未破裂颅内动脉瘤患者外周血内皮祖细胞数量的研究
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摘要
目的研究未破裂颅内动脉瘤与外周血中内皮祖细胞(endothelial progenitor cells,EPCs)数量的关系。方法选择未破裂颅内动脉瘤患者24例和正常对照16例,用密度梯度离心法从外周血获取单个核细胞,接种在人纤维连接蛋白覆盖的培养瓶,经加入血管内皮生长因子165和碱性成纤维细胞生长因子的EGM-2MV培养基诱导培养。动态观察其增殖过程。对培养14天后贴壁的EPCs细的进行计数、鉴定和分析。激光共聚焦显微镜下吞噬FITC标记的荆豆凝集素和结合Dil标记的acLDL双染色阳性细胞为成熟的EPCs；并用流式细胞仪检测细胞表面CD34、CD133和VEGFR-2抗原,测定细胞表面抗原CD34、CD133和VEGFR-2三抗阳性的细胞数以及比例。分析比较两组外周血中内皮祖细胞的数量差异,并在病例组进行相关因素研究,分析动脉瘤最大径同外周血EPCs细胞数关系。结果一、EPCs的数量检测中：颅内动脉瘤患者外周血EPCs数量较对照组明显减少(5.1±1.5)×104比(43.3±29.8)×104, (P<0.05),流式细胞仪分析结果显示CD34+/CD133+/VEGFR-2+的细胞数比例(6.94%±1.78%比17.83%±3.41%,P<0.05)有显著差异。二、基本资料中：颅内动脉瘤患者甘油三酯(1.86±1.37) mmol/L比健康对照组(1.58±0.98) mmol/L明显升高(P<0.05)；颅内动脉瘤患者胆固醇(3.85±1.67) mmol/L比健康对照组(3.67±1.26) mmol/L明显升高(P<0.05)；颅内动脉瘤患者HDL (1.08±0.26) mmol/L比健康对照组(1.96±0.64)mmol/L显著降低(P<0.05)。三、24例病例组动脉瘤最大径(5.4±3.4)mm。病例组的动脉瘤最大径与病例组EPCs计数无统计相关性(P>0.05)
结论未破裂颅内动脉瘤患者外周血EPCs的数量与健康人比明显降低。EPCs在未破裂颅内动脉瘤中的作用值得进一步研究探讨。
Objective:To investigate the morphology, growth and counts of endothelial progenitor cells in peripheral blood of patients with unruptured intracranial aneurysms(UIAs). Method: Twenty-four patients of UIA Group and 16 of Control Group were analysed. Mononuclear cells from peripheral blood were harvested by density gradient centrifugation. Then the cells were seeded onto a bottle which was precoated with human fibronectin and cultured in medium EGM-2MV supplemented with vascular endothelial growth factor-165 and basic fibroblast growth factor. The proliferation course of EPCs was observed. After fourteen-day culturing, the adherent cells were identified through morphology observation and the colony count was performed under microscope. The biological functions of adherent cells were examined with laser confocal microscope. The double dyeing positivity, that is adsorption of Ulex europaeus agglutinin-1 (UEA-1) labeled by fluorescein isothiocyanate (FITC) and Dil-acLDL internalization, were considered as EPCs. Flow cytometry was used to count the EPCs by identifying three cell surface markers:CD34, CD 133 and VEGFR-2. The number of circulating endothelial progenitor cells between the two groups was compared, and the correlation of the maximum aneurysm diameter and the number of circulating EPCs was analyzed.
Results:1、The counts of endothelial progenitor cells in peripheral blood were significantly lower in patientswith UIAs [(5.1±1.5)×104] than that in control group [(43.3±29.8)×104] (P<0.05). Moreover, the portion of CD34+/CD133+/VEGFR-2+cells were significantly decreased in patients with UIAs than that in controls (6.94%±1.78% vs 17.83%±3.41%,P<0.05).2, The value of triglycerides in patients with UIA [(1.86±1.37) mmol/L] was significantly higher than that of control group [(1.58±0.98) mmol/L], (P<0.05); The cholesterol is significantly higher in UIA [(3.85±1.67) mmol/L] than that of healthy control group [(3.67±1.26) mmol/L],(P<0.05); HDL significantly less in intracranial aneurysms is [(1.08±0.26) mmol/L] than that of healthy control group [(1.96±0.64) mmol/L], (P<0.05).3、A total of 24 patients were recruited in UIAs group, the maximum aneurysm diameters were (5.4±3.4) mm. No significant correlation between the maximum aneurysm diameters and EPCs counts in patient group has been shown (P> 0.05)
Conclusion:The results shew that the number of EPCs in UIAs group was significantly lower than that of control group. Further study on the role of EPCs in UIAs may be promising in future.
结论未破裂颅内动脉瘤患者外周血EPCs的数量与健康人比明显降低。EPCs在未破裂颅内动脉瘤中的作用值得进一步研究探讨。
Objective:To investigate the morphology, growth and counts of endothelial progenitor cells in peripheral blood of patients with unruptured intracranial aneurysms(UIAs). Method: Twenty-four patients of UIA Group and 16 of Control Group were analysed. Mononuclear cells from peripheral blood were harvested by density gradient centrifugation. Then the cells were seeded onto a bottle which was precoated with human fibronectin and cultured in medium EGM-2MV supplemented with vascular endothelial growth factor-165 and basic fibroblast growth factor. The proliferation course of EPCs was observed. After fourteen-day culturing, the adherent cells were identified through morphology observation and the colony count was performed under microscope. The biological functions of adherent cells were examined with laser confocal microscope. The double dyeing positivity, that is adsorption of Ulex europaeus agglutinin-1 (UEA-1) labeled by fluorescein isothiocyanate (FITC) and Dil-acLDL internalization, were considered as EPCs. Flow cytometry was used to count the EPCs by identifying three cell surface markers:CD34, CD 133 and VEGFR-2. The number of circulating endothelial progenitor cells between the two groups was compared, and the correlation of the maximum aneurysm diameter and the number of circulating EPCs was analyzed.
Results:1、The counts of endothelial progenitor cells in peripheral blood were significantly lower in patientswith UIAs [(5.1±1.5)×104] than that in control group [(43.3±29.8)×104] (P<0.05). Moreover, the portion of CD34+/CD133+/VEGFR-2+cells were significantly decreased in patients with UIAs than that in controls (6.94%±1.78% vs 17.83%±3.41%,P<0.05).2, The value of triglycerides in patients with UIA [(1.86±1.37) mmol/L] was significantly higher than that of control group [(1.58±0.98) mmol/L], (P<0.05); The cholesterol is significantly higher in UIA [(3.85±1.67) mmol/L] than that of healthy control group [(3.67±1.26) mmol/L],(P<0.05); HDL significantly less in intracranial aneurysms is [(1.08±0.26) mmol/L] than that of healthy control group [(1.96±0.64) mmol/L], (P<0.05).3、A total of 24 patients were recruited in UIAs group, the maximum aneurysm diameters were (5.4±3.4) mm. No significant correlation between the maximum aneurysm diameters and EPCs counts in patient group has been shown (P> 0.05)
Conclusion:The results shew that the number of EPCs in UIAs group was significantly lower than that of control group. Further study on the role of EPCs in UIAs may be promising in future.
引文
1 Hazama F, Kataoka H, Yamada E, Kayembe K, Hashimoto N, Kojima M, Kim C. Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study. Am J Pathol. 1986:124:399-404
2 Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R. Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke.1999:30:1396-1401
3 Mizutani T, Kojima H. Clinicopathological features of non-atherosclerotic cerebral arterial trunk aneurysms. Neuropathology.2000;20:91-97
4 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
5 Sun B, Zhang S, Ni C, Zhang D, Liu Y, Zhang W, Zhao X, Zhao C, Shi M. Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow. Stem Cells Dev.2005; 14:292-298
6 Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, Pratt RE, Mulligan RC, Dzau VJ. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts:Implications for cell-based vascular therapy. Circulation.2003;108:2710-2715
7 Jamous MA, Nagahiro S, Kitazato KT, Tamura T, Aziz HA, Shono M, Satoh K. Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation:Experimental study in rats. J Neurosurg.2007; 107:405-411
8 Werner N, Priller J, Laufs U, Endres M. Bohm M, Dirnagl U, Nickenig G. Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation:Effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler Thromb Vasc Biol. 2002;22:1567-1572
9 Sabatier F, Camoin-Jau L, Anfosso F, Sampol J, Dignat-George F. Circulating endothelial cells, microparticles and progenitors:Key players towards the definition of vascular competence. J Cell Mol Med.2009;13:454-471
1 Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R. Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke.1999;30:1396-1401
2 Hazama F, Kataoka H, Yamada E, Kayembe K, Hashimoto N, Kojima M, Kim C. Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study. Am J Pathol. 1986;124:399-404
3 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
4 Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, Pratt RE. Mulligan RC, Dzau VJ. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts:Implications for cell-based vascular therapy. Circulation.2003; 108:2710-2715
5 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;24:2295-2302
6 He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke.2004;35:2378-2384
7 Sabatier F. Camoin-Jau L, Anfosso F, Sampol J, Dignat-George F. Circulating endothelial cells, microparticles and progenitors:Key players towards the definition of vascular competence. J Cell Mol Med.2009;13:454-471
8 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
9 Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond). 2004; 107:273-280
10 Zhang Q, Yin H, Liu P, Zhang H, She M. Essential role of hdl on endothelial progenitor cell proliferation with pi3k/akt/cyclin dl as the signal pathway. Exp Biol Med (Maywood).235:1082-1092
11 Oliveras A. Soler MJ. Martinez-Estrada OM, Vazquez S. Marco-Feliu D, Vila JS, Vilaro S, Lloveras J. Endothelial progenitor cells are reduced in refractory hypertension. J Hum Hypertens. 2008;22:183-190
12 Pirro M, Schillaci G, Menecali C, Bagaglia F, Paltriccia R, Vaudo G, Mannarino MR. Mannarino E. Reduced number of circulating endothelial progenitors and hoxa9 expression in cd34+ cells of hypertensive patients. J Hypertens.2007;25:2093-2099
13 Taylor CL, Yuan Z, Selman WR, Ratcheson RA, Rimm AA. Cerebral arterial aneurysm formation and rupture in 20.767 elderly patients:Hypertension and other risk factors. J Neurosurg.1995;83:812-819
14 Rafat N, Beck G, Pena-Tapia PG, Schmiedek P. Vajkoczy P. Increased levels of circulating endothelial progenitor cells in patients with moyamoya disease. Stroke.2009;40:432-438
15 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:El-7
16 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;53:195-199
17 Egan CG, Lavery R, Caporali F, Fondelli C, Laghi-Pasini F, Dotta F, Sorrentino V. Generalised reduction of putative endothelial progenitors and cxcr4-positive peripheral blood cells in type 2 diabetes. Diabetologia.2008;51:1296-1305
18 Park KW, Hwang KK, Cho HJ, Hur J, Yang HM, Yoon CH, Kang HJ. Oh BH, Park YB, Kim HS. Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine il-8 secretion from monocytes. Clin Chim Acta.2008; 388:156-166
19 Spiel AO, Mayr FB, Leitner JM, Firbas C, Sieghart W, Jilma B. Simvastatin and rosuvastatin mobilize endothelial progenitor cells but do not prevent their acute decrease during systemic inflammation. Thromb Res.2008;123:108-113
20 Laufs 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; 109:220-226
21 Walther C, Adams V, Bothur I, Drechsler K, Fikenzer S, Sonnabend M. Bublitz B, Korner A, Erbs S, Busse M, Schuler G. Increasing physical education in high school students:Effects on concentration of circulating endothelial progenitor cells. Eur J Cardiovasc Prev Rehabil. 2008; 15:416-422
22 Mano R. Ishida A, Ohya Y, Todoriki H, Takishita S. Dietary intervention with okinawan vegetables increased circulating endothelial progenitor cells in healthy young women. Atherosclerosis.2009:204:544-548
23 Tao J, Wang Y, Yang Z, Tu C, Xu MG, Wang JM. Circulating endothelial progenitor cell deficiency contributes to impaired arterial elasticity in persons of advancing age. J Hum Hypertens.2006;20:490-495
24 Michaud SE. Dussault S, Haddad P, Groleau J, Rivard A. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis.2006; 187:423-432
25 Kosierkiewicz TA, Factor SM, Dickson DW. Immunocytochemical studies of atherosclerotic lesions of cerebral berry aneurysms. J Neuropathol Exp Neurol.1994;53:399-406
26 Chironi G, Walch L, Pernollet MG, Gariepy J, Levenson J, Rendu F, Simon A. Decreased number of circulating cd34+kdr+ cells in asymptomatic subjects with preclinical atherosclerosis. Atherosclerosis.2007; 191:115-120
27 Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E. Menegolo M, Grego F. Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006:26:2140-2146
28 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; 106:2781-2786
29 Timmermans F, Plum J, Yoder MC, Ingram DA, Vandekerckhove B, Case J. Endothelial progenitor cells:Identity defined? J Cell Mol Med.2009; 13:87-102
1 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
2 Eggennann J, Kliche S. Jarmy G, Hoffmann K, Mayr-Beyrle U, Debatin KM, Waltenberger J, Beltinger C. Endothelial progenitor cell culture and differentiation in vitro:A methodological comparison using human umbilical cord blood. Cardiovasc Res.2003;58:478-486
3 Quirici N. Soligo D, Caneva L, Servida F, Bossolasco P, Deliliers GL. Differentiation and expansion of endothelial cells from human bone marrow cd133(+) cells. Br J Haematol. 2001;115:186-194
4 Hirashima M, Kataoka H, Nishikawa S. Matsuyoshi N. Maturation of embryonic stem cells into endothelial cells in an in vitro model of vasculogenesis. Blood.1999;93:1253-1263
5 Liu P, Zhou B, Gu D, Zhang L, Han Z. Endothelial progenitor cell therapy in atherosclerosis:A double-edged sword? Ageing Res Rev.2009;8:83-93
6 Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: Towards marker and target identification. Nat Rev Cancer.2006;6:835-845
7 Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA. Rafii S. Expression of vegfr-2 and ac133 by circulating human cd34(+) cells identifies a population of functional endothelial precursors. Blood.2000;95:952-958
8 Kim JH, Jung JH. Phi JH. Kang HS, Kim JE, Chae JH, Kim SJ, Kim YH, Kim YY, Cho BK, Wang KC, Kim SK. Decreased level and defective function of circulating endothelial progenitor cells in children with moyamoya disease. J Neurosci Res.88:510-518
9 Jung KH, Chu K, Lee ST. Park HK, Kim DH, Kim JH, Bahn JJ, Song EC, Kim M. Lee SK. Roh JK. Circulating endothelial progenitor cells as a pathogenetic marker of moyamoya disease. J Cereb Blood Flow Metab.2008;28:1795-1803
