Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Prehypertension and endothelial progenitor cell function

Journal of Human Hypertension volume 25, pages 57–62 (2011)Cite this article

Subjects

Abstract

Prehypertension is associated with significant damage to the coronary vasculature and increased rates of adverse cardiovascular events. Circulating endothelial progenitor cells (EPCs) are critical to vascular repair and the formation of new blood vessels. We tested the hypothesis that prehypertension is associated with EPC dysfunction. Peripheral blood samples were collected from 83 middle-aged and older adults (51 male and 32 female): 40 normotensive subjects (age 53±2 years; BP 111/74±1/1 mm Hg) and 43 prehypertensive subjects (age 54±2 years; 128/77±1/1 mm Hg). EPCs were isolated from peripheral blood, and EPC colony-forming capacity (colony-forming unit (CFU) assay), migratory activity (Boyden chamber) and apoptotic susceptibility (active caspase-3 concentrations) were determined. There were no significant differences in the number of EPC CFUs (10±2 vs 9±1), EPC migration (1165±82 vs 1120±84 fluorescent units) or active intracellular caspase-3 concentrations (2.7±0.3 vs 2.3±0.2 ng ml−1) between the normotensive and prehypertensive groups. When groups were stratified into low prehypertension (n=27; systolic blood pressure: 120–129 mm Hg) and high prehypertension (n=16; 130–139 mm Hg), it was found that EPCs from the high prehypertensive group produced fewer (∼65%, P<0.05) CFUs compared with the low prehypertensive (4±1 vs 12±2) and normotensive adults. In conclusion, EPC colony-forming capacity is impaired only in prehypertensive adults with systolic BP greater than 130 mm Hg. Prehypertension is not associated with migratory dysfunction or enhanced apoptosis of EPCs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Wang Y, Wang QJ . The prevalence of prehypertension and hypertension among US adults according to the new joint national committee guidelines: new challenges of the old problem. Arch Intern Med 2004; 164 (19): 2126–2134.

    Article  Google Scholar 

  2. Qureshi AI, Suri MF, Kirmani JF, Divani AA, Mohammad Y . Is prehypertension a risk factor for cardiovascular diseases? Stroke 2005; 36 (9): 1859–1863.

    Article  Google Scholar 

  3. Erdogan D, Caliskan M, Yildirim I, Gullu H, Baycan S, Ciftci O et al. Effects of normal blood pressure, prehypertension and hypertension on left ventricular diastolic function and aortic elastic properties. Blood Press 2007; 16 (2): 114–121.

    Article  Google Scholar 

  4. Knight EL, Kramer HM, Curhan GC . High-normal blood pressure and microalbuminuria. Am J Kidney Dis 2003; 41 (3): 588–595.

    Article  Google Scholar 

  5. Dimmeler S, Zeiher AM . Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis? J Mol Med 2004; 82 (10): 671–677.

    Article  Google Scholar 

  6. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85 (3): 221–228.

    Article  CAS  Google Scholar 

  7. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002; 106 (24): 3009–3017.

    Article  Google Scholar 

  8. Kunz GA, Liang G, Cuculi F, Gregg D, Vata KC, Shaw LK et al. Circulating endothelial progenitor cells predict coronary artery disease severity. Am Heart J 2006; 152 (1): 190–195.

    Article  Google Scholar 

  9. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001; 89 (1): E1–E7.

    Article  CAS  Google Scholar 

  10. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353 (10): 999–1007.

    Article  CAS  Google Scholar 

  11. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289 (19): 2560–2572.

    Article  CAS  Google Scholar 

  12. Lohman T, Roche A, Mortorell R . Anthropometric Standardization Reference Manual. Human Kinetics: Champaign, IL, 1988.

    Google Scholar 

  13. DeSouza CA, Shapiro LF, Clevenger CM, Dinenno FA, Monahan KD, Tanaka H et al. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation 2000; 102: 1351–1357.

    Article  CAS  Google Scholar 

  14. MacEneaney OJ, Kushner EJ, Van Guilder GP, Greiner JJ, Stauffer BL, DeSouza CA . Endothelial progenitor cell number and colony-forming capacity in overweight and obese adults. Int J Obes (Lond) 2009; 33 (2): 219–225.

    Article  CAS  Google Scholar 

  15. Hoetzer GL, MacEneaney OJ, Irmiger HM, Keith R, Van Guilder GP, Stauffer BL et al. Gender differences in circulating endothelial progenitor cell colony-forming capacity and migratory activity in middle-aged adults. Am J Cardiol 2007; 99 (1): 46–48.

