Remnant-like particles accelerate endothelial progenitor cells senescence and induce cellular dysfunction via an oxidative mechanism

• Published in: Atherosclerosis 2009-02, Vol.202 (2), p.405-414
• Main Authors: Liu, Ling, Wen, Tie, Zheng, Xiao-yan, Yang, De-Guang, Zhao, Shui-Ping, Xu, Dan-Yan, Lü, Guo-hua
• Format: Article
• Language: English
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cardiovascular; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Division - drug effects; Cell Division - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cellular Senescence - drug effects; Cellular Senescence - physiology; Cholesterol - pharmacology; Endothelial dysfunction; Endothelial progenitor cell; Endothelium, Vascular - cytology; Fundamental and applied biological sciences. Psychology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Humans; Lipoproteins - pharmacology; Medical sciences; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Peroxynitrous Acid - metabolism; Remnant-like particles; Senescence; Superoxide Dismutase - metabolism; Triglycerides - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2008.05.024

Abstract Remnant-like particles (RLPs) are closely associated with coronary heart disease and can induce endothelial dysfunction through oxidative mechanisms. Many risk factors accelerate the onset of endothelial progenitor cells (EPCs) senescence via increased oxidative stress. In this study, we investigated the effect of RLPs on EPCs senescence and function. RLPs were isolated from postprandial plasma of hypertriglyceridemic patients by use of the immunoaffinity gel mixture of anti-apoA-1 and anti-apoB-100 monoclonal antibodies. Our results show that EPCs became senescent as determined by senescence-associated acidic β-galactosidase (SA-β-Gal) staining after ex vivo cultivation without any stimulation. Co-incubation with RLPs accelerated the increase in SA-β-Gal-positive EPCs. The acceleration of RLPs-induced EPCs senescence occurred dose-dependently with a maximal effect when EPCs were treated with RLPs at 0.10 mg cholesterol/mL ( P < 0.01). Moreover, RLPs decreased adhesion, migration and proliferation capacities of EPCs as assessed by adherence to fibronectin, modified Boyden chamber technique and MTT assay ( P < 0.01), respectively. RLPs increased nitrotyrosine staining in EPCs. However, RLPs-induced EPCs senescence and dysfunction were significantly inhibited by pre-treatment of superoxide dismutase (50 U/mL) ( P < 0.05). Our results provide evidence that RLPs accelerate the onset of EPC senescence via increased oxidative stress, accompanying with the impairment of adhesion, migration and proliferation capacities.