Zeitschrift für Gerontologie und Geriatrie

, Volume 46, Issue 7, pp 635–638 | Cite as

Redox balance in the aged endothelium

  • P. Czypiorski
  • L.L. Rabanter
  • J. Altschmied
  • J. Haendeler
Beiträge zum Themenschwerpunkt


The endothelium is located in a strategic anatomical position within the blood vessel wall and thus constitutes a barrier between the blood and all tissues. The integrity of the endothelial cells, which line the entire circulatory system like wallpaper, is essential to prevent the onset of cardiovascular disorders. Aging is one of the major risk factors for the development of heart and vascular diseases. However, over the past years it has become clear that the functional capacity of endothelial cells declines with age and that physiological aging occurs independently of pathological changes. One important mechanism contributing to the onset of the aging process is the disturbance of the cellular redox homeostasis. Two key molecules involved in maintaining the delicate balance between oxidative and antioxidative systems are NADPH oxidase 4, an enzyme whose sole function is to produce reactive oxygen species and the oxidoreductase thioredoxin-1, which reduces oxidized proteins. Therefore, this review will focus on the role of these two proteins in cardiovascular aging.


Aging Endothelial cells NADPH oxidase 4 Oxidative stress Thioredoxin-1 

Redoxgleichgewicht im gealterten Endothel


Das Endothel befindet sich in einer strategischen anatomischen Position in der Blutgefäßwand und stellt somit die Barriere zwischen dem Blut und allen Geweben dar. Die Integrität der Endothelzellen, die das gesamte Kreislaufsystem wie eine Tapete auskleiden, ist essenziell für die Verhinderung kardiovaskulärer Erkrankungen. Alterung ist einer der Hauptrisikofaktoren für die Entwicklung von Herz- und Gefäßerkrankungen. Allerdings hat sich über die letzten Jahre gezeigt, dass die Funktionen von Endothelzellen mit zunehmendem Alter abnehmen und dass es – unabhängig von pathologischen Veränderungen – einen physiologischen Alterungsprozess gibt. Einer der wesentlichen Mechanismen, die zum Beginn des Alterungsprozesses beitragen, ist die Veränderung der zellulären Redoxhomöostase. Zwei Schlüsselmoleküle in der delikaten Balance zwischen oxidativen und antioxidativen Systemen sind die NADPH-Oxidase 4, ein Enzym, dessen einzige Funktion die Produktion reaktiver Sauerstoffspezies ist, und die Oxidoreduktase Thioredoxin-1, die oxidierte Proteine reduziert. Daher konzentriert sich dieser Übersichtsbeitrag auf die Rolle dieser beiden Proteine in der kardiovaskulären Alterung.


Alterung Endothelzellen NADPH-Oxidase 4 Oxidativer Stress Thioredoxin-1 


  1. 1.
    Altschmied J, Haendeler J (2009) Thioredoxin-1 and endothelial cell aging: role in cardiovascular diseases. Antioxid Redox Signal 11:1733–1740PubMedCrossRefGoogle Scholar
  2. 2.
    Babior BM, Kipnes RS, Curnutte JT (1973) Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 52:741–744PubMedCrossRefGoogle Scholar
  3. 3.
    Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313PubMedCrossRefGoogle Scholar
  4. 4.
    Fierro-Gonzalez JC, Gonzalez-Barrios M, Miranda-Vizuete A et al (2011) The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans. Biochem Biophys Res Commun 406:478–482PubMedCrossRefGoogle Scholar
  5. 5.
    Forstermann U, Munzel T (2006) Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 113:1708–1714PubMedCrossRefGoogle Scholar
  6. 6.
    Griendling KK, Minieri CA, Ollerenshaw JD et al (1994) Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74:1141–1148PubMedCrossRefGoogle Scholar
  7. 7.
    Haendeler J (2006) Nitric oxide and endothelial cell aging. Eur J Clin Pharmacol 62(Suppl 13):137–140CrossRefGoogle Scholar
  8. 8.
    Haendeler J, Eckers A, Lukosz M et al (2012) Endothelial NADPH oxidase 2—when does it matter in atherosclerosis? Cardiovasc Res 94:1–2PubMedCrossRefGoogle Scholar
  9. 9.
    Haendeler J, Hoffmann J, Diehl JF et al (2004) Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells. Circ Res 94:768–775PubMedCrossRefGoogle Scholar
  10. 10.
    Haendeler J, Popp R, Goy C et al (2005) Cathepsin D and H2O2 stimulate degradation of thioredoxin-1: implication for endothelial cell apoptosis. J Biol Chem 280:42945–42951PubMedCrossRefGoogle Scholar
  11. 11.
    Hoffmann J, Haendeler J, Aicher A et al (2001) Aging enhances the sensitivity of endothelial cells toward apoptotic stimuli: important role of nitric oxide. Circ Res 89:709–715PubMedCrossRefGoogle Scholar
  12. 12.
    Holmgren A (2000) Antioxidant function of thioredoxin and glutaredoxin systems. Antioxid Redox Signal 2:811–820PubMedCrossRefGoogle Scholar
  13. 13.
    Krause KH (2007) Aging: a revisited theory based on free radicals generated by NOX family NADPH oxidases. Exp Gerontol 42:256–262PubMedCrossRefGoogle Scholar
  14. 14.
    Lakatta EG (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part III: cellular and molecular clues to heart and arterial aging. Circulation 107:490–497PubMedCrossRefGoogle Scholar
  15. 15.
    Lauer T, Heiss C, Balzer J et al (2008) Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise. Basic Res Cardiol 103:291–297PubMedCrossRefGoogle Scholar
  16. 16.
    Lener B, Koziel R, Pircher H et al (2009) The NADPH oxidase Nox4 restricts the replicative lifespan of human endothelial cells. Biochem J 423:363–374PubMedCrossRefGoogle Scholar
  17. 17.
    Matsui M, Oshima M, Oshima H et al (1996) Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene. Dev Biol 178:179–185PubMedCrossRefGoogle Scholar
  18. 18.
    North BJ, Sinclair DA (2012) The intersection between aging and cardiovascular disease. Circ Res 110:1097–1108PubMedCrossRefGoogle Scholar
  19. 19.
    Powis G, Kirkpatrick DL (2007) Thioredoxin signaling as a target for cancer therapy. Curr Opin Pharmacol 7:392–397PubMedCrossRefGoogle Scholar
  20. 20.
    Strait JB, Lakatta EG (2012) Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 8:143–164PubMedCrossRefGoogle Scholar
  21. 21.
    Toda N (2012) Age-related changes in endothelial function and blood flow regulation. Pharmacol Ther 133:159–176PubMedCrossRefGoogle Scholar
  22. 22.
    Torgovnick A, Schiavi A, Maglioni S et al (2013) Healthy aging: what can we learn from C. elegans? Z Gerontol Geriatr 7 (this issue)Google Scholar
  23. 23.
    Watanabe R, Nakamura H, Masutani H et al (2010) Anti-oxidative, anti-cancer and anti-inflammatory actions by thioredoxin 1 and thioredoxin-binding protein-2. Pharmacol Ther 127:261–270PubMedCrossRefGoogle Scholar
  24. 24.
    Werner C, Hanhoun M, Widmann T et al (2008) Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. J Am Coll Cardiol 52:470–482PubMedCrossRefGoogle Scholar
  25. 25.
    Zschauer TC, Matsushima S, Altschmied J et al (2013) Interacting with thioredoxin-1-disease or no disease? Antioxid Redox Signal 18:1053–1062PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • P. Czypiorski
    • 2
  • L.L. Rabanter
    • 2
  • J. Altschmied
    • 2
  • J. Haendeler
    • 1
    • 2
  1. 1.Central Institute of Clinical Chemistry and Laboratory MedicineUniversity of DuesseldorfDuesseldorfGermany
  2. 2.Molecular Aging ResearchIUF-Leibniz Research Institute for Environmental MedicineDuesseldorfGermany

Personalised recommendations