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Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

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Abstract

Objectives

We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes.

Background

We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening.

Methods

Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 ± 1 years, n = 20) and older (61 ± 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR+/CD34+ and KDR+/CD133+) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival.

Results

We observed thicker IMT in older as compared to younger subjects (0.68 ± 0.03 mm Vs. 0.48 ± 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = −0.466 P < 0.05; r = −0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R = 0.58).

Conclusion

Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance.

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References

  1. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228

    PubMed  CAS  Google Scholar 

  2. Assmus B, Schaechinger V, Teupe C, Britten M, Lehmann R, Doebert N, Gruenwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM (2002) Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Intarction (TOPCARE-AMI). Circulation 106:3009–3017

    Article  PubMed  Google Scholar 

  3. Fadini GP, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A (2006) Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke 37:2277–2282

    Article  PubMed  CAS  Google Scholar 

  4. Grobbee DE, Bots ML (1994) Carotid artery intima-media thickness as an indicator of generalized atherosclerosis. J Intern Med 236:567–573

    Article  PubMed  CAS  Google Scholar 

  5. Heiss C, Amabile N, Lee AC, May Real W, Schick SF, Lao D, Wong ML, Jahn S, Angeli FS, Minasi P, Springer ML, Hammond SK, Glantz SA, Grossman W, Balmes JR, Yeghiazarians Y (2008) Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function. J Am Coll Cardiol 51:1760–1771

    Article  PubMed  CAS  Google Scholar 

  6. Heiss C, Keymel S, Niesler U, Ziemann J, Kelm M, Kalka C (2005) Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol 45:1441–1448

    Article  PubMed  CAS  Google Scholar 

  7. Hill JM, Zalos G, Halcox JPJ, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348:593–600

    Article  PubMed  Google Scholar 

  8. Lyngbaek S, Schneider M, Hansen JL, Sheikh SP (2007) Cardiac regeneration by resident stem and progenitor cells in the adult heart. Basic Res Cardiol 102:101–114

    Article  PubMed  Google Scholar 

  9. 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 108:457–463

    Article  PubMed  Google Scholar 

  10. Ross R (1986) The pathogenesis of atherosclerosis—an update. N Engl J Med 314:488–500

    PubMed  CAS  Google Scholar 

  11. Schuh A, Liehn E, Sasse A, Hristov M, Sobota R, Kelm M, Merx M, Weber C (2007) Transplantation of endothelial progenitor cells improves neovascularization and left ventricular function after myocardial infarction in a rat model. Basic Res Cardiol 103:69–77

    Article  PubMed  Google Scholar 

  12. Thum T, Hoeber S, Froese S, Klink I, Stichtenoth DO, Galuppo P, Jakob M, Tsikas D, Anker SD, Poole-Wilson PA, Borlak J, Ertl G, Bauersachs J (2007) Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulin-like growth-factor-1. Circ Res 100:434–443

    Article  PubMed  CAS  Google Scholar 

  13. 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–e7

    Article  PubMed  CAS  Google Scholar 

  14. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353:999–1007

    Article  PubMed  CAS  Google Scholar 

  15. Werner N, Wassmann S, Ahlers P, Schiegl T, Kosiol S, Link A, Walenta K, Nickenig G (2007) Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease. Basic Res Cardiol 102:565–571

    Article  PubMed  Google Scholar 

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Correspondence to Christian Heiss MD.

Additional information

Returned for 1. Revision: 13 December 2007 1. Revision received: 16 June 2008

Returned for 2. Revision: 20 June 2008 2. Revision received: 17 July 2008

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Keymel, S., Kalka, C., Rassaf, T. et al. Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening. Basic Res Cardiol 103, 582–586 (2008). https://doi.org/10.1007/s00395-008-0742-z

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  • DOI: https://doi.org/10.1007/s00395-008-0742-z

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