title: High density lipoprotein protects mesenchymal stem cells from oxidative stress-induced apoptosis via activation of the PI3K/Akt pathway and suppression of reactive oxygen species.
abstract: The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H(2)O(2)) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H(2)O(2)-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS.
authors: Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China. qian.juying@zs-hospital.sh.cn.
authors: Jianfeng
authors: J
authors: Xu
authors: Juying
authors: J
authors: Qian
authors: Xinxing
authors: X
authors: Xie
authors: Li
authors: L
authors: Lin
authors: Yunzeng
authors: Y
authors: Zou
authors: Mingqiang
authors: M
authors: Fu
authors: Zheyong
authors: Z
authors: Huang
authors: Guoping
authors: G
authors: Zhang
authors: Yangang
authors: Y
authors: Su
authors: Junbo
authors: J
authors: Ge
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008075:Lipoproteins, HDL; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt