Skip to main content
Log in

Human endothelial progenitor cells isolated from COPD patients are dysfunctional

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). More than 44% of these patients present with generalized atherosclerosis at autopsy. It is accepted that endothelial progenitor cells (EPCs) participate in the repair of dysfunctional endothelium and thus protects against atherosclerosis. However, whether COPD affects the repairing capacity of EPCs is unknown. Therefore, the objective of this study was to determine whether and how EPCs are involved in the vascular repair process in patients with COPD. In our study, EPCs from 25 COPD and 16 control patients were isolated by Ficoll density-gradient centrifugation and identified using fluorescence activated cell sorting. Transwell Migratory Assay was performed to determine the number of EPC colony-forming units and the adherent capacity late-EPCs to human umbilical vein endothelial cells. Following arterial damage in NOD/SCID mice, the number of EPCs incorporated at the injured vascular site was determined using a fluorescence microscope. We found that the number of EPC clusters and cell migration, as well as the expression of CXCR4, was significantly decreased in patients with COPD. Additionally, the number of late-EPCs adherent to HUVEC tubules was significantly reduced, and fewer VEGFR2+-staining cells were incorporated into the injured site in COPD patients. Our study demonstrates that EPC capacity of repair was affected in COPD patients, which may contribute to altered vascular endothelium in this patient population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Finkelstein J, Cha E, Scharf SM (2009) Chronic obstructive pulmonary disease as an independent risk factor for cardiovascular morbidity. Int J Chron Obstruct Pulmon Dis 4:337–349

    PubMed  Google Scholar 

  2. Mannino DM, Brown C, Giovino GA (1997) Obstructive lung disease deaths in the United States from 1979 through 1993. An analysis using multiple-cause mortality data. Am J Respir Crit Care Med 156(3 Pt 1):814–818

    PubMed  CAS  Google Scholar 

  3. Zvezdin B et al (2009) A postmortem analysis of major causes of early death in patients hospitalized with COPD exacerbation. Chest 136(2):376–380

    Article  PubMed  Google Scholar 

  4. Macnee W, Maclay J, McAllister D (2008) Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc 5(8):824–833

    Article  PubMed  CAS  Google Scholar 

  5. Eickhoff P et al (2008) Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 178(12):1211–1218

    Article  PubMed  CAS  Google Scholar 

  6. Barbera JA, Peinado VI, Santos S (2003) Pulmonary hypertension in chronic obstructive pulmonary disease. Eur Respir J 21(5):892–905

    Article  PubMed  CAS  Google Scholar 

  7. Chung KF, Adcock IM (2008) Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 31(6):1334–1356

    Article  PubMed  CAS  Google Scholar 

  8. Peichev M et al (2000) Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95(3):952–958

    PubMed  CAS  Google Scholar 

  9. Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95(4):343–353

    Article  PubMed  CAS  Google Scholar 

  10. Zampetaki A, Kirton J, Xu Q (2008) Vascular repair by endothelial progenitor cells. Cardiovasc Res 78(3):413–421

    Article  PubMed  CAS  Google Scholar 

  11. Peinado VI et al (2006) Identification of vascular progenitor cells in pulmonary arteries of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 34(3):257–263

    Article  PubMed  CAS  Google Scholar 

  12. Giannotti G, Landmesser U (2007) Endothelial dysfunction as an early sign of atherosclerosis. Herz 32(7):568–572

    Article  PubMed  Google Scholar 

  13. Aguila HL (2006) Regulation of hematopoietic niches by sympathetic innervation. Bioessays 28(7):687–691

    Article  PubMed  CAS  Google Scholar 

  14. Katayama Y et al (2006) Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124(2):407–421

    Article  PubMed  CAS  Google Scholar 

  15. Tepper OM et al (2002) Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106(22):2781–2786

    Article  PubMed  Google Scholar 

  16. Toshner M et al (2009) Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension. Am J Respir Crit Care Med 180(8):780–787

    Article  PubMed  Google Scholar 

  17. Mukai N et al (2008) A comparison of the tube forming potentials of early and late endothelial progenitor cells. Exp Cell Res 314(3):430–440

    Article  PubMed  CAS  Google Scholar 

  18. Tressel SL et al (2007) Laminar shear inhibits tubule formation and migration of endothelial cells by an angiopoietin-2 dependent mechanism. Arterioscler Thromb Vasc Biol 27(10):2150–2156

