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The effect of macrophage-targeted interventions on blood pressure - a systematic review and meta-analysis of preclinical studies.

Authors
  • Wenstedt, Eliane F E1
  • van Croonenburg, Thirza J1
  • van den Born, Bert-Jan H2
  • Van den Bossche, Jan3
  • Hooijmans, Carlijn R4
  • Vogt, Liffert5
  • 1 Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. , (Netherlands)
  • 2 Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Section of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. , (Netherlands)
  • 3 Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, Amsterdam, The Netherlands. , (Netherlands)
  • 4 Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands. , (Netherlands)
  • 5 Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Section of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. Electronic address: [email protected] , (Netherlands)
Type
Published Article
Journal
Translational research : the journal of laboratory and clinical medicine
Publication Date
Apr 01, 2021
Volume
230
Pages
123–138
Identifiers
DOI: 10.1016/j.trsl.2020.11.002
PMID: 33166696
Source
Medline
Language
English
License
Unknown

Abstract

An increasing body of evidence shows a role for macrophages and monocytes (as their precursors) in hypertension, but with conflicting results with regard to whether they are protective or harmful. Therefore, we systematically reviewed the effect of macrophage interventions on blood pressure in animal models, to explore which factors determine the blood pressure increasing vs. decreasing effect. A search in PubMED and EMBASE yielded 9620 records, 26 of which were included. Eighteen studies (involving 22 different experiments (k = 22)) performed macrophage depletion, whereas 12 studies specifically deleted certain macrophage proteins. The blood pressure effects of macrophage depletion were highly various and directed toward both directions, as expected, which could not be reduced to differences in animal species or methods of hypertension induction. Prespecified subgroup analysis did reveal a potential role for the route in which the macrophage-depleting agent is being administrated (intraperitoneal vs intravenous subgroup difference of P = 0.07 (k = 22), or P < 0.001 in studies achieving considerable (ie, >50%) depletion (k = 18)). Along with findings from specific macrophage protein deletion studies-showing that deletion of one single macrophage protein (like TonEBP, endothelin-B, EP4, NOX-2 and the angiotensin II type 1 receptor) can alter blood pressure responses to hypertensive stimuli-the indication that each route has its specific depletion pattern regarding targeted tissues and macrophage phenotypes suggests a determinative role for these features. These hypothesis-generating results encourage more detailed depletion characterization of each technique by direct experimental comparisons, providing a chance to obtain more knowledge on which macrophages are beneficial versus detrimental in hypertension development. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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