N-acetylcysteine differentially regulates the populations of bone marrow and circulating endothelial progenitor cells in mice with limb ischemia.

Abstract

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.

• Authors: Yuqi Cui, Lingjuan Liu, Yuan Xiao, Xin Li, Jia Zhang, Xiaoyun Xie, Jie Tian, Chandan K Sen, Xiaoming He, Hong Hao, Zhenguo Liu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 881 Pg. 173233 (Aug 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 32492379 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Angiogenesis Inducing Agents
• Antioxidants
• Reactive Oxygen Species
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Angiogenesis Inducing Agents (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Bone Marrow Cells (drug effects, metabolism, pathology)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Endothelial Progenitor Cells (drug effects, metabolism, pathology)
• Hindlimb
• Ischemia (drug therapy, metabolism, pathology, physiopathology)
• Male
• Mice, Inbred C57BL
• Muscle, Skeletal (blood supply)
• Neovascularization, Physiologic (drug effects)
• Oxidative Stress (drug effects)
• Phenotype
• Reactive Oxygen Species (metabolism)
• Recovery of Function