Basic Research in Cardiology

, 102:565 | Cite as

Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease

  • Nikos Werner
  • Sven Wassmann
  • Patrick Ahlers
  • Tobias Schiegl
  • Sonja Kosiol
  • Andreas Link
  • Katrin Walenta
  • Georg Nickenig
ORIGINAL CONTRIBUTION

Abstract

Endothelial progenitor cells (EPC) predict morbidity and mortality in patients at cardiovascular risk.Patients with low EPC counts and impaired endothelial colony forming activity have a higher incidence for cardiovascular events compared to patients with high EPC counts and favorable colony forming activity. The pathophysiological basis for this finding may be an insufficient endothelial cell repair by EPC.We postulate that EPC influence coronary endothelial function which itself is relevant for the outcome of patients at cardiovascular risk. To test this hypothesis in humans, endothelial function was invasively assessed in 90 patients with coronary heart disease by quantitative coronary angiography during intracoronary acetylcholine infusion. Flow cytometry of mononuclear cells isolated from peripheral blood was performed to assess CD133+ or CD34+/KDR+ EPC. EPC function was assessed ex vivo by determination of endothelial colony forming units. Low EPC number as well as impaired endothelial colony forming activity correlated with severely impaired coronary endothelial function in univariate analysis. Multivariate analysis revealed that only the number of EPC predicts severe endothelial dysfunction independent of classical cardiovascular risk factors. Endothelial function closely correlates with the number of circulating EPC providing new mechanistic insights and options for risk assessment in patients with coronary heart disease.

Key words

endothelial progenitor cells endothelial function atherosclerosis 

References

  1. 1.
    Asahara T, Murohara T, Sullivan A, Silver M, van der ZR, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967CrossRefPubMedGoogle Scholar
  2. 2.
    Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCAREAMI). Circulation 106:3009–3017CrossRefPubMedGoogle Scholar
  3. 3.
    Baumhäkel M, Werner N, Böhm M, Nickenig G (2006) Circulating endothelial progenitor cells correlate with erectile function in patients with coronary heart disease. Eur Heart J 27:2184–2188CrossRefPubMedGoogle Scholar
  4. 4.
    Fontaine V, Filipe C, Werner N, Gourdy P, Billon A, Garmy-Susini B, Brouchet L, Bayard F, Prats H, Doetschman T, Nickenig G, Arnal JF (2006) Essential role of bone marrow fibroblast growth factor- 2 in the effect of estradiol on reendothelialization and endothelial progenitor cell mobilization. Am J Pathol 169:1855–1862CrossRefPubMedGoogle Scholar
  5. 5.
    Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N (2006) CD34-CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res 98:e20–e25CrossRefPubMedGoogle Scholar
  6. 6.
    Heeschen C, Lehmann R, Honold J, Assmus B, Aicher A, Walter DH, Martin H, Zeiher AM, Dimmeler S (2004) Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 109:1615–1622CrossRefPubMedGoogle Scholar
  7. 7.
    Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T (2001) Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104:2673–2678CrossRefPubMedGoogle Scholar
  8. 8.
    Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348:593–600CrossRefPubMedGoogle Scholar
  9. 9.
    Landmesser U, Hornig B, Drexler H (2004) Endothelial function: a critical determinant in atherosclerosis? Circulation 109:II27–II33CrossRefPubMedGoogle Scholar
  10. 10.
    Laufs U, Werner N, Link A, Endres M, Wassmann S, Jurgens K, Miche E, Böhm M, Nickenig G (2004) Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation 109:220–226CrossRefPubMedGoogle Scholar
  11. 11.
    Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874CrossRefPubMedGoogle Scholar
  12. 12.
    Libby P, Sukhova G, Lee RT, Liao JK (1997) Molecular biology of atherosclerosis. Int J Cardiol 62(Suppl 2):S23–S29CrossRefPubMedGoogle Scholar
  13. 13.
    Lyngbaek S, Schneider M, Hansen JL, Sheikh SP (2007) Cardiac regeneration by resident stem and progenitor cells in the adult heart. Basic Res Cardiol 102:101–114CrossRefPubMedGoogle Scholar
  14. 14.
    Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA (2003) Aging, progenitor cell exhaustion, and atherosclerosis. Circulation 108:457–463CrossRefPubMedGoogle Scholar
  15. 15.
    Ross R (1999) Atherosclerosis — an inflammatory disease. N Engl J Med 340:115–126CrossRefPubMedGoogle Scholar
  16. 16.
    Rossig L, Dimmeler S, Zeiher AM (2001) Apoptosis in the vascular wall and atherosclerosis. Basic Res Cardiol 96:11–22CrossRefPubMedGoogle Scholar
  17. 17.
    Schachinger V, Britten MB, Zeiher AM (2000) Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 101:1899–1906PubMedGoogle Scholar
  18. 18.
    Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM (2006) Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210–1221CrossRefPubMedGoogle Scholar
  19. 19.
    Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, Kogler G, Wernet P (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918CrossRefPubMedGoogle Scholar
  20. 20.
    Strehlow K,Werner N, Berweiler J, Link A, Dirnagl U, Priller J, Laufs K,Ghaeni L, Milosevic M, Böhm M, Nickenig G (2003) Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation. Circulation 107:3059–3065CrossRefPubMedGoogle Scholar
  21. 21.
    Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR, Jr., Lerman A (2000) Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 101:948–954PubMedGoogle Scholar
  22. 22.
    Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353CrossRefPubMedGoogle Scholar
  23. 23.
    Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89:E1–E7CrossRefPubMedGoogle Scholar
  24. 24.
    Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, Nishimura H, Losordo DW, Asahara T, Isner JM (2002) Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 105:3017–3024CrossRefPubMedGoogle Scholar
  25. 25.
    Wassmann S, Nickenig G (2003) Inter-relationship of free oxygen radicals and endothelial dysfunction–modulation by statins. Endothelium 10:23–33CrossRefPubMedGoogle Scholar
  26. 26.
    Wassmann S, Werner N, Czech T, Nickenig G (2006) Improvement of endothelial function by systemic transfusion of vascular progenitor cells. Circ Res 99:e74–e83CrossRefPubMedGoogle Scholar
  27. 27.
    Werner N, Junk S, Laufs U, Link A, Walenta K, Böhm M, Nickenig G (2003) Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res 93:e17–e24CrossRefPubMedGoogle Scholar
  28. 28.
    Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353:999–1007CrossRefPubMedGoogle Scholar
  29. 29.
    Werner N, Nickenig G (2006) Clinical and therapeutical implications of EPC biology in atherosclerosis. J Cell Mol Med 10:318–332CrossRefPubMedGoogle Scholar
  30. 30.
    Werner N, Nickenig G (2006) Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy? Arterioscler Thromb Vasc Biol 26:257–266CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2007

Authors and Affiliations

  • Nikos Werner
    • 1
  • Sven Wassmann
    • 1
  • Patrick Ahlers
    • 1
  • Tobias Schiegl
    • 1
  • Sonja Kosiol
    • 1
  • Andreas Link
    • 2
  • Katrin Walenta
    • 2
  • Georg Nickenig
    • 1
  1. 1.Medizinische Klinik und Poliklinik IIUniversitätsklinikum BonnBonnGermany
  2. 2.Medizinische Klinik IIIUniversitätsklinikum Homburg SaarHomburg (Saar)Germany

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