Skip to main content
NCBI home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;10(2):318–332. doi: 10.1111/j.1582-4934.2006.tb00402.x

Clinical and therapeutical implications of EPC biology in atherosclerosis

N Werner 1,*, G Nickenig 1
PMCID: PMC3933124  PMID: 16796802

Abstract

Bone marrow-derived circulating endothelial progenitor cells have been succesfully used to enhance angiogenesis after tissue ischemia. The role of endothelial progenitor cells in endothelial cell homeostasis and their putative role in atherogenesis have been recently investigated. Cardiovascular risk factors negatively influence endothelial progenitor cell number and function while vasculoprotection e.g. by statins, estrogens and physical activity may be partly mediated by progenitor cells. Endogenous mobilization or injection of ex-vivo generated endothelial progenitor cells is associated with an enhanced reendothelialization, an improvement of endothelial function and reduced athersclerotic burden. In contrast, endothelial progenitor cells may promote plaque angiogenesis in animal models and may negatively influence plaque development and stability. However, in humans with coronary atherosclerotic disease, endothelial progenitor cells are a novel risk prdictor for cardiovascular mortality and morbidity. In this review we focus on the role of circulating endothelial progenitor cells in endothelial cell repair mechanisms at the vascular wall and their potentially protective and therapeutic role in atherosclerotic disease.

Keywords: endothelium, endothelial progenitor cells, atheroslerosis

References

  • 1.Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001;104:2673–8. doi: 10.1161/hc4601.099485. [DOI] [PubMed] [Google Scholar]
  • 2.Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000;101:1899–906. doi: 10.1161/01.cir.101.16.1899. [DOI] [PubMed] [Google Scholar]
  • 3.Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR, Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101:948–54. doi: 10.1161/01.cir.101.9.948. [DOI] [PubMed] [Google Scholar]
  • 4.Asahara T, Murohara T, Sullivan A, Silver M, van Der ZR, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7. doi: 10.1126/science.275.5302.964. [DOI] [PubMed] [Google Scholar]
  • 5.Roberts N, Jahangiri M, Xu Q. Progenitor cells in vascular disease. J Cell Mol Med. 2005;9:583–91. doi: 10.1111/j.1582-4934.2005.tb00490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Rumpold H, Wolf D, Koeck R, Gunsilius E. Endothelial progenitor cells: a source for therapeutic vasculogenesis. J Cell Mol Med. 2004;8:509–18. doi: 10.1111/j.1582-4934.2004.tb00475.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.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;85:221–8. doi: 10.1161/01.res.85.3.221. [DOI] [PubMed] [Google Scholar]
  • 8.Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res. 2004;95:343–53. doi: 10.1161/01.RES.0000137877.89448.78. [DOI] [PubMed] [Google Scholar]
  • 9.Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res. 2001;88:167–74. doi: 10.1161/01.res.88.2.167. [DOI] [PubMed] [Google Scholar]
  • 10.Handgretinger R, Gordon PR, Leimig T, Chen X, Buhring HJ, Niethammer D, Kuci S. Biology and plasticity of CD133+ hematopoietic stem cells. Ann N Y Acad Sci. 2003;996:141–51. doi: 10.1111/j.1749-6632.2003.tb03242.x. [DOI] [PubMed] [Google Scholar]
  • 11.Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med. 2003;9:702–12. doi: 10.1038/nm0603-702. [DOI] [PubMed] [Google Scholar]
  • 12.Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N. CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res. 2006;98:e20–5. doi: 10.1161/01.RES.0000205765.28940.93. [DOI] [PubMed] [Google Scholar]
  • 13.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:E1–7. doi: 10.1161/hh1301.093953. [DOI] [PubMed] [Google Scholar]
  • 14.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. doi: 10.1056/NEJMoa022287. [DOI] [PubMed] [Google Scholar]
  • 15.Imanishi T, Hano T, Nishio I. Angiotensin II potentiates vascular endothelial grwoth factor-induced proliferation and network formation of endothelial progenitor cells. Hypertens Res. 2004;27:101–8. doi: 10.1291/hypres.27.101. [DOI] [PubMed] [Google Scholar]
  • 16.Min TQ, Zhu CJ, Xiang WX, Hui ZJ, Peng SY. Improvement in endothelial progenitor cells from peripheral blood by ramipril therapy in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2004;18:203–9. doi: 10.1023/B:CARD.0000033641.33503.bd. [DOI] [PubMed] [Google Scholar]
  • 17.Loomans CJ, De Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, De Boer HC, Verhaar MC, Braam B, Rabelink TJ, Van Zonneveld AJ. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53:195–9. doi: 10.2337/diabetes.53.1.195. [DOI] [PubMed] [Google Scholar]
  • 18.Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002;106:2781–6. doi: 10.1161/01.cir.0000039526.42991.93. [DOI] [PubMed] [Google Scholar]
  • 19.Krankel N, Adams V, Linke A, Gielen S, Erbs S, Lenk K, Schuler G, Hambrecht R. Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arterioscler Thromb Vasc Biol. 2005;25:698–703. doi: 10.1161/01.ATV.0000156401.04325.8f. [DOI] [PubMed] [Google Scholar]
  • 20.Tamarat R, Silvestre JS, Ricousse-Roussanne S, Barateau V, Lecomte-Raclet L, Clergue M, Duriez M, Tobelem G, Levy BI. Impairment in ischemia-induced neovascularization in diabetes: bone marrow mononuclear cell dysfunction and therapeutic potential of placenta growth factor treatment. Am J Pathol. 2004;164:457–66. doi: 10.1016/S0002-9440(10)63136-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Wang CH, Ciliberti N, Li SH, Szmitko PE, Weisel RD, Fedak PW, AI Omran M, Cherng WJ, Li RK, Stanford WL, Verma S. Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy. Circulation. 2004;109:1392–400. doi: 10.1161/01.CIR.0000123231.49594.21. [DOI] [PubMed] [Google Scholar]
  • 22.Bahlamann FH, De Groot K, Mueller O, Hertel B, Haller H, Fliser D. Stimulation of endothelial progenitor cells: a new putative therapeutic effect of angiotensin II receptor antagonists. Hypertension. 2005;45:526–9. doi: 10.1161/01.HYP.0000159191.98140.89. [DOI] [PubMed] [Google Scholar]
  • 23.Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH, Zhu JH. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond) 2004;107:273–80. doi: 10.1042/CS20030389. [DOI] [PubMed] [Google Scholar]
  • 24.Wang X, Chen J, Tao Q, Zhu J, Shang Y. Effects of ox-LDL on number and activity of circulating endothelial progenitor cells. Drug Chem Toxicol. 2004;27:243–55. doi: 10.1081/dct-120037505. [DOI] [PubMed] [Google Scholar]
  • 25.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;31:407–413. doi: 10.1111/j.1440-1681.2004.04022.x. [DOI] [PubMed] [Google Scholar]
  • 26.Imanishi T, Hano T, Matsuo Y, Nishio I. Oxidized lowdensity lipoprotein inhibits vascular endothelial growth factor-induced endothelial progenitor cell differentiation. Clin Exp Pharmacol Physiol. 2003;30:665–70. doi: 10.1046/j.1440-1681.2003.03894.x. [DOI] [PubMed] [Google Scholar]
  • 27.Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM. HMG-CoA reductase inhibitors (statins) increse endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001;108:391–7. doi: 10.1172/JCI13152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, Iino S, Inden Y, Murohara T. Smoking cessation rapidly increase circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol. 2004;24:1442–7. doi: 10.1161/01.ATV.0000135655.52088.c5. [DOI] [PubMed] [Google Scholar]
  • 29.Wang X, Zhu J, Chen J, Shang Y. Effects of nicotine on the number and activity of circulating endothelial progenitor cells. J Clin Pharmacol. 2004;44:881–9. doi: 10.1177/0091270004267593. [DOI] [PubMed] [Google Scholar]
  • 30.Chen JZ, Zhu JH, Wang XX, Zhu JH, Xie XD, Sun J, Shang YP, Guo XG, Dai HM, Hu SJ. Effects of homocysteine on number and activity of endothelial progenitor cells from peripheral blood. J Mol Cell Cardiol. 2004;36:233–9. doi: 10.1016/j.yjmcc.2003.10.005. [DOI] [PubMed] [Google Scholar]
  • 31.Suh W, Kim KL, Choi JH, Lee YS, Lee JY, Kim JM, Jang HS, Shin IS, Lee JS, Byun J, Jeon ES, Kim DK. C-reactive protein impairs angiogenic functions and decreases the secretion of arteriogenic chemo-cytokines in human endothelial progenitor cells. Biochem Biophys Res Commun. 2004;321:65–71. doi: 10.1016/j.bbrc.2004.06.107. [DOI] [PubMed] [Google Scholar]
  • 32.Verma S, Kuliszewski MA, Li SH, Szmitko PE, Zucco L, Wang CH, Badiwala MV, Mickle DA, Weisel RD, Fedak PW, Stewart DJ, Kutryk MJ. C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation. 2004;109:2058–67. doi: 10.1161/01.CIR.0000127577.63323.24. [DOI] [PubMed] [Google Scholar]
  • 33.Laufs U, Wassmann S, Czech T, Munzel T, Eisenhauer M, Bohm M, Nickening G. Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis. Arterioscler Thromb Vasc Biol. 2005;25:809–14. doi: 10.1161/01.ATV.0000158311.24443.af. [DOI] [PubMed] [Google Scholar]
  • 34.Lauf U, Werner N, Link A, Endres M, Wassmann S, Jurgens K, Miche E, Bohm M, Nickenig G. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation. 2004;109:220–6. doi: 10.1161/01.CIR.0000109141.48980.37. [DOI] [PubMed] [Google Scholar]
  • 35.Sandri M, Adams V, Gielen S, Linke A, Lenk K, Krankel N, Lenz D, Erbs S, Scheinert D, Mohr FW, Schuler G, Hambrecht R. Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies. Circulation. 2005;111:3391–9. doi: 10.1161/CIRCULATIONAHA.104.527135. [DOI] [PubMed] [Google Scholar]
  • 36.Laufs U, Urhausen A, Werner N, Scharhag J, Heitz A, Kissner G, Bohm M, Kindermann W, Nickenig G. Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects. Eur J Cardiovasc Prev Rehabil. 2005;12:407–14. doi: 10.1097/01.hjr.0000174823.87269.2e. [DOI] [PubMed] [Google Scholar]
  • 37.Strehlow K, Werner N, Berweiler J, Link A, Dirnagl U, Priller J, Laufs K, Ghaeni L, Milosevic M, Bohm M, Nickenig G. Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation. Circulation. 2003;107:3059–65. doi: 10.1161/01.CIR.0000077911.81151.30. [DOI] [PubMed] [Google Scholar]
  • 38.Kong D, Melo LG, Gnecchi M, Zhang L, Mostoslavsky G, Liew CC, Pratt RE, Dzau VJ. Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injurd arteries. Circulation. 2004;110:2039–46. doi: 10.1161/01.CIR.0000143161.01901.BD. [DOI] [PubMed] [Google Scholar]
  • 39.Werner N, Priller J, Laufs U, Endres M, Bohm M, Dirnagl U, Nickenig G. Bone marrow-derived progenitor cells modulate vascular reendothelaization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler Tromb Vasc Biol. 2002;22:1567–72. doi: 10.1161/01.atv.0000036417.43987.d8. [DOI] [PubMed] [Google Scholar]
  • 40.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;105:3017–24. doi: 10.1161/01.cir.0000018166.84319.55. [DOI] [PubMed] [Google Scholar]
  • 41.George J, Herz I, Goldstein E, Abashidze S, Deutch V, Finkelstein A, Michowitz Y, Miller H, Keren G. Number and adhesive properties of circulating endothelial progenitor cells in patients with in-stent restenosis. Arterioscler Tromb Vasc Biol. 2003;23:e57–60. doi: 10.1161/01.ATV.0000107029.65274.db. [DOI] [PubMed] [Google Scholar]
  • 42.Aoki J, Serruys PW, van Beusekom H, Ong AT, McFadden EP, Sianos G, van der Giessen WJ, Regar E, de Feyter PJ, Davis HR, Rowland S, Kutryk MJ. Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. J Am Coll Cardiol. 2005;45:1574–9. doi: 10.1016/j.jacc.2005.01.048. [DOI] [PubMed] [Google Scholar]
  • 43.Shirota T, Yasui H, Matsuda T. Intralumenal tissue-engineered therapeutic stent using endothelial progenitor cell-inoculated hybrid tissue and in vitro performance. Tissue Eng. 2003;9:473–85. doi: 10.1089/107632703322066651. [DOI] [PubMed] [Google Scholar]
  • 44.Shirota T, Yasui H, Shimokawa H, Matsuda T. Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in vitro endothelialization on hybrid vascular tissue. Biomaterials. 2003;24:2295–302. doi: 10.1016/s0142-9612(03)00042-5. [DOI] [PubMed] [Google Scholar]
  • 45.Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–74. doi: 10.1038/nature01323. [DOI] [PubMed] [Google Scholar]
  • 46.Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation. 2003;108:457–63. doi: 10.1161/01.CIR.0000082924.75945.48. [DOI] [PubMed] [Google Scholar]
  • 47.Karra R, Vemullapalli S, Dong C, Herderick EE, Song X, Slosek K, Nevins JR, West M, Goldschmidt-Clermont PJ, Seo D. Molecular evidence for arterial repair in atherosclerosis. Proc Natl Acad Sci USA. 2005;102:16789–94. doi: 10.1073/pnas.0507718102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Op D, Musters M, Verrips T, Post JA, Braam B, van Riel N. Mathematical modeling of vascular endothelial layer maintenance: the role of endothelial cell division, progenitor cell homing, and telomere shortening. Am J Physiol Heart Circ Physiol. 2004;287:H2651–8. doi: 10.1152/ajpheart.00332.2004. [DOI] [PubMed] [Google Scholar]
