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Rosuvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4

BAO Xiao-mei1, ZHENG Hong-chao1, WU Chun-fang2, LU Guo-ping2   

  1. 1.Department of Cardiology, Xuhui District Central Hospital, Shanghai 200031, China; 2.Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2013-11-28 Published:2013-12-03
  • Supported by:

    Natural Science Foundation of Shanghai,12ZR1429100

Abstract:

Objective To study inhibition of rosuvastatin (Rosu) on homocysteine (Hcy)-induced reactive oxygen species (ROS) and apoptosis in endothelial progenitor cells (EPCs). Methods EPCs were isolated from peripheral blood and then incubated with Hcy, or pre-incubated with Rosu or with different stress signaling pathway inhibitors including mevalonate (100 μmol/L), acetyl-cysteine (NAC, 10 μmol/L), NADPH oxidase inhibitor (DPI, 10 μmol/L), and endothelial nitric oxide synthase inhibitor (LNMA, 1 mmol/L) before adding Hcy. Apoptosis rate was evaluated by fluorescence activated cell sorting (FACS) analysis. ROS levels were detected by 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFH-DA). NADPH oxidases were evaluated with lucigenin-enhanced chemiluminescence. Expression of Nox4 mRNA was measured by RT-PCR. Results Rosu remarkably inhibited Hcy-induced ROS accumulation and apoptosis of EPCs, and antagonized Hcy-induced activation of NADPH oxidase and Nox4 mRNA expression. Nox4 siRNA transfected EPCs with a similar effect. Conclusion The protective effect of Rosu on EPCs possibly involves inhibition of Hcy-induced activation of Nox, ROS accumulation, and apoptosis of EPCs through Nox4 dependent mechanisms.

Key words: rosuvastatin, homocysteine, apoptosis, reactive oxygen species, Nox4