Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia

Circulation Research
Norifumi UraoHiroaki Matsubara

Abstract

We investigated whether the mobilization of endothelial progenitor cells (EPCs) by exogenous erythropoietin (Epo) promotes the repair of injured endothelium. Recombinant human Epo was injected (1000 IU/kg for the initial 3 days) after wire injury of the femoral artery of mice. Neointimal formation was inhibited by Epo to 48% of the control (P<0.05) in an NO-dependent manner. Epo induced a 1.4-fold increase in reendothelialized area of day 14 denuded vessels, 55% of which was derived from bone marrow (BM) cells. Epo increased the circulating Sca-1(+)/Flk-1(+) EPCs (2.0-fold, P<0.05) with endothelial properties NO dependently. BM replacement by GFP- or beta-galactosidase-overexpressing cells showed that Epo stimulated both differentiation of BM-derived EPCs and proliferation of resident ECs. BM-derived ECs increased 2.2- to 2.7-fold (P<0.05) in the Epo-induced neoendothelium, where the expression of Epo receptor was upregulated. Epo induced Akt/eNOS phosphorylation and NO synthesis on EPCs and exerted an antiapoptotic action on wire-injured arteries. In conclusion, Epo treatment inhibits the neointimal hyperplasia after arterial injury in an NO-dependent manner by acting on the injured vessels and mobilizing EPCs to the neo-endot...Continue Reading

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References

Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A AnagnostouM Steiner
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·A AnagnostouC T Noguchi
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·B P ZambrowiczP Soriano
May 5, 1997·FEBS Letters·M OkabeY Nishimune
Feb 13, 1999·Kidney International·R G CarliniE Bellorin-Font
Oct 4, 2003·Blood·Ferdinand H BahlmannDanilo Fliser
Nov 1, 2005·Journal of the American College of Cardiology·Jonathan M HillRichard O Cannon

❮ Previous
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Citations

Feb 25, 2011·Basic Research in Cardiology·Ruifeng TengConstance Tom Noguchi
Jul 17, 2008·Cardiovascular Drugs and Therapy·Natalia Landázuri, W Robert Taylor
Mar 14, 2008·Journal of Thrombosis and Thrombolysis·Francesca MarzoFelicita Andreotti
May 26, 2011·Current Diabetes Reports·Lynn C ShawMaria B Grant
Dec 2, 2008·Expert Reviews in Molecular Medicine·Constance Tom NoguchiYi Jia
Jun 15, 2011·Chemical Reviews·Achala de MelAlexander M Seifalian
Mar 21, 2008·Journal of Neurotrauma·Nadeem I ShafiRobert M Bryan
Jan 12, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Andrzej SurdackiJacek S Dubiel
Oct 9, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Daphna LaifenfeldMichael P Lawton
May 7, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yi JiaConstance Tom Noguchi
Sep 8, 2010·Clinical and Experimental Pharmacology & Physiology·Hiroe TobaTetsuo Nakata
Jul 2, 2010·Diabetes, Obesity & Metabolism·G P Fadini, A Avogaro
Jun 21, 2011·Seminars in Dialysis·Noémie Jourde-ChichePhilippe Brunet
May 9, 2012·Anatomy Research International·Mawadda AlnaeeliConstance Tom Noguchi
Aug 13, 2009·Developmental Neuroscience·Fernando F GonzalezDonna M Ferriero
Mar 17, 2007·Circulation Research·Paolo Madeddu, Costanza Emanueli
Jan 26, 2008·The Journal of Clinical Investigation·Maria B GrantAlexander V Ljubimov
Sep 29, 2012·Critical Care : the Official Journal of the Critical Care Forum·Oscar McCookPeter Radermacher
Sep 14, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Norimasa TaniguchiHiroaki Matsubara
Oct 22, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Yoshihiko Saito
Nov 1, 2011·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Mariusz KowalczykJacek Rysz
Jul 23, 2013·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Piotr BartnickiJacek Rysz
Aug 27, 2009·Biologics : Targets & Therapy·Ana VillegasSantiago Redondo
Apr 21, 2009·Haematologica·Silvia Heringer-WaltherThomas Walther
Jun 21, 2008·International Journal of Biological Sciences·Nikolaos PaschosAlexandros E Beris
Nov 21, 2012·Regenerative Medicine·Robert C RennertGeoffrey C Gurtner
Feb 27, 2013·Heart Views : the Official Journal of the Gulf Heart Association·Sazzli KasimEugene McFadden
Feb 13, 2014·Microvascular Research·Bojana B Beleslin CokicConstance Tom Noguchi
May 30, 2013·Blood Cells, Molecules & Diseases·D BarthelmesW Y Shen
Jul 24, 2015·Hepatology International·Chandan Kumar KedarisettyShiv Kumar Sarin
Apr 8, 2014·Stem Cells and Development·Na ZhangJian-An Wang
Dec 10, 2014·Journal of Cardiovascular Pharmacology·Livius V dʼUscioZvonimir S Katusic
Dec 3, 2013·Canadian Journal of Physiology and Pharmacology·Simon ChiangAdria Giacca
Nov 5, 2011·Heart Failure Reviews·Lindsey Tilling, Brian Clapp

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