  • 49.Stoll BR, Migliorini C, Kadambi A, Munn LL, Jain RK. 2003. A mathematical model of the contribution of endothelial progenitor cells to angiogenesis in tumors: implications for anti-angiogenic therapy Blood. [DOI] [PubMed]
  • 50.Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999–1007. doi: 10.1056/NEJMoa043814. [DOI] [PubMed] [Google Scholar]
  • 51.Moulton KS, Vakili K, Zurakowski D, Soliman M, Butterfield C, Sylvin E, Lo KM, Gillies S, Javaherian K, Folkman J. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci USA. 2003;100:4736–41. doi: 10.1073/pnas.0730843100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, Badimon JJ, O'Connor WN. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation. 2004;110:2032–8. doi: 10.1161/01.CIR.0000143233.87854.23. [DOI] [PubMed] [Google Scholar]
  • 53.Hu Y, Davison F, Zhang Z, Xu Q. Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells. Circulation. 2003;108:3122–7. doi: 10.1161/01.CIR.0000105722.96112.67. [DOI] [PubMed] [Google Scholar]
  • 54.Okazaki T, Ebihara S, Asada M, Kanda A, Sasaki H, Yamaya M. Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+ cells in cancer animal models. Int Immunol. 2006;18:1–9. doi: 10.1093/intimm/dxh334. [DOI] [PubMed] [Google Scholar]
  • 55.Zhang H, Vakil V, Braunstein M, Smith EL, Maroney J, Chen L, Dai K, Berenson JR, Hussain MM, Klueppelberg U, Norin AJ, Akman HO, Ozcelik T, Batuman OA. Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood. 2005;105:3286–94. doi: 10.1182/blood-2004-06-2101. [DOI] [PubMed] [Google Scholar]
  • 56.Hilbe W, Dirnhofer S, Oberwasserlechner F, Schmid T, Gunsilius E, Hilbe G, Woll E, Kahler CM. CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer. J Clin Pathol. 2004;57:965–9. doi: 10.1136/jcp.2004.016444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Ribatti D. The involvement of endothelial progenitor cells in tumor angiogenesis. J Cell Mol Med. 2004;8:294–300. doi: 10.1111/j.1582-4934.2004.tb00319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Lee IG, Chae SL, Kim JC. 2005. Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy Eye.
  • 59.Moldovan NI. Angiogenesis, l'enfant terrible of vascular biology is coming of age. J Cell Mol Med. 2005;9:775–6. doi: 10.1111/j.1582-4934.2005.tb00378.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Horstman LL, Jy W, Jimenez JJ, Ahn YS. Endothelial microparticles as markers of endothelial dysfunction. Front Biosci. 2004;9:1118–35. doi: 10.2741/1270. [DOI] [PubMed] [Google Scholar]
  • 61.Jimenez JJ, Jy W, Mauro LM, Soderland C, Horstman LL, Ahn YS. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res. 2003;109:175–80. doi: 10.1016/s0049-3848(03)00064-1. [DOI] [PubMed] [Google Scholar]
  • 62.Bernal-Mizrachi L, Jy W, Jimenez JJ, Pastor J, Mauro LM, Horstman LL, de Marchena E, Ahn YS. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. Am Heart J. 2003;145:962–70. doi: 10.1016/S0002-8703(03)00103-0. [DOI] [PubMed] [Google Scholar]
  • 63.Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM, Tedgui A. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation. 2000;101:841–3. doi: 10.1161/01.cir.101.8.841. [DOI] [PubMed] [Google Scholar]
  • 64.Preston RA, Jy W, Jimenez JJ, Mauro LM, Horstman LL, Valle M, Aime G, Ahn YS. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension. 2003;41:211–7. doi: 10.1161/01.hyp.0000049760.15764.2d. [DOI] [PubMed] [Google Scholar]
  • 65.Sabatier F, Darmon P, Hugel B, Combes V, Sanmarco M, Velut JG, Arnoux D, Charpiot P, Freyssinet JM, Oliver C, Sampol J, Dignat-George F. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes. 2002;51:2840–5. doi: 10.2337/diabetes.51.9.2840. [DOI] [PubMed] [Google Scholar]
  • 66.Werner N, Wassmann S, Ahlers P, Kosiol S, Nickenig G. Circulating CD31+/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2006;26:112–6. doi: 10.1161/01.ATV.0000191634.13057.15. [DOI] [PubMed] [Google Scholar]
  • 67.Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52. doi: 10.1016/S0140-6736(04)17018-9. [DOI] [PubMed] [Google Scholar]
  • 68.Muller-Ehmsen J, Schmidt A, Krausgrill B, Schwinger RH, Bloch W. 2005. Role of Erythropoetin for Angiogenesis and Vasculogenesis - from Embryonic Development through Adulthood Am J Physiol Heart Circ Physiol.
  • 69.Imanishi T, Kobayashi K, Hano T, Nishio I. Effect of estrogen on differentiation and senescence in endothelial progenitor cells derived from bone marrow in spontaneously hypertensive rats. Hypertens Res. 2005;28:763–72. doi: 10.1291/hypres.28.763. [DOI] [PubMed] [Google Scholar]
  • 70.Iwakura A, Luedemann C, Shastry S, Hanley A, Kearney M, Aikawa R, Isner JM, Asahara T, Losordo DW. Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation. 2003;108:3115–21. doi: 10.1161/01.CIR.0000106906.56972.83. [DOI] [PubMed] [Google Scholar]
  • 71.Spyridopoulos I, Haendeler J, Urbich C, Brummendorf TH, Oh H, Schneider MD, Zeiher AM, Dimmeler S. Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation. 2004;110:3136–42. doi: 10.1161/01.CIR.0000142866.50300.EB. [DOI] [PubMed] [Google Scholar]
  • 72.Landmesser U, Engberding N, Bahlmann FH, Schaefer A, Wiencke A, Heineke A, Spiekermann S, Hilfiker Kleiner D, Templin C, Kotlarz D, Mueller M, Fuchs M, Hornig B, Haller H, Drexler H. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation. 2004;110:1933–9. doi: 10.1161/01.CIR.0000143232.67642.7A. [DOI] [PubMed] [Google Scholar]
  • 73.Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, Walsh K, Isner JM, Asahara T. HMG-CoA reductase inhibitor mobilizes bone marrow - derived endothelial progenitor cells. J Clin Invest. 2001;108:399–405. doi: 10.1172/JCI13131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Heissig B, Rafii S, Akiyama H, Ohki Y, Sato Y, Rafael T, Zhu Z, Hicklin DJ, Okumura K, Ogawa H, Werb Z, Hattori K. Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. J Exp Med. 2005;202:739–50. doi: 10.1084/jem.20050959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeler S. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med. 2003;9:1370–6. doi: 10.1038/nm948. [DOI] [PubMed] [Google Scholar]
  • 76.Bahlmann FH, De Groot K, Spandau JM, Landry AL, Hertel B, Duckert T, Boehm SM, Menne J, Haller H, Fliser D. Erythropoietin regulates endothelial progenitor cells. Blood. 2004;103:921–6. doi: 10.1182/blood-2003-04-1284. [DOI] [PubMed] [Google Scholar]
  • 77.Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003;102:1340–6. doi: 10.1182/blood-2003-01-0223. [DOI] [PubMed] [Google Scholar]
  • 78.Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109:625–37. doi: 10.1016/s0092-8674(02)00754-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Takamiya M, Okigaki M, Jin D, Takai S, Nozawa Y, Adachi Y, Urao N, Tateishi K, Nomura T, Zen K, Ashihara E, Miyazaki M, Tatsumi T, Takahashi T, Matsubara H. 2006. Granulocyte Colony-Stimulating Factor-mobilized circulating c-Kit+/Flk-1+ progenitor cells regenerate endothelium and inhibit neointimal hyperplasia after vascular injury Arterioscler Thromb Vasc Biol. [DOI] [PubMed]
  • 80.Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension. 2005;45:321–5. doi: 10.1161/01.HYP.0000154789.28695.ea. [DOI] [PubMed] [Google Scholar]
  • 81.Kravchenko J, Goldschmidt-Clermont PJ, Powell T, Stallard E, Akushevich I, Cuffe MS, Manton KG. Endothelial progenitor cell therapy for atherosclerosis: the philosopher's stone for an aging population. Sci Aging Knowledge Environ. 2005;2005:e18. doi: 10.1126/sageke.2005.25.pe18. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES