Treg cells depletion is a mechanism that drives microvascular dysfunction in mice with established hypertension.
Animals
Arterial Pressure
Biomarkers
/ metabolism
Hypertension
/ immunology
Lymphocyte Count
Lymphocyte Depletion
Mice, Inbred C57BL
Microvessels
/ physiopathology
Models, Biological
NADPH Oxidases
/ metabolism
Oxidative Stress
Phosphorylation
Systole
T-Lymphocytes, Regulatory
/ immunology
Vascular Resistance
Autophagy
Endoplasmic reticulum stress
Established hypertension
Oxidative stress and resistance artery
Treg cells
Journal
Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Titre abrégé: Biochim Biophys Acta Mol Basis Dis
Pays: Netherlands
ID NLM: 101731730
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
16
05
2018
revised:
10
10
2018
accepted:
26
10
2018
pubmed:
12
11
2018
medline:
19
9
2019
entrez:
12
11
2018
Statut:
ppublish
Résumé
Microvascular dysfunction is a major complication in hypertensive patients. We previously reported that CD4 Here we showed that Treg cells from mice model of established hypertension displayed an enhanced apoptotic rate, which was rescued with Treg cells transfer and autophagy inhibition. We also showed increased autophagy in mesenteric resistance artery (MRA) in mice with established hypertension. Importantly, the inhibition of autophagy or one single transfer of Treg cells into mice with established hypertension improved the microvascular function independently of high blood pressure. The protection involves the modulation of interleukin-10 (IL-10), inflammation, endoplasmic reticulum (ER) stress, oxidative stress, Akt, and eNOS. The present study suggests that Treg cells survival is regulated by autophagy. Also, Treg cells as a cellular therapy aimed at rescuing the microvascular function through an autophagy-dependent mechanism and independently of arterial blood pressure lowering effects. Because our mouse model of established hypertension mimics the clinical situation, our results have the potential for new therapeutic approaches that involve the manipulation of Treg cells and autophagy to overcome established hypertension-induced cardiovascular complications.
Sections du résumé
BACKGROUND
Microvascular dysfunction is a major complication in hypertensive patients. We previously reported that CD4
METHODS & RESULTS
Here we showed that Treg cells from mice model of established hypertension displayed an enhanced apoptotic rate, which was rescued with Treg cells transfer and autophagy inhibition. We also showed increased autophagy in mesenteric resistance artery (MRA) in mice with established hypertension. Importantly, the inhibition of autophagy or one single transfer of Treg cells into mice with established hypertension improved the microvascular function independently of high blood pressure. The protection involves the modulation of interleukin-10 (IL-10), inflammation, endoplasmic reticulum (ER) stress, oxidative stress, Akt, and eNOS.
CONCLUSIONS
The present study suggests that Treg cells survival is regulated by autophagy. Also, Treg cells as a cellular therapy aimed at rescuing the microvascular function through an autophagy-dependent mechanism and independently of arterial blood pressure lowering effects. Because our mouse model of established hypertension mimics the clinical situation, our results have the potential for new therapeutic approaches that involve the manipulation of Treg cells and autophagy to overcome established hypertension-induced cardiovascular complications.
Identifiants
pubmed: 30414897
pii: S0925-4439(18)30434-4
doi: 10.1016/j.bbadis.2018.10.031
pii:
doi:
Substances chimiques
Biomarkers
0
NADPH Oxidases
EC 1.6.3.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
403-412Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL095566
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.