on August 19, 2004
Published online before print August 19, 2004, doi: 10.1161/01.ATV.0000142810.27849.8f
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 2, 2004
Accepted on July 26, 2004
Human Endothelial Progenitor Cells Tolerate Oxidative Stress Caused by Intrinsically High Expression of Manganese Superoxide Dismutase
Tongrong He ;
From the Departments of Anesthesiology (T.H., T.E.P., Z.S.K.), Molecular Pharmacology and Experimental Therapeutics (A.T., Z.S.K.), and Internal Medicine (E.L.H., A.T., N.M.C.), Division of Cardiovascular Disease, Mayo Clinic College of Medicine, Rochester, Minn; and the Free Radical and Radiation Biology Program (L.W.O.), Department of Radiation Oncology, The University of Iowa, Iowa City.
* To whom correspondence should be addressed. E-mail: katusic.zvonimir{at}mayo.edu.
Objective--Endothelial progenitor cells (EPCs) display a unique aptitude to promote angiogenesis and restore endothelial function of injured vessels. How progenitor cells can execute a regenerative program in the unfavorable environment of injury/inflammation-induced oxidative stress is poorly understood. We hypothesized that EPCs are resistant to oxidative stress and that this resistance is caused by high expression and activity of antioxidant enzymes.
Methods and Results--EPCs outgrown from human blood of healthy subjects demonstrated a marked resistance to cytotoxic effect of LY83583 (a O2-• generator), tumor necrosis factor-
, and serum depletion. LY83583 inhibited in vitro tube formation by human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (CAECs), but not by EPCs. Compared with HUVECs and CAECs, EPCs exhibited 
3- to 4-fold higher expression and activity of manganese superoxide dismutase (MnSOD), but not CuZnSOD or catalase. The antioxidant profile in EPCs was associated with preservation of the mitochondrial network when exposed to LY83583. Moreover, cytotoxic effects of LY83583 on CAECs and HUVECs were reversed by adenoviral overexpression of MnSOD.
Conclusions--Human EPCs are resistant to oxidative stress. High intrinsic expression of MnSOD is a critical mechanism protecting EPCs against oxidative stress.
Key words: endothelium • antioxidants • angiogenesis • superoxide • nitric oxide synthase • endothelial progenitor cells
Related Article:
- Endothelial Progenitor Cells at Work: Not Mature Yet, but Already Stress-Resistant
- Lothar Rössig, Carmen Urbich, and Stefanie Dimmeler
Arterioscler Thromb Vasc Biol 2004 24: 1977-1979.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  M. Thurau, G. Marquardt, N. Gonin-Laurent, K. Weinlander, E. Naschberger, R. Jochmann, K. R. Alkharsah, T. F. Schulz, M. Thome, F. Neipel, et al. Viral Inhibitor of Apoptosis vFLIP/K13 Protects Endothelial Cells against Superoxide-Induced Cell Death J. Virol., January 15, 2009; 83(2): 598 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Urish, J. B. Vella, M. Okada, B. M. Deasy, K. Tobita, B. B. Keller, B. Cao, J. D. Piganelli, and J. Huard Antioxidant Levels Represent a Major Determinant in the Regenerative Capacity of Muscle Stem Cells Mol. Biol. Cell, January 1, 2009; 20(1): 509 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. He, T. Lu, L. V. d'Uscio, C.-F. Lam, H.-C. Lee, and Z. S. Katusic Angiogenic Function of Prostacyclin Biosynthesis in Human Endothelial Progenitor Cells Circ. Res., July 3, 2008; 103(1): 80 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dimmeler and A. Leri Aging and Disease as Modifiers of Efficacy of Cell Therapy Circ. Res., June 6, 2008; 102(11): 1319 - 1330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Spinetti, N. Kraenkel, C. Emanueli, and P. Madeddu Diabetes and vessel wall remodelling: from mechanistic insights to regenerative therapies Cardiovasc Res, May 1, 2008; 78(2): 265 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Levonen, E. Vahakangas, J. K. Koponen, and S. Yla-Herttuala Antioxidant Gene Therapy for Cardiovascular Disease: Current Status and Future Perspectives Circulation, April 22, 2008; 117(16): 2142 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dulak, J. Deshane, A. Jozkowicz, and A. Agarwal Heme Oxygenase-1 and Carbon Monoxide in Vascular Pathobiology: Focus on Angiogenesis Circulation, January 15, 2008; 117(2): 231 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Sorrentino, F. H. Bahlmann, C. Besler, M. Muller, S. Schulz, N. Kirchhoff, C. Doerries, T. Horvath, A. Limbourg, F. Limbourg, et al. Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus: Restoration by the Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Rosiglitazone Circulation, July 10, 2007; 116(2): 163 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Kissel, R. Lehmann, B. Assmus, A. Aicher, J. Honold, U. Fischer-Rasokat, C. Heeschen, I. Spyridopoulos, S. Dimmeler, and A. M. Zeiher Selective Functional Exhaustion of Hematopoietic Progenitor Cells in the Bone Marrow of Patients With Postinfarction Heart Failure J. Am. Coll. Cardiol., June 19, 2007; 49(24): 2341 - 2349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Chen, S.-J. Lin, F.-Y. Lin, T.-C. Wu, C.-R. Tsao, P.-H. Huang, P.-L. Liu, Y.-L. Chen, and J.-W. Chen High Glucose Impairs Early and Late Endothelial Progenitor Cells by Modifying Nitric Oxide-Related but Not Oxidative Stress-Mediated Mechanisms Diabetes, June 1, 2007; 56(6): 1559 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kubo, T.-S. Li, R. Suzuki, M. Ohshima, S.-L. Qin, and K. Hamano Short-term pretreatment with low-dose hydrogen peroxide enhances the efficacy of bone marrow cells for therapeutic angiogenesis Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2582 - H2588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Lamping Endothelial Progenitor Cells: Sowing the Seeds for Vascular Repair Circ. Res., May 11, 2007; 100(9): 1243 - 1245. [Full Text] [PDF]
|
|
|
|
|
|
A. V. R. Santhanam, L. A. Smith, T. He, K. A. Nath, and Z. S. Katusic Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2 Circ. Res., May 11, 2007; 100(9): 1379 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Lu, T. He, Z. S. Katusic, and H.-C. Lee Molecular Mechanisms Mediating Inhibition of Human Large Conductance Ca2+-Activated K+ Channels by High Glucose Circ. Res., September 15, 2006; 99(6): 607 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Haendeler and S. Dimmeler Inseparably Tied: Functional and Antioxidative Capacity of Endothelial Progenitor Cells Circ. Res., February 3, 2006; 98(2): 157 - 158. [Full Text] [PDF]
|
|
|
|
|
|
G. Galasso, S. Schiekofer, K. Sato, R. Shibata, D. E. Handy, N. Ouchi, J. A. Leopold, J. Loscalzo, and K. Walsh Impaired Angiogenesis in Glutathione Peroxidase-1-Deficient Mice Is Associated With Endothelial Progenitor Cell Dysfunction Circ. Res., February 3, 2006; 98(2): 254 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Smadja, I. Bieche, G. Uzan, H. Bompais, L. Muller, C. Boisson-Vidal, M. Vidaud, M. Aiach, and P. Gaussem PAR-1 Activation on Human Late Endothelial Progenitor Cells Enhances Angiogenesis In Vitro With Upregulation of the SDF-1/CXCR4 System Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2321 - 2327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Yoon, J. Hur, K.-W. Park, J.-H. Kim, C.-S. Lee, I.-Y. Oh, T.-Y. Kim, H.-J. Cho, H.-J. Kang, I.-H. Chae, et al. Synergistic Neovascularization by Mixed Transplantation of Early Endothelial Progenitor Cells and Late Outgrowth Endothelial Cells: The Role of Angiogenic Cytokines and Matrix Metalloproteinases Circulation, September 13, 2005; 112(11): 1618 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. He, T. E. Peterson, and Z. S. Katusic Paracrine mitogenic effect of human endothelial progenitor cells: role of interleukin-8 Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H968 - H972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rossig, C. Urbich, and S. Dimmeler Endothelial Progenitor Cells at Work: Not Mature Yet, but Already Stress-Resistant Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1977 - 1979. [Full Text] [PDF]
|
|