PMID- 35155614
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 8
DP  - 2021
TI  - Macrophages Can Drive Sympathetic Excitability in the Early Stages of 
      Hypertension.
PG  - 807904
LID - 10.3389/fcvm.2021.807904 [doi]
LID - 807904
AB  - Hypertension is a major health burden worldwide with many cases resistant to 
      current treatments. Hyperactivity of the sympathetic nervous contributes to the 
      etiology and progression of the disease, where emerging evidence suggests that 
      inflammation may underpin the development of sympathetic dysautonomia. This study 
      examined whether macrophages could drive the sympathetic phenotype in 
      Spontaneously Hypertensive Rats (SHR) before animals develop high pressure. 
      Stellate neurons from wild-type control Wistar rats and SHRs were co-cultured 
      with blood leukocytes from their own strain, and also crossed cultured between 
      strains. The calcium transient response to nicotinic stimulation was recorded 
      using Fura-2 calcium imaging, where SHR neurons had a greater calcium transient 
      compared with Wistar neurons. However, when co-cultured with leukocytes, Wistar 
      neurons began to phenocopy the SHR sympathetic hyperactivity, while the SHR 
      neurons themselves were unaltered. Resident leukocyte populations of the SHR and 
      Wistar stellate ganglia were then compared using flow cytometry, where there was 
      a shift in monocyte-macrophage subset proportions. While classical 
      monocyte-macrophages were predominant in the Wistar, there were relatively more 
      of the non-classical subset in the SHR, which have been implicated in 
      pro-inflammatory roles in a number of diseases. When bone marrow-derived 
      macrophages (BMDMs) were co-cultured with stellate neurons, they made Wistar 
      neurons recapitulate the SHR nicotinic stimulated calcium transient. Wistar BMDMs 
      however, had no effect on SHR neurons, even though SHR BMDMs increased SHR neuron 
      responsiveness further above their hyper-responsive state. Taken together, these 
      findings show that macrophages can be potent enhancers of sympathetic neuronal 
      calcium responsiveness, and thus could conceivably play a role in peripheral 
      sympathetic hyperactivity observed in the early stages of hypertension.
CI  - Copyright (c) 2022 Neely, Domingos and Paterson.
FAU - Neely, Oliver C
AU  - Neely OC
AD  - Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, 
      United Kingdom.
FAU - Domingos, Ana I
AU  - Domingos AI
AD  - Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, 
      United Kingdom.
FAU - Paterson, David J
AU  - Paterson DJ
AD  - Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, 
      United Kingdom.
LA  - eng
GR  - RG/17/14/33085/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
DEP - 20220127
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC8828732
OTO - NOTNLM
OT  - SHR
OT  - calcium imaging
OT  - dysautonomia
OT  - flow cytometry
OT  - hypertension
OT  - macrophages
OT  - stellate neurons
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/02/15 06:00
MHDA- 2022/02/15 06:01
PMCR- 2021/01/01
CRDT- 2022/02/14 05:35
PHST- 2021/11/02 00:00 [received]
PHST- 2021/12/21 00:00 [accepted]
PHST- 2022/02/14 05:35 [entrez]
PHST- 2022/02/15 06:00 [pubmed]
PHST- 2022/02/15 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2021.807904 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Jan 27;8:807904. doi: 10.3389/fcvm.2021.807904. 
      eCollection 2021.