    Article  PubMed  CAS  Google Scholar 

  19. Zocchi MR, Poggi A (2004) PECAM-1, apoptosis and CD34+ precursors. Leuk Lymphoma 45(11):2205–2213

    Article  PubMed  CAS  Google Scholar 

  20. Hibbert B et al (2009) Inhibition of endothelial progenitor cell glycogen synthase kinase-3beta results in attenuated neointima formation and enhanced re-endothelialization after arterial injury. Cardiovasc Res 83(1):16–23

    Article  PubMed  CAS  Google Scholar 

  21. Sermsathanasawadi N et al (2009) Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro. J Radiat Res (Tokyo) 50(5):469–475

    Article  CAS  Google Scholar 

  22. Heida NM et al (2010) Effects of obesity and weight loss on the functional properties of early outgrowth endothelial progenitor cells. J Am Coll Cardiol 55(4):357–367

    Article  PubMed  CAS  Google Scholar 

  23. Carbajal KS et al (2010) Migration of engrafted neural stem cells is mediated by CXCL12 signaling through CXCR4 in a viral model of multiple sclerosis. Proc Natl Acad Sci USA 107(24):11068–11073

    Article  PubMed  CAS  Google Scholar 

  24. Petit I, Jin D, Rafii S (2007) The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol 28(7):299–307

    Article  PubMed  CAS  Google Scholar 

  25. Takahashi T et al (2011) Impaired endothelial progenitor cell mobilization and colony-forming capacity in chronic obstructive pulmonary disease. Respirology 16(4):680–687

    Article  PubMed  Google Scholar 

  26. Stellos K et al (2008) Platelet-derived stromal cell-derived factor-1 regulates adhesion and promotes differentiation of human CD34+ cells to endothelial progenitor cells. Circulation 117(2):206–215

    Article  PubMed  CAS  Google Scholar 

  27. Newman PJ, Newman DK (2003) Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology. Arterioscler Thromb Vasc Biol 23(6):953–964

    Article  PubMed  CAS  Google Scholar 

  28. Hirata Y et al (2010) Diagnosis and treatment of endothelial dysfunction in cardiovascular disease. Int Heart J 51(1):1–6

    Article  PubMed  CAS  Google Scholar 

  29. Pan S (2009) Molecular mechanisms responsible for the atheroprotective effects of laminar shear stress. Antioxid Redox Signal 11(7):1669–1682

    Article  PubMed  CAS  Google Scholar 

  30. Hamed S, Roguin A (2006) Endothelial progenitor cells and atherosclerosis. Harefuah 145(5):358–361, 397

    Google Scholar 

  31. Sitia S et al (2010) From endothelial dysfunction to atherosclerosis. Autoimmun Rev 9(12):830–834

    Article  PubMed  CAS  Google Scholar 

  32. Hill JM et al (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348(7):593–600

    Article  PubMed  Google Scholar 

  33. Gehling UM et al (2000) In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 95(10):3106–3112

    PubMed  CAS  Google Scholar 

  34. Sandstedt J et al (2010) C-kit+ CD45− cells found in the adult human heart represent a population of endothelial progenitor cells. Basic Res Cardiol 105(4):545–556

    Article  PubMed  Google Scholar 

  35. Zhang Y et al (2009) Release of proinflammatory mediators and expression of proinflammatory adhesion molecules by endothelial progenitor cells. Am J Physiol Heart Circ Physiol 296(5):H1675–H1682

    Article  PubMed  CAS  Google Scholar 

  36. Thill M et al (2008) Late outgrowth endothelial progenitor cells in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci 49(6):2696–2708

    Article  PubMed  Google Scholar 

  37. Timmermans F et al (2007) Endothelial outgrowth cells are not derived from CD133+ cells or CD45+ hematopoietic precursors. Arterioscler Thromb Vasc Biol 27(7):1572–1579

    Article  PubMed  CAS  Google Scholar 

  38. Sata M et al (2000) A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia. J Mol Cell Cardiol 32(11):2097–2104

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Lihua Liu for technical assistance, and Dr. Weiping Tan, Dr. Shuxiang Zhang and the staff of nurses in respiratory department of the First Affiliated Hospital of Sun Yat-sen University for collecting clinical cases, and Prof Zhengyu Dong for the preparation of the manuscript and cover letter.

Conflict of Interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Canmao Xie.

Additional information

Xiaoran Liu and Canmao Xie authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, X., Xie, C. Human endothelial progenitor cells isolated from COPD patients are dysfunctional. Mol Cell Biochem 363, 53–63 (2012). https://doi.org/10.1007/s11010-011-1157-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-1157-y

Keywords

Navigation