Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8769030 | Translational Research | 2018 | 35 Pages |
Abstract
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.
Keywords
OVLTSFOnAChReNOSIL-10RAASIFN-γnNOSIL-2NTSRVLMTLRDTRAT1RPPAR-γAV3VAT2RWKYSNSIL-8TonEBPRAGIL-13IL-23SCOCVORostroventrolateral medullaMCP-1IL-4iNOSICAM-1IL-6IL-1bROSAngiotensin IIangiotensin type 1 receptorInterleukin-23interleukin-4Interleukin-8Interleukin-10Interleukin-13interleukin-6Interleukin-1 betaInterleukin-2anteroventral third ventricleTAMOrganum vasculosum lamina terminalistumor necrosis factor-alphaToll-like receptorCNSAng IIBBBDendritic cellsinducible nitric oxide synthaseendothelial nitric oxide synthaseneuronal nitric oxide synthaseRenin-angiotensin-aldosterone systemsympathetic nervous systemcentral nervous systemParasympathetic nervous systemShrarea postremaCircumventricular organSubcommissural organVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)TNF-αRecombination Activating GenePVNBlood-brain barrierTumor-associated macrophagesSpontaneously hypertensive ratsNitric oxidenucleus tractus solitariusparaventricular nucleusWistar Kyotoperoxisome proliferator-activated receptor-gammamonocyte chemoattractant protein-1C-reactive proteinCRPChoroid plexusPNSInterferon gammaReactive oxygen speciesadrenergic receptornicotinic acetylcholine receptorDiphtheria Toxin Receptorangiotensin type 2 receptor
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Authors
Sailesh C. Harwani,