N-acetylcysteine differentially regulates the populations of bone marrow and circulating endothelial progenitor cells in mice with limb ischemia.
Acetylcysteine
/ pharmacology
Angiogenesis Inducing Agents
/ pharmacology
Animals
Antioxidants
/ pharmacology
Apoptosis
/ drug effects
Bone Marrow Cells
/ drug effects
Cell Proliferation
/ drug effects
Disease Models, Animal
Endothelial Progenitor Cells
/ drug effects
Hindlimb
Ischemia
/ drug therapy
Male
Mice, Inbred C57BL
Muscle, Skeletal
/ blood supply
Neovascularization, Physiologic
/ drug effects
Oxidative Stress
/ drug effects
Phenotype
Reactive Oxygen Species
/ metabolism
Recovery of Function
Angiogenesis
EPCs
Limb ischemia
NAC
Journal
European journal of pharmacology
ISSN: 1879-0712
Titre abrégé: Eur J Pharmacol
Pays: Netherlands
ID NLM: 1254354
Informations de publication
Date de publication:
15 Aug 2020
15 Aug 2020
Historique:
received:
28
09
2019
revised:
21
05
2020
accepted:
29
05
2020
pubmed:
4
6
2020
medline:
11
5
2021
entrez:
4
6
2020
Statut:
ppublish
Résumé
Endothelial progenitor cells (EPCs) are important to tissue repair and regeneration especially after ischemic injury, and very heterogeneous in phenotypes and biological features. Reactive oxygen species are involved in regulating EPC number and function. N-acetylcysteine (NAC) inhibits ischemia-induced reactive oxygen species formation and promotes ischemic limb recovery. This study was to evaluate the effect of NAC on EPC subpopulations in bone marrow (BM) and blood in mice with limb ischemia. Limb ischemia was induced by femoral artery ligation in male C57BL/6 mice with or without NAC treatment. EPC subpopulations, intracellular reactive oxygen species production, cell proliferation and apoptosis in BM and blood cells were analyzed at baseline, day 3 (acute ischemia) and 21 (chronic) after ligation. c-Kit+/CD31+, Sca-1+/Flk-1+, CD34+/CD133+, and CD34+/Flk-1+ were used to define EPC subpopulations. Limb blood flow, function, muscle structure, and capillary density were evaluated with laser Doppler perfusion imaging, treadmill test, and immunohistochemistry, respectively, at day 3, 7, 14 and 21 post ischemia. Reactive oxygen species production in circulating and BM mononuclear cells and EPCs populations were significantly increased in BM and blood in mice with acute and chronic ischemia. NAC treatment effectively blocked ischemia-induced reactive oxygen species production in circulating and BM mononuclear cells, and selectively increased EPC population in circulation, not BM, with preserved proliferation in mice with chronic ischemia, and enhanced limb blood flow and function recovery, while preventing acute ischemia-induced increase in BM and circulating EPCs. These data demonstrated that NAC selectively enhanced circulating EPC population in mice with chronic limb ischemia.
Identifiants
pubmed: 32492379
pii: S0014-2999(20)30325-3
doi: 10.1016/j.ejphar.2020.173233
pmc: PMC7483875
mid: NIHMS1605381
pii:
doi:
Substances chimiques
Angiogenesis Inducing Agents
0
Antioxidants
0
Reactive Oxygen Species
0
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
173233Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES026200
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL124122
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148196
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
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