1. Rosuvastatin Enhances Angiogenesis via eNOS-Dependent Mobilization of Endothelial Progenitor Cells
- Author
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Ting C. Zhao, Hong Wang, Min Wu, David A. Goukassian, Raj Kishore, Yan Zhu, Yao Liang Tang, Bo Qin, Yu Hua Liao, Qing Wang, Xiumei Gao, Gangjian Qin, Junlan Zhou, Yu Hu, and Min Cheng
- Subjects
Male ,Angiogenesis ,Myocardial Infarction ,lcsh:Medicine ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Pharmacology ,Cardiovascular ,Neovascularization ,Mice ,0302 clinical medicine ,Enos ,Bone Marrow ,Cell Movement ,Ischemia ,Molecular Cell Biology ,Bone Marrow and Stem Cell Transplantation ,Rosuvastatin Calcium ,lcsh:Science ,Peripheral Vascular Diseases ,Sulfonamides ,Multidisciplinary ,biology ,Chemistry ,Stem Cells ,Cell Differentiation ,Hematology ,Hindlimb ,Adult Stem Cells ,Medicine ,medicine.symptom ,Cellular Types ,Research Article ,Signal Transduction ,Hematopoietic Progenitor Cells ,Nitric Oxide Synthase Type III ,Cell Potency ,Neovascularization, Physiologic ,Bone Marrow Cells ,Phosphoinositide Signal Transduction ,Signaling Pathways ,03 medical and health sciences ,Vasculogenesis ,Vascular Biology ,medicine ,Animals ,Cell Lineage ,Progenitor cell ,Biology ,Matrigel ,lcsh:R ,Endothelial Cells ,medicine.disease ,biology.organism_classification ,Hematopoietic Stem Cells ,Transplantation ,Fluorobenzenes ,Mice, Inbred C57BL ,Pyrimidines ,Regional Blood Flow ,Immunology ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
Circulating endothelial progenitor cells (circEPCs) of bone marrow (BM) origin contribute to postnatal neovascularization and represent a potential therapeutic target for ischemic disease. Statins are beneficial for ischemia disease and have been implicated to increase neovascularization via mechanisms independent of lipid lowering. However, the effect of Statins on EPC function is not completely understood. Here we sought to investigate the effects of Rosuvastatin (Ros) on EPC mobilization and EPC-mediated neovascularization during ischemic injury. In a mouse model of surgically-induced hindlimb ischemia (HLI), treatment of mice with low dose (0.1 mg/kg) but not high dose (5 mg/kg) significantly increased capillary density and accelerated blood flow recovery, as compared to saline-treated group. When HLI was induced in mice that had received Tie2/LacZ BM transplantation, Ros treatment led a significantly larger amount of endothelial cells (ECs) of BM origin incorporated at ischemic sites than saline. After treatment of mice with a single low dose of Ros, circEPCs significantly increased from 2 h, peaked at 4 h, declined until 8 h. In a growth-factor reduced Matrigel plug-in assay, Ros treatment for 5 d induced endothelial lineage differentiation in vivo. Interestingly, the enhanced circEPCs and post-HLI neovascularization stimulated by Ros were blunted in mice deficient in endothelial nitric oxide synthase (eNOS), and Ros increased p-Akt/p-eNOS levels in EPCs in vitro, indicating these effects of Ros are dependent on eNOS activity. We conclude that Ros increases circEPCs and promotes their de novo differentiation through eNOS pathway.
- Published
- 2013