, 14:267 | Cite as

Cyclic GMP protects endothelial progenitors from oxidative stress

  • Anna Maria CuratolaEmail author
  • Jie Xu
  • Karen D. Hendricks-Munoz
Original Paper


Endothelial progenitor cells (EPCs) play a critical role in the repair of damaged blood vessels and/or in the growth of new ones in ischemic tissues. Elevated levels of oxygen radicals, which accumulate in the ischemic tissue, could compromise the angiogenic potential of EPCs. To determine if oxidative stress alters the angiogenic response of EPCs and to identify possible cellular targets that protect EPCs from the damaging effects of oxidative stress, we have investigated vascular development in embryonic bodies (EBs) under hyperoxic conditions. Murine EBs at differentiaton day 2 were cultured for 3 days under normoxic (21% O2) or hyperoxic (60% O2) conditions. Hyperoxic EBs showed a moderate reduction in Pecam-1, Vegfr-2, eNOS and Tie2 mRNA levels compared to normoxic EBs. However, immunostaining of hyperoxic EBs with antibodies against PECAM-1 after 1 week recovery at room air revealed a defective vasculature completely deficient in branches, while normoxic EBs developed a normal vascular plexus. Oxygen-induced defective vascular development correlated with a dramatic decrease in soluble guanylyl cyclase, phosphodiesterase (Pde) 4B and Pde4C mRNAs. Oxidative stress did not affect the expression of adenylyl cyclase 6 and Pde5. The abnormal vascular development caused by hyperoxia was reverted by pharmacological treatments that increased cGMP levels, such as 8-bromo-cGMP or 4-{[3′,4′-(methylenedioxy)benzyl]amino}-6-methoxyquinazoline, a specific inhibitor of PDE5. These results indicated that oxidative stress inhibits vascular development from EPCs through its effects on levels of cyclic nucleotides and suggested that therapies that target cyclic nucleotide turnover may be useful in protecting vascular repair under oxidative conditions.


Oxidative stress Endothelial progenitor cell Vascular development Cyclic nucleotide Cyclase Phosphodiesterase 



This work was supported in part by a donation from the Jack Cary Eichenbaum Foundation. We thank Marian Acevedo, Andrea Zambetti, and Jenifer Lee for their technical help. We thank Dr. David Moscatelli for critical reading of the manuscript. We also thank Dr. Frederick Naftolin for making the EVOS Digital Fluorescence Microscope available to us.

Conflict of interest


Supplementary material

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Supplementary material 1 (PDF 1650 kb)
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Supplementary material 3 (PDF 3471 kb)
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Supplementary material 4 (PDF 348 kb)
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Supplementary material 5 (PDF 4145 kb)


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Anna Maria Curatola
    • 1
    Email author
  • Jie Xu
    • 1
  • Karen D. Hendricks-Munoz
    • 1
  1. 1.Division of Neonatology, Department of PediatricsNew York University School of MedicineNew YorkUSA

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