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Macrophages under pressure: the role of macrophage polarization in hypertension

  • Sailesh C. Harwani
    Correspondence
    Reprint requests:Division of Cardiovascular Diseases, Department of Internal Medicine, Carver College of Medicine, University of Iowa, 501 Newton Rd., 616B MRC, Iowa City, IA 52242;
    Affiliations
    Department of Internal Medicine, Iowa City, IA

    Center for Immunology and Immune Based Diseases, Iowa City, IA

    Abboud Cardiovascular Research Center, Iowa City, Io
    Search for articles by this author
Published:November 07, 2017DOI:https://doi.org/10.1016/j.trsl.2017.10.011
      Hypertension is a multifactorial disease involving the nervous, renal, and cardiovascular systems. Macrophages are the most abundant and ubiquitous immune cells, placing them in a unique position to serve as key mediators between these components. The polarization of macrophages confers vast phenotypic and functional plasticity, allowing them to act as proinflammatory, homeostatic, and anti-inflammatory agents. Key differences between the M1 and M2 phenotypes, the 2 subsets at the extremes of this polarization spectrum, place macrophages at a juncture to mediate many mechanisms involved in the pathogenesis of hypertension. Neuronal and non-neuronal regulation of the immune system, that is, the “neuroimmuno” axis, plays an integral role in the polarization of macrophages. In hypertension, the neuroimmuno axis results in synchronization of macrophage mobilization from immune cell reservoirs and their chemotaxis, via increased expression of chemoattractants, to end organs critical in the development of hypertension. This complicated system is largely coordinated by the dichotomous actions of the autonomic neuronal and non-neuronal activation of cholinergic, adrenergic, and neurohormonal receptors on macrophages, leading to their ability to “switch” between phenotypes at sites of active inflammation. Data from experimental models and human studies are in concordance with each other and support a central role for macrophage polarization in the pathogenesis of hypertension.

      Abbreviations:

      a7-nAChR (alpha7-nicotinic acetylcholine receptor), Ang II (angiotensin II), AP (area postrema), AR (adrenergic receptor), AT1R (angiotensin type 1 receptor), AT2R (angiotensin type 2 receptor), AV3V (anteroventral third ventricle), BBB (blood-brain barrier), CNS (central nervous system), CP (choroid plexus), CRP (C-reactive protein), CVO (circumventricular organ), DC (dendritic cells), DTR (diphtheria toxin receptor), eNOS (endothelial nitric oxide synthase), ICAM-1 (intercellular adhesion molecule – 1), IFN-γ (interferon gamma), IL-1b (interleukin-1 beta), IL-2 (interleukin-2), IL-4 (interleukin-4), IL-6 (interleukin-6), IL-8 (interleukin-8), IL-10 (interleukin-10), IL-13 (interleukin-13), IL-23 (interleukin-23), iNOS (inducible nitric oxide synthase), MCP-1 (monocyte chemoattractant protein-1), nAChR (nicotinic acetylcholine receptor), nNOS (neuronal nitric oxide synthase), NO (nitric oxide), NTS (nucleus tractus solitarius), OVLT (organum vasculosum lamina terminalis), PNS (parasympathetic nervous system), PPAR-γ (peroxisome proliferator-activated receptor-gamma), PVN (paraventricular nucleus), RAAS (renin-angiotensin-aldosterone system), RAG (recombination activating gene), ROS (reactive oxygen species), RVLM (rostroventrolateral medulla), SCO (subcommissural organ), SFO (subfornical organs), SHR (spontaneously hypertensive rats), SNS (sympathetic nervous system), TAM (tumor-associated macrophages), TLR (toll-like receptor), TNF-α (tumor necrosis factor-alpha), TONEBP (tonicity-enhancer binding protein), VEGF (vascular endothelial growth factor), WKY (Wistar Kyoto)
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