10 Rafat N. Beck G, Pena-Tapia PG, Schmiedek P, Vajkoczy P. Increased levels of circulating endothelial progenitor cells in patients with moyamoya disease. Stroke.2009;40:432-438
11 Janic B. Arbab AS. The role and therapeutic potential of endothelial progenitor cells in tumor neovascularization. Scientific WorldJournal.10:1088-1099
12 Laufs 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;109:220-226
13 Walther C, Adams V, Bothur I, Drechsler K, Fikenzer S. Sonnabend M. Bublitz B. Korner A, Erbs S, Busse M, Schuler G. Increasing physical education in high school students:Effects on concentration of circulating endothelial progenitor cells. Eur J Cardiovasc Prev Rehabil. 2008;15:416-422
14 Mano R, Ishida A, Ohya Y, Todoriki H, Takishita S. Dietary intervention with okinawan vegetables increased circulating endothelial progenitor cells in healthy young women. Atherosclerosis.2009;204:544-548
15 Park KW, Hwang KK, Cho HJ, Hur J, Yang HM, Yoon CH, Kang HJ, Oh BH, Park YB, Kim HS. Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine il-8 secretion from monocytes. Clin Chim Acta.2008;388:156-166
16 Spiel AO, Mayr FB, Leitner JM, Firbas C, Sieghart W, Jilma B. Simvastatin and rosuvastatin mobilize endothelial progenitor cells but do not prevent their acute decrease during systemic inflammation. Thromb Res.2008; 123:108-113
17 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
18 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;53:195-199
19 Egan CG, Lavery R, Caporali F, Fondelli C, Laghi-Pasini F, Dotta F. Sorrentino V. Generalised reduction of putative endothelial progenitors and cxcr4-positive peripheral blood cells in type 2 diabetes. Diabetologia.2008;51:1296-1305
20 Hamed S, Brenner B, Roguin A. Nitric oxide:A key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2. Cardiovasc Res.
21 Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond). 2004; 107:273-280
22 Oliveras A, Soler MJ, Martinez-Estrada OM, Vazquez S. Marco-Feliu D, Vila JS, Vilaro S. Lloveras J. Endothelial progenitor cells are reduced in refractory hypertension. J Hum Hypertens. 2008;22:183-190
23 Tao J, Wang Y, Yang Z, Tu C, Xu MG, Wang JM. Circulating endothelial progenitor cell deficiency contributes to impaired arterial elasticity in persons of advancing age. J Hum Hypertens.2006;20:490-495
24 Michaud SE, Dussault S, Haddad P, Groleau J, Rivard A. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis.2006;187:423-432
25 Puls M. Schroeter MR, Steier J, Stijohann L, Hasenfuss G, Konstantinides S, Schafer K. Effect of smoking cessation on the number and adhesive properties of early outgrowth endothelial progenitor cells. Int J Cardiol.
26 Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, Liew CC, Pratt RE, Dzau VJ. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation.2004; 109:1769-1775
27 Davidoff AM, Ng CY, Brown P, Leary MA, Spurbeck WW. Zhou J, Horwitz E, Vanin EF, Nienhuis AW. Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin Cancer Res. 2001;7:2870-2879
28 Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction:Final one-year results of the topcare-ami trial. J Am Coll Cardiol.2004;44:1690-1699
29 Beeres SL, Bax JJ, Dibbets-Schneider P, Stokkel MP, Fibbe WE, van der Wall EE, Schalij MJ, Atsma DE. Sustained effect of autologous bone marrow mononuclear cell injection in patients with refractory angina pectoris and chronic myocardial ischemia:Twelve-month follow-up results. Am Heart J.2006; 152:684 e611-686
30 Zhang ZG, Zhang L, Jiang Q, Chopp M. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res.2002; 90:284-288
31 Taguchi A, Matsuyama T, Moriwaki H, Hayashi T, Hayashida K, Nagatsuka K, Todo K, Mori K, Stern DM. Soma T, Naritomi H. Circulating cd34-positive cells provide an index of cerebrovascular function. Circulation.2004; 109:2972-2975
