When considering the role of monocytes and macrophages in the progression to heart failure (Fig. 2) it is clear that any therapeutic intervention has to be targeted specifically to the stage and type of disease.
From a simplistic model point of view it would be apparent that attenuating M1 macrophage activity immediately following myocardial infarction has the potential to minimize tissue injury and cell damage that may be caused by an uncontrolled M1-driven response. However, given the
Conclusion
The monocyte/macrophage system is an important innate immune mechanism to battle infection and malignancy. A perhaps equally important function is its regulation and tuning of inflammatory, wound repair and fibrotic processes and therefore tissue remodelling and repair in systemic diseases including cardiovascular disease. Here we summarize the most recent knowledge on monocytes and macrophages in the field of cardiac inflammation, cardiac fibrosis and heart failure including novel findings on
Disclosures
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Acknowledgements
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2018, Redox BiologyCitation Excerpt :The engagement of TLR proteins at the surface of myeloid, epithelial and endothelial cells by PAMPs or DAMPs, and the subsequent activation of NF-kB-dependent gene expression are key initiating events in the inflammatory response [7]. However, exaggerated or chronic activation of this pathway contributes to tissue injury and can lead to disease development [6,38,39]. In this regard, translation of Nrf2-dependent genes is crucial for cell survival in the presence of inflammation-derived oxygen and nitrogen reactive species [40].
Physiological proteomics of heart failure
2018, Current Opinion in PhysiologyCitation Excerpt :Heightened systemic inflammation plays an important role in determining the outcome of MI and hypertension; thus, inflammation serves as a common mediator. The complex role of inflammation in driving tissue injury and fibrosis in HF has been extensively highlighted [12••,13,14], but the full potential of these pathways as therapeutic targets has not been realized due to the need for greater understanding of cell type-specific and tissue-specific functions. Transcriptomic approaches have revealed a wealth of cell type-specific and tissue-specific information about local and systemic responses to cardiac injury, but it is apparent that such analyses do not account for the complexity of protein structure and function.
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Present address for Stephen Horgan is Brigham and Women's Hospital, Boston, Massachusetts, USA.