Rosuvastatin Enhances Angiogenesis via eNOS-Dependent Mobilization of Endothelial Progenitor Cells

Junlan Zhou, Min Cheng, Yu Hua Liao, Yu Hu, Min Wu, Qing Wang, Bo Qin, Hong Wang, Yan Zhu, Xiu Mei Gao, David Goukassian, Ting C. Zhao, Yao Liang Tang, Raj Kishore, Gangjian Qin

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32 Scopus citations

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.

Original languageEnglish (US)
Article numbere63126
JournalPloS one
Volume8
Issue number5
DOIs
StatePublished - May 21 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Zhou, J., Cheng, M., Liao, Y. H., Hu, Y., Wu, M., Wang, Q., Qin, B., Wang, H., Zhu, Y., Gao, X. M., Goukassian, D., Zhao, T. C., Tang, Y. L., Kishore, R., & Qin, G. (2013). Rosuvastatin Enhances Angiogenesis via eNOS-Dependent Mobilization of Endothelial Progenitor Cells. PloS one, 8(5), [e63126]. https://doi.org/10.1371/journal.pone.0063126