32 Huang WJ. Xiao FY, Zhang HQ, Lin YN, Cai XL, Zhou H, Lin J, Yang DY. [effects of endothelial progenitor cells and endothelial outgrowth cells in repair of injured carotid vessel:A comparative study with rabbits]. Zhonghua Yi Xue Za Zhi.2007;87:3143-31
2 Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R. Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke.1999:30:1396-1401
3 Mizutani T, Kojima H. Clinicopathological features of non-atherosclerotic cerebral arterial trunk aneurysms. Neuropathology.2000;20:91-97
4 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
5 Sun B, Zhang S, Ni C, Zhang D, Liu Y, Zhang W, Zhao X, Zhao C, Shi M. Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow. Stem Cells Dev.2005; 14:292-298
6 Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, Pratt RE, Mulligan RC, Dzau VJ. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts:Implications for cell-based vascular therapy. Circulation.2003;108:2710-2715
7 Jamous MA, Nagahiro S, Kitazato KT, Tamura T, Aziz HA, Shono M, Satoh K. Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation:Experimental study in rats. J Neurosurg.2007; 107:405-411
8 Werner N, Priller J, Laufs U, Endres M. Bohm M, Dirnagl U, Nickenig G. Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation:Effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler Thromb Vasc Biol. 2002;22:1567-1572
9 Sabatier F, Camoin-Jau L, Anfosso F, Sampol J, Dignat-George F. Circulating endothelial cells, microparticles and progenitors:Key players towards the definition of vascular competence. J Cell Mol Med.2009;13:454-471
1 Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R. Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke.1999;30:1396-1401
2 Hazama F, Kataoka H, Yamada E, Kayembe K, Hashimoto N, Kojima M, Kim C. Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study. Am J Pathol. 1986;124:399-404
3 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
4 Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, Pratt RE. Mulligan RC, Dzau VJ. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts:Implications for cell-based vascular therapy. Circulation.2003; 108:2710-2715
5 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;24:2295-2302
6 He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke.2004;35:2378-2384
7 Sabatier F. Camoin-Jau L, Anfosso F, Sampol J, Dignat-George F. Circulating endothelial cells, microparticles and progenitors:Key players towards the definition of vascular competence. J Cell Mol Med.2009;13:454-471
8 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
9 Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond). 2004; 107:273-280
10 Zhang Q, Yin H, Liu P, Zhang H, She M. Essential role of hdl on endothelial progenitor cell proliferation with pi3k/akt/cyclin dl as the signal pathway. Exp Biol Med (Maywood).235:1082-1092
11 Oliveras A. Soler MJ. Martinez-Estrada OM, Vazquez S. Marco-Feliu D, Vila JS, Vilaro S, Lloveras J. Endothelial progenitor cells are reduced in refractory hypertension. J Hum Hypertens. 2008;22:183-190
12 Pirro M, Schillaci G, Menecali C, Bagaglia F, Paltriccia R, Vaudo G, Mannarino MR. Mannarino E. Reduced number of circulating endothelial progenitors and hoxa9 expression in cd34+ cells of hypertensive patients. J Hypertens.2007;25:2093-2099
13 Taylor CL, Yuan Z, Selman WR, Ratcheson RA, Rimm AA. Cerebral arterial aneurysm formation and rupture in 20.767 elderly patients:Hypertension and other risk factors. J Neurosurg.1995;83:812-819
14 Rafat N, Beck G, Pena-Tapia PG, Schmiedek P. Vajkoczy P. Increased levels of circulating endothelial progenitor cells in patients with moyamoya disease. Stroke.2009;40:432-438
15 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:El-7
16 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;53:195-199
17 Egan CG, Lavery R, Caporali F, Fondelli C, Laghi-Pasini F, Dotta F, Sorrentino V. Generalised reduction of putative endothelial progenitors and cxcr4-positive peripheral blood cells in type 2 diabetes. Diabetologia.2008;51:1296-1305
18 Park KW, Hwang KK, Cho HJ, Hur J, Yang HM, Yoon CH, Kang HJ. Oh BH, Park YB, Kim HS. Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine il-8 secretion from monocytes. Clin Chim Acta.2008; 388:156-166
19 Spiel AO, Mayr FB, Leitner JM, Firbas C, Sieghart W, Jilma B. Simvastatin and rosuvastatin mobilize endothelial progenitor cells but do not prevent their acute decrease during systemic inflammation. Thromb Res.2008;123:108-113
20 Laufs 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; 109:220-226
21 Walther C, Adams V, Bothur I, Drechsler K, Fikenzer S, Sonnabend M. Bublitz B, Korner A, Erbs S, Busse M, Schuler G. Increasing physical education in high school students:Effects on concentration of circulating endothelial progenitor cells. Eur J Cardiovasc Prev Rehabil. 2008; 15:416-422
22 Mano R. Ishida A, Ohya Y, Todoriki H, Takishita S. Dietary intervention with okinawan vegetables increased circulating endothelial progenitor cells in healthy young women. Atherosclerosis.2009:204:544-548
23 Tao J, Wang Y, Yang Z, Tu C, Xu MG, Wang JM. Circulating endothelial progenitor cell deficiency contributes to impaired arterial elasticity in persons of advancing age. J Hum Hypertens.2006;20:490-495
24 Michaud SE. Dussault S, Haddad P, Groleau J, Rivard A. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis.2006; 187:423-432
25 Kosierkiewicz TA, Factor SM, Dickson DW. Immunocytochemical studies of atherosclerotic lesions of cerebral berry aneurysms. J Neuropathol Exp Neurol.1994;53:399-406
26 Chironi G, Walch L, Pernollet MG, Gariepy J, Levenson J, Rendu F, Simon A. Decreased number of circulating cd34+kdr+ cells in asymptomatic subjects with preclinical atherosclerosis. Atherosclerosis.2007; 191:115-120
27 Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E. Menegolo M, Grego F. Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006:26:2140-2146
28 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; 106:2781-2786
29 Timmermans F, Plum J, Yoder MC, Ingram DA, Vandekerckhove B, Case J. Endothelial progenitor cells:Identity defined? J Cell Mol Med.2009; 13:87-102
1 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
2 Eggennann J, Kliche S. Jarmy G, Hoffmann K, Mayr-Beyrle U, Debatin KM, Waltenberger J, Beltinger C. Endothelial progenitor cell culture and differentiation in vitro:A methodological comparison using human umbilical cord blood. Cardiovasc Res.2003;58:478-486
3 Quirici N. Soligo D, Caneva L, Servida F, Bossolasco P, Deliliers GL. Differentiation and expansion of endothelial cells from human bone marrow cd133(+) cells. Br J Haematol. 2001;115:186-194
4 Hirashima M, Kataoka H, Nishikawa S. Matsuyoshi N. Maturation of embryonic stem cells into endothelial cells in an in vitro model of vasculogenesis. Blood.1999;93:1253-1263
5 Liu P, Zhou B, Gu D, Zhang L, Han Z. Endothelial progenitor cell therapy in atherosclerosis:A double-edged sword? Ageing Res Rev.2009;8:83-93
6 Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: Towards marker and target identification. Nat Rev Cancer.2006;6:835-845
7 Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA. Rafii S. Expression of vegfr-2 and ac133 by circulating human cd34(+) cells identifies a population of functional endothelial precursors. Blood.2000;95:952-958
8 Kim JH, Jung JH. Phi JH. Kang HS, Kim JE, Chae JH, Kim SJ, Kim YH, Kim YY, Cho BK, Wang KC, Kim SK. Decreased level and defective function of circulating endothelial progenitor cells in children with moyamoya disease. J Neurosci Res.88:510-518
9 Jung KH, Chu K, Lee ST. Park HK, Kim DH, Kim JH, Bahn JJ, Song EC, Kim M. Lee SK. Roh JK. Circulating endothelial progenitor cells as a pathogenetic marker of moyamoya disease. J Cereb Blood Flow Metab.2008;28:1795-1803
10 Rafat N. Beck G, Pena-Tapia PG, Schmiedek P, Vajkoczy P. Increased levels of circulating endothelial progenitor cells in patients with moyamoya disease. Stroke.2009;40:432-438
11 Janic B. Arbab AS. The role and therapeutic potential of endothelial progenitor cells in tumor neovascularization. Scientific WorldJournal.10:1088-1099
12 Laufs 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;109:220-226
13 Walther C, Adams V, Bothur I, Drechsler K, Fikenzer S. Sonnabend M. Bublitz B. Korner A, Erbs S, Busse M, Schuler G. Increasing physical education in high school students:Effects on concentration of circulating endothelial progenitor cells. Eur J Cardiovasc Prev Rehabil. 2008;15:416-422
14 Mano R, Ishida A, Ohya Y, Todoriki H, Takishita S. Dietary intervention with okinawan vegetables increased circulating endothelial progenitor cells in healthy young women. Atherosclerosis.2009;204:544-548
15 Park KW, Hwang KK, Cho HJ, Hur J, Yang HM, Yoon CH, Kang HJ, Oh BH, Park YB, Kim HS. Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine il-8 secretion from monocytes. Clin Chim Acta.2008;388:156-166
16 Spiel AO, Mayr FB, Leitner JM, Firbas C, Sieghart W, Jilma B. Simvastatin and rosuvastatin mobilize endothelial progenitor cells but do not prevent their acute decrease during systemic inflammation. Thromb Res.2008; 123:108-113
17 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
18 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;53:195-199
19 Egan CG, Lavery R, Caporali F, Fondelli C, Laghi-Pasini F, Dotta F. Sorrentino V. Generalised reduction of putative endothelial progenitors and cxcr4-positive peripheral blood cells in type 2 diabetes. Diabetologia.2008;51:1296-1305
20 Hamed S, Brenner B, Roguin A. Nitric oxide:A key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2. Cardiovasc Res.
21 Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond). 2004; 107:273-280
22 Oliveras A, Soler MJ, Martinez-Estrada OM, Vazquez S. Marco-Feliu D, Vila JS, Vilaro S. Lloveras J. Endothelial progenitor cells are reduced in refractory hypertension. J Hum Hypertens. 2008;22:183-190
23 Tao J, Wang Y, Yang Z, Tu C, Xu MG, Wang JM. Circulating endothelial progenitor cell deficiency contributes to impaired arterial elasticity in persons of advancing age. J Hum Hypertens.2006;20:490-495
24 Michaud SE, Dussault S, Haddad P, Groleau J, Rivard A. Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis.2006;187:423-432
25 Puls M. Schroeter MR, Steier J, Stijohann L, Hasenfuss G, Konstantinides S, Schafer K. Effect of smoking cessation on the number and adhesive properties of early outgrowth endothelial progenitor cells. Int J Cardiol.
26 Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, Liew CC, Pratt RE, Dzau VJ. Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation.2004; 109:1769-1775
27 Davidoff AM, Ng CY, Brown P, Leary MA, Spurbeck WW. Zhou J, Horwitz E, Vanin EF, Nienhuis AW. Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin Cancer Res. 2001;7:2870-2879
28 Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction:Final one-year results of the topcare-ami trial. J Am Coll Cardiol.2004;44:1690-1699
29 Beeres SL, Bax JJ, Dibbets-Schneider P, Stokkel MP, Fibbe WE, van der Wall EE, Schalij MJ, Atsma DE. Sustained effect of autologous bone marrow mononuclear cell injection in patients with refractory angina pectoris and chronic myocardial ischemia:Twelve-month follow-up results. Am Heart J.2006; 152:684 e611-686
30 Zhang ZG, Zhang L, Jiang Q, Chopp M. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res.2002; 90:284-288
31 Taguchi A, Matsuyama T, Moriwaki H, Hayashi T, Hayashida K, Nagatsuka K, Todo K, Mori K, Stern DM. Soma T, Naritomