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Endothelial Dysfunction and Nitric Oxide: Albuminuria as a Central Marker

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Cardio-Nephrology

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Abstract

The endothelium is the largest organ in the body strategically located between the wall of blood vessels and the blood stream. The principal physiologic stimulus for endothelial nitric oxide (NO) synthesis is blood flow-induced shear stress, a process termed “flow-mediated vasodilatation”, which is a clinical assessment of endothelial well-being. Endothelial cell damage or injury is invariably associated with thrombosis, hypertension, and atherosclerosis. Albuminuria has been associated with cardiovascular disease that is synergistic with conventional risk factors in both nondiabetic and diabetic patients. The mechanism by which albuminuria is associated with cardiovascular disease is not well understood, however, the presence of albuminuria signals impaired endothelial function. In this chapter, the mechanisms of endothelial dysfunction, including the contributing role of albuminuria are discussed.

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References

  1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–6.

    Article  CAS  PubMed  Google Scholar 

  2. Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002;105:546–9.

    Article  CAS  PubMed  Google Scholar 

  3. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–7.

    Article  CAS  PubMed  Google Scholar 

  4. Schwartz SM, Gajdusek CM, Reidy MA, Selden SC 3rd, Haudenschild CC. Maintenance of integrity in aortic endothelium. Fed Proc. 1980;39:2618–25.

    CAS  PubMed  Google Scholar 

  5. Bombeli T, Mueller M, Haeberli A. Anticoagulant properties of the vascular endothelium. Thromb Haemost. 1997;77:408–23.

    CAS  PubMed  Google Scholar 

  6. Jarray R, Pavoni S, Borriello L, Allain B, Lopez N, Bianco S, Liu WQ, Biard D, Demange L, Hermine O, Garbay C, Raynaud F, Lepelletier Y. Disruption of phactr-1 pathway triggers pro-inflammatory and pro-atherogenic factors: new insights in atherosclerosis development. Biochimie. 2015;118:151–61.

    Article  CAS  PubMed  Google Scholar 

  7. Kerr H, Richards A. Complement-mediated injury and protection of endothelium: lessons from atypical haemolytic uraemic syndrome. Immunobiology. 2012;217:195–203.

    Article  CAS  PubMed  Google Scholar 

  8. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.

    Article  CAS  PubMed  Google Scholar 

  9. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046–51.

    Article  CAS  PubMed  Google Scholar 

  10. Zoccali C, Bode-Böger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, Cataliotti A, Bellanuova I, Fermo I, Frölich J, Böger R. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet. 2001;358:2113–7.

    Article  CAS  Google Scholar 

  11. Shantsila E, Blann AD, Lip GY. Circulating endothelial cells: from bench to clinical practice. J Thromb Haemost. 2008;6:865–8.

    Article  CAS  PubMed  Google Scholar 

  12. Takahashi T, Harris RC. Role of endothelial nitric oxide synthase in diabetic nephropathy: lessons from diabetic eNOS knockout mice. J Diabetes Res. 2014;2014:590541.

    Article  PubMed  PubMed Central  Google Scholar 

  13. KDIGO. Chapter 1: definition and classification of CKD. Kidney Int Suppl 2013;3:19. http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf. Accessed 29 Jan 2016.

  14. Glassock RJ. Debate: CON position. Should microalbuminuria ever be considered as a renal endpoint in any clinical trial? Am J Nephrol. 2010;31:462–5.

    Article  PubMed  Google Scholar 

  15. Comper WD, Hilliard LM, Nikolic-Paterson DJ, Russo LM. Disease-dependent mechanisms of albuminuria. Am J Physiol Renal Physiol. 2008;295:1589–600.

    Article  Google Scholar 

  16. Stehouwer CD, Henry RM, Dekker JM, Nijpels G, Heine RJ, Bouter LM. Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction—the Hoorn Study. Kidney Int. 2004;92(Suppl):S42–44.

    Article  Google Scholar 

  17. Stenvinkel P, Carrero JJ, Axelsson J, Lindholm B, Heimburger O, Massy Z. Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle? Clin J Am Soc Nephrol. 2008;3:505–21.

    Article  CAS  PubMed  Google Scholar 

  18. Mogensen CE, Vestbo E, Poulsen PL, Christiansen C, Damsgaard EM, Eiskjaer H, Frøland A, Hansen KW, Nielsen S, Pedersen MM. Microalbuminuria and potential confounders. A review and some observations on variability of urinary albumin excretion. Diabetes Care. 1995;18:572–81.

    Article  CAS  PubMed  Google Scholar 

  19. Tani Y, Nakayama M, Terawaki H, Iseki K, Watanabe T. Comparison of albuminuria test and urine test strip in Japanese hypertensive patients: AVA-E study. Clin Nephrol. 2015;84:270–3.

    Article  CAS  PubMed  Google Scholar 

  20. Witte EC, Lambers Heerspink HJ, de Zeeuw D, Bakker SJ, de Jong PE, Gansevoort R. First morning voids are more reliable than spot urine samples to assess microalbuminuria. J Am Soc Nephrol. 2009;20:436–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bartz SK, Caldas MC, Tomsa A, Krishnamurthy R, Bacha F. Urine albumin-to-creatinine ratio: a marker of early endothelial dysfunction in youth. J Clin Endocrinol Metab. 2015;100:3393–9.

    Article  CAS  PubMed  Google Scholar 

  22. Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, Gans RO, Janssen WM, Grobbee DE, de Jong PE, Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation. 2002;106:1777–82.

    Article  CAS  PubMed  Google Scholar 

  23. Roest M, Banga JD, Janssen WM, Grobbee DE, Sixma JJ, de Jong PE, de Zeeuw D, van Der Schouw YT. Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women. Circulation. 2001;103:3057–61.

    Article  CAS  PubMed  Google Scholar 

  24. Rabelink TJ, de Zeeuw D. The glycocalyx-linking albuminuria with renal and cardiovascular disease. Nat Rev Nephrol. 2015;11:667–76.

    Article  CAS  PubMed  Google Scholar 

  25. Fu J, Lee K, Chuang PY, Liu Z, He JC. Glomerular endothelial cell injury and cross talk in diabetic kidney disease. Am J Physiol Renal Physiol. 2015;308(4):F287–97.

    Article  CAS  PubMed  Google Scholar 

  26. Satchell S. The role of the glomerular endothelium in albumin handling. Nat Rev Nephrol. 2013;9:717–25.

    Article  CAS  PubMed  Google Scholar 

  27. Siddiqi FS, Advani A. Endothelial–podocyte crosstalk: the missing link between endothelial dysfunction and albuminuria in diabetes. Diabetes. 2013;62:3647–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Khaleghi M, Singletary LA, Kondragunta V, Bailey KR, Turner ST, Mosley TH Jr, Kullo IJ. Haemostatic markers are associated with measures of vascular disease in adults with hypertension. J Hum Hypertens. 2009;23:530–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Petrica L, Vlad A, Gluhovschi G, Gadalean F, Dumitrascu V, Vlad D, Popescu R, Velciov S, Gluhovschi C, Bob F, Ursoniu S, Petrica M, Jianu DC. Glycated peptides are associated with the variability of endothelial dysfunction in the cerebral vessels and the kidney in type 2 diabetes mellitus patients: a cross-sectional study. J Diabetes Compl. 2015;29:230–7.

    Article  Google Scholar 

  30. Park M, Vittinghoff E, Ganz P, Peralta CA, Whooley M, Shlipak MG. Role of soluble endothelial cell-selective adhesion molecule biomarker in albuminuria and kidney function changes in patients with coronary artery disease: the Heart and Soul Study. Arterioscler Thromb Vasc Biol. 2014;34:231–6.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Second Department of Nephrology, Medical University, Sklodowskiej-Curie 24a, 15-276, Białystok, Poland

    Jolanta Malyszko

  2. Department of Invasive Cardiology, Medical University, Sklodowskiej-Curie 24a, 15-276, Białystok, Poland

    Hanna Bachorzewska-Gajewska

  3. First Department of Nephrology, Medical University, Zurawia 14, 15-276, Białystok, Poland

    Jacek Malyszko

Authors
  1. Jolanta Malyszko
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  2. Hanna Bachorzewska-Gajewska
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  3. Jacek Malyszko
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Correspondence to Jolanta Malyszko .

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, Einstein Medical Center, Sidney Kimmel College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Janani Rangaswami

  2. Department of Medicine, Section of Nephrology, University of Illinois at Chicago, Chicago, Illinois, USA

    Edgar V. Lerma

  3. Department of Nephrology Dialysis and Transplantation, International Renal Research Institute, San Bortolo Hospital, Vicenza, Italy

    Claudio Ronco

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Malyszko, J., Bachorzewska-Gajewska, H., Malyszko, J. (2017). Endothelial Dysfunction and Nitric Oxide: Albuminuria as a Central Marker. In: Rangaswami, J., Lerma, E., Ronco, C. (eds) Cardio-Nephrology. Springer, Cham. https://doi.org/10.1007/978-3-319-56042-7_1

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  • DOI: https://doi.org/10.1007/978-3-319-56042-7_1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56040-3

  • Online ISBN: 978-3-319-56042-7

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