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Vol. 33, No. 6, 2011
Issue release date: June 2011
Am J Nephrol 2011;33:550–557
(DOI:10.1159/000328632)

ARB Treatment Prevents the Decrease in Endothelial Progenitor Cells and the Loss of Renal Microvasculature in Remnant Kidney

Yu Y. · Wang Y. · Zhou L. · Zheng F.
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Abstract

Background: Endothelial progenitor cells (EPCs) are involved in endothelium turnover and play a role in renal capillary repair. Since angiotensin II has been shown to negatively affect EPCs and blockade of angiotensin II decreases the progression of renal diseases, we investigated the effects of losartan on EPCs and renal endothelial cells in remnant kidney. Methods: Sprague-Dawley rats were randomized to receive losartan (25 mg/kg/day) or solvent for 15 weeks after 5/6 nephrectomy. Peripheral blood CD34+ EPCs were counted and the number of CD31+ endothelial colonies was determined. Glomerular and tubulointerstitial capillary endothelial cells were assessed and vascular endothelial growth factor (VEGF) and thrombospondin (TSP-1) expression were determined. Results: EPCs and the number of endothelial colonies were significantly reduced in 5/6 nephrectomized rats, which was associated with a decrease in glomerular and tubulointerstitial endothelial cells, a decrease in VEGF and an increase in TSP-1 expression. Losartan treatment largely prevented changes in both EPCs and remnant kidney. Conclusion: The gradual loss of renal capillaries in remnant kidney was associated with decreased EPCs and endothelial colonies, hindering capillary endothelial repair in remnant kidney. Losartan treatment largely prevented the loss of EPCs and preserved renal endothelial cells, which may be part of the mechanism of how it contributes to renal protection.



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References

  1. Kang DH, Kanellis J, Hugo C, Truong L, Anderson S, Kerjaschki D, Schreiner GF, Johnson RJ: Role of the microvascular endothelium in progressive renal disease. J Am Soc Nephrol 2002;13:806–816.
  2. Molitoris BA, Sutton TA: Endothelial injury and dysfunction: role in the extension phase of acute renal failure. Kidney Int 2004;66:496–499.
  3. Ostendorf T, Kunter U, Eitner F, Loos A, Regele H, Kerjaschki D, Henninger DD, Janjic N, Floege J: VEGF(165) mediates glomerular endothelial repair. J Clin Invest 1999;104:913–923.
  4. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27–31.
  5. 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;275:964–967.
  6. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.
  7. 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;23:1831–1837.
  8. Tongesrs J, Losordo DW: Frontiers in nephrology: the evolving therapeutic applications of endothelial progenitor cells. J Am Soc Nephrol 2007;18:2843–2852.
  9. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T: Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003;348:593–600.
  10. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S: Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001;89:E1–E7.
  11. Deng A, Arndt MA, Satriano J, Singh P, Rieg T, Thomson S, Tang T, Blantz RC: Renal protection in chronic kidney disease: hypoxia-inducible factor activation vs. angiotensin II blockade. Am J Physiol Renal Physiol 2010;299:F1365–F1373.
  12. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851–860.
  13. Liang XB, Ma LJ, Naito T, Wang Y, Madaio M, Zent R, Pozzi A, Fogo AB: Angiotensin type 1 receptor blocker restores podocyte potential to promote glomerular endothelial cell growth. J Am Soc Nephrol 2006;17:1886–1895.
  14. Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, Nishimura H, Losordo DW, Asahara T, Isner JM: Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 2002;105:3017–3024.
  15. Pillebout E, Burtin M, Yuan HT, Briand P, Woolf AS, Friedlander G, Terzi F: Proliferation and remodeling of the peritubular microcirculation after nephron reduction. Am J Physiol 2001;159:547–560.
  16. Ulger H, Karabulut AK, Pratten MK: Labelling of rat endothelial cells with antibodies to vWF, RECA-1, PECAM-1, ICAM-1, OX-43 and ZO-1. Anat Histol Embryol 2002;31:31–35.
  17. Matsui K, Nagy-Bojarsky K, Laakkonen P, Krieger S, Mechtler K, Uchida S, Geleff S, Kang DH, Johnson RJ, Kerjaschki D: Lymphatic microvessels in the rat remnant kidney model of renal fibrosis: aminopeptidase p and podoplanin are discriminatory markers for endothelial cells of blood and lymphatic vessels. J Am Soc Nephrol 2003;14:1981–1989.
  18. Kang DH, Joly AH, Oh SW, Hugo C, Kerjaschki D, Gordon KL, Mazzali M, Jefferson JA, Hughes J, Madsen KM, Schreiner GF, Johnson RJ: Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. J Am Soc Nephrol 2001;12:1434–1447.
  19. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G: Circulating endothelial progenitors cells and cardiovascular outcomes. N Engl J Med 2005;353:999–1007.
  20. Rosenzweig A: Circulating endothelial progenitors cells as biomarkers. N Engl J Med 2005;353:1055–1057.
  21. Yu Y, Fukuda N, Yao EH, Matsumoto T, Kobayashi N, Suzuki R, Tahira Y, Ueno T, Matsumoto K: Effect of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension. Am J Hypertens 2008;21:72–77.
  22. Rafii S, Lyden D: Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 2003;9:702–712.
  23. Kelly DJ, Hepper C, Wu LL, Cox AJ, Gilbert RE: Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model. Nephrol Dial Transplant 2003;18:1286–1292.
  24. Spyridopoulos I, Brogi E, Kearney M, Sullivan AB, Cetrulo C, Isner JM, Losordo DW: Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: balance between growth and death signals. J Mol Cell Cardiol 1997;29:1321–1330.
  25. Masuda Y, Shimizu A, Mori T, Ishiwata T, Kitamura H, Ohashi R, Ishizaki M, Asano G, Sugisaki Y, Yamanaka N: Vascular endothelial growth factor enhances glomerular capillary capillary repair and accelerates resolution of experimentally induced glomerulonephritis. Am J Pathol 2001;159:599–608.
  26. Aicher A, Zeiher AM, Dimmeler S: Mobilizing endothelial progenitor cells. Hypertension 2005;45:321–325.
  27. Sun J, Hopkins BD, Tsujikawa K, Perruzzi C, Adini I, Swerlick R, Bornstein P, Lawler J, Benjamin LE: Thrombospondin-1 modulates VEGF-A-mediated Akt signaling and capillary survival in the developing retina. Am J Physiol Heart Circ Physiol 2009;296:H1344–H1351.
  28. Mirochnik Y, Kwiatek A, Volpert OV: Thrombospondin and apoptosis: molecular mechanisms and use for design of complementation treatments. Curr Drug Targets 2008;9:851–862.
  29. Hugo C, Shankland SJ, Pichler RH, Couser WG, Johnson RJ: Thrombospondin 1, a TGF-β activating protein, precedes and predicts the development of tubulointerstitial fibrosis in glomerular disease. Kidney Int 1998;53:302–311.


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