    Article  Google Scholar 

  16. Chobanian AV . Prehypertension revisited. Hypertension 2006; 48 (5): 812–814.

    Article  CAS  Google Scholar 

  17. Gu Q, Burt VL, Paulose-Ram R, Yoon S, Gillum RF . High blood pressure and cardiovascular disease mortality risk among U.S. adults: the third National Health and Nutrition Examination Survey mortality follow-up study. Ann Epidemiol 2008; 18 (4): 302–309.

    Article  Google Scholar 

  18. Vasan RS, Larson MG, Leip EP, Evans JC, O'Donnell CJ, Kannel WB et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001; 345 (18): 1291–1297.

    Article  CAS  Google Scholar 

  19. Imanishi T, Moriwaki C, Hano T, Nishio I . Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens 2005; 23 (10): 1831–1837.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  21. Delva P, Degan M, Vallerio P, Arosio E, Minuz P, Amen G et al. Endothelial progenitor cells in patients with essential hypertension. J Hypertens 2007; 25 (1): 127–132.

    Article  CAS  Google Scholar 

  22. Stamler J, Stamler R, Neaton JD . Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993; 153 (5): 598–615.

    Article  CAS  Google Scholar 

  23. He J, Whelton PK . Elevated systolic blood pressure and risk of cardiovascular and renal disease: overview of evidence from observational epidemiologic studies and randomized controlled trials. Am Heart J 1999; 138 (3 Part 2): 211–219.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, Schmitt J et al. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 2003; 108 (18): 2212–2218.

    Article  CAS  Google Scholar 

  26. Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5 (4): 434–438.

    Article  CAS  Google Scholar 

  27. Chrysohoou C, Panagiotakos DB, Pitsavos C, Skoumas J, Economou M, Papadimitriou L et al. The association between pre-hypertension status and oxidative stress markers related to atherosclerotic disease: the ATTICA study. Atherosclerosis 2007; 192 (1): 169–176.

    Article  CAS  Google Scholar 

  28. Julius S, Nesbitt S, Egan B, Kaciroti N, Schork MA, Grozinski M et al. Trial of preventing hypertension: design and 2–year progress report. Hypertension 2004; 44 (2): 146–151.

    Article  CAS  Google Scholar 

  29. Imanishi T, Hano T, Sawamura T, Nishio I . Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction. Clin Exp Pharmacol Physiol 2004; 31 (7): 407–413.

    Article  CAS  Google Scholar 

  30. Imanishi T, Hano T, Nishio I . Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress. J Hypertens 2005; 23 (1): 97–104.

    Article  CAS  Google Scholar 

  31. Yu Y, Fukuda N, Yao EH, Matsumoto T, Kobayashi N, Suzuki R et al. Effects of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension. Am J Hypertens 2008; 21 (1): 72–77.

    Article  CAS  Google Scholar 

  32. Ito H, Rovira II, Bloom ML, Takeda K, Ferrans VJ, Quyyumi AA et al. Endothelial progenitor cells as putative targets for angiostatin. Cancer Res 1999; 59 (23): 5875–5877.

    CAS  PubMed  Google Scholar 

  33. Hur J, Yang HM, Yoon CH, Lee CS, Park KW, Kim JH et al. Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies. Circulation 2007; 116 (15): 1671–1682.

    Article  Google Scholar 

  34. Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H et al. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 1999; 18 (14): 3964–3972.

    Article  CAS  Google Scholar 

  35. Chade AR, Zhu X, Lavi R, Krier JD, Pislaru S, Simari RD et al. Endothelial progenitor cells restore renal function in chronic experimental renovascular disease. Circulation 2009; 119 (4): 547–557.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank all the subjects who participated in the study, as well as Yoli Casas and Jeremy Stoner for their technical assistance. This study was supported by the National Institutes of Health Awards HL068030, DK062061, HL076434 and MO1 #RR00051.

Author information

Authors and Affiliations

  1. Department of Integrative Physiology, Integrative Vascular Biology Laboratory, University of Colorado, Boulder, CO, USA

    O J MacEneaney, C A DeSouza, B R Weil, E J Kushner, G P Van Guilder, M L Mestek, J J Greiner & B L Stauffer

  2. Department of Medicine, University of Colorado, Denver, Colorado, USA

    C A DeSouza & B L Stauffer

  3. Denver Health Medical Center, Denver, CO, USA

    B L Stauffer

Authors
  1. O J MacEneaney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C A DeSouza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B R Weil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E J Kushner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G P Van Guilder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M L Mestek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J J Greiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B L Stauffer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C A DeSouza.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

MacEneaney, O., DeSouza, C., Weil, B. et al. Prehypertension and endothelial progenitor cell function. J Hum Hypertens 25, 57–62 (2011). https://doi.org/10.1038/jhh.2010.31

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2010.31

Keywords

This article is cited by

Search

Advanced search

Quick links