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Mast cells in human and experimental cardiometabolic diseases

Nature Reviews Cardiology volume 12, pages 643–658 (2015)Cite this article

Subjects

Key Points

  • The number of activated mast cells is increased in the coronary arteries, myocardium, aorta, and adipose tissue of patients with cardiometabolic diseases and associated complications

  • Mast-cell activation occurs when ligands such as IgE, IgG, lipopolysaccharide, complement peptides C3a and C5a, substance P, or neuropeptide Y interact with their respective receptors on the cell surface

  • Mast-cell activation results in the release of chemokines, cytokines, histamine, proteases, and many other mediators, which can contribute to the pathogenesis of human and experimental cardiometabolic diseases

  • Genetic depletion or pharmacological inactivation of mast cells confers protection from cardiometabolic pathologies in animal models

  • Genetic deficiency or pharmacological inhibition of mast cell mediators also confers protection from cardiometabolic pathologies in animal models

  • Common anti-allergy drugs that either stabilize mast cells or prevent their activation (for example, anti-IgE antibodies) are effective in ameliorating cardiometabolic diseases in animal models and potentially in humans

Abstract

Mast cells, like many other types of inflammatory cell, perform pleiotropic roles in cardiometabolic diseases such as atherosclerosis, abdominal aortic aneurysms, obesity, and diabetes mellitus, as well as complications associated with these diseases. Low numbers of mast cells are present in the heart, aorta, and adipose tissue of healthy humans, but patients with cardiometabolic diseases and animals with experimentally-induced cardiometabolic pathologies have high numbers of mast cells with increased activity in the affected tissues. Mediators released by the activated mast cells, such as chemokines, cytokines, growth factors, heparin, histamine, and proteases, not only function as biomarkers of cardiometabolic diseases, but might also directly contribute to the pathogenesis of such diseases. Mast-cell mediators impede the functions of vascular cells, the integrity of the extracellular matrix, and the activity of other inflammatory cells, thereby contributing to the pathobiology of the conditions at multiple levels. In mouse models, mast-cell activation aggravates the progression of various cardiometabolic pathologies, whereas a genetic deficiency or pharmacological stabilization of mast cells, or depletion or inhibition of specific mast-cell mediators, tends to delay the progression of such conditions. Pharmacological inhibition of mast-cell activation or their targeted effector functions offers potential novel therapeutic strategies for patients with cardiometabolic disorders.

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Figure 1: Mast cells in normal and atherosclerotic lesions.
Figure 2: Pathways leading to the activation of mast cells during the development and progression of atherosclerosis.
Figure 3: Mast-cell-mediated foam-cell formation in the arterial intima on activation.
Figure 4: Proatherogenic effects of mast cells and their important mediators in the arterial wall.
Figure 5: Mast cells and their mediators in the pathogenesis of AAAs.
Figure 6: Mast cells in obese and lean individuals.
Figure 7: Localization of mast cells and their progenitors in lean and obese WAT of mice.

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Acknowledgements

The authors are supported by National Institutes of Health grants HL60942, HL81090, HL88547 (G.-P.S.), and a Dr Dekker Senior Postdoc grant from the Netherlands Heart Foundation (2012T083) (I.B.). Wihuri Research Institute is maintained by the Jenny and Antti Wihuri Foundation.

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Authors and Affiliations

  1. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, 02115, MA, USA

    Guo-Ping Shi

  2. Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands

    Ilze Bot

  3. Wihuri Research Institute, Biomedicum Helsinki 1, Helsinki, 00290, Finland

    Petri T. Kovanen

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All the authors researched data for the article, discussed its content, wrote the manuscript, and reviewed/edited it before submission.

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Correspondence to Petri T. Kovanen.

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Shi, GP., Bot, I. & Kovanen, P. Mast cells in human and experimental cardiometabolic diseases. Nat Rev Cardiol 12, 643–658 (2015). https://doi.org/10.1038/nrcardio.2015.117

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