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  • Review Article
  • Published:

Monocytes and macrophages in abdominal aortic aneurysm

Nature Reviews Cardiology volume 14, pages 457–471 (2017)Cite this article

Subjects

Key Points

  • Most of the macrophages that accumulate in the aneurysmal aortic wall originate from circulating monocytes; however, some macrophages in abdominal aortic aneurysms (AAAs) might originate from aortic tissue-resident macrophages

  • The main factors involved in macrophage accumulation in the AAA wall include chemokines and cytokines produced in response to tissue injury, products of extracellular matrix degradation, and microenvironmental conditions

  • Monocytes and macrophages have distinct phenotypes during the development and progression of AAA, with major implications for monocyte and macrophage activation and biological functions in AAA

  • Macrophages have both pathogenic and reparative roles in AAA through their involvement in extracellular matrix remodelling, in promotion and resolution of inflammation, and in various aspects of the tissue-healing response

  • State-of-the-art translational applications are available that can be improved and harnessed for the use of monocytes and macrophages as diagnostic and prognostic biomarkers, and as therapeutic targets in AAA

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high morbidity, and high mortality in the event of aortic rupture. Major advances in open surgical and endovascular repair of AAA have been achieved during the past 2 decades. However, drug-based therapies are still lacking, highlighting a real need for better understanding of the molecular and cellular mechanisms involved in AAA formation and progression. The main pathological features of AAA include extracellular matrix remodelling associated with degeneration and loss of vascular smooth muscle cells and accumulation and activation of inflammatory cells. The inflammatory process has a crucial role in AAA and substantially influences many determinants of aortic wall remodelling. In this Review, we focus specifically on the involvement of monocytes and macrophages, summarizing current knowledge on the roles, origin, and functions of these cells in AAA development and its complications. Furthermore, we show and propose that distinct monocyte and macrophage subsets have critical and differential roles in initiation, progression, and healing of the aneurysmal process. On the basis of experimental and clinical studies, we review potential translational applications to detect, assess, and image macrophage subsets in AAA, and discuss the relevance of these applications for clinical practice.

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Figure 1: Origin of macrophages in the aneurysmal aortic wall.
Figure 2: Role of macrophages in AAA and main factors modulating macrophage activity.
Figure 3: Hypothesized roles of monocyte and macrophage subsets in AAA pathogenesis.

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Acknowledgements

The authors are supported by the British Heart Foundation and the European Research Council. We apologise for being unable to discuss all the relevant papers owing to space limitations.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, West Forvie Building, Forvie Site, Robinson Way, CB2 0SZ, Cambridge, UK

    Juliette Raffort, Fabien Lareyre, Marc Clément & Ziad Mallat

  2. Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, 56 rue Leblanc, Paris, 75015, France

    Juliette Raffort & Ziad Mallat

  3. Clinical Chemistry Laboratory, University Hospital of Nice, Hôpital Pasteur, 30 Voie Romaine, Nice Cedex 1, 06006, France

    Juliette Raffort & Giulia Chinetti

  4. Université Côte d'Azur, CHU, CNRS, Inserm, IRCAN, Tour Pasteur, Avenue de Valombrose, Nice, 06107, France

    Juliette Raffort, Fabien Lareyre, Réda Hassen-Khodja & Giulia Chinetti

  5. Department of Vascular Surgery, University Hospital of Nice, Hôpital Pasteur, 30 Voie Romaine, 06006, Nice Cedex 1, France

    Fabien Lareyre & Réda Hassen-Khodja

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Contributions

J.R., F.L., and Z.M. researched the data for the article. J.R., F.L., M.C., and Z.M. wrote the article. All authors provided substantial contributions to discussions of content and reviewed/edited the manuscript before submission.

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PowerPoint slides

Glossary

Efferocytosis

Process by which apoptotic cells are removed by phagocytic cells.

Podosomes

Actin-based structures that dynamically protrude from the plasma membrane, and are recognized as prominent sites of attachment to, and degradation of, the extracellular matrix.

Canonical inflammasome pathway

Innate immune system receptors/sensors that promote the maturation of IL-1β through the activation of caspase 1.

High-mobility group protein B1

Nonhistone nuclear protein that regulates gene expression; can be translocated to the cytosol and secreted as a pro-inflammatory mediator through activation of Toll-like receptors or advanced glycosylation end-products receptors.

Matrix crosslinking

Process by which chemical bonds are formed between adjacent molecules composing the matrix.

Somatostatin receptors

G-protein-coupled receptors that are expressed in various tissues including the central nervous system, immune system, and gastrointestinal tissues. Somatostatin receptor type 2 is highly expressed on macrophages that accumulate in inflammatory tissues.

Evasins

Class of chemokine-binding proteins, initially isolated from salivary glands of ticks, that can inhibit chemokine binding to their receptors, and might have either a narrow or a broad binding spectrum.

D-series resolvins

Family of mediators derived from omega-3 essential fatty acid precursors; involved in the resolution phase of inflammation.

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Raffort, J., Lareyre, F., Clément, M. et al. Monocytes and macrophages in abdominal aortic aneurysm. Nat Rev Cardiol 14, 457–471 (2017). https://doi.org/10.1038/nrcardio.2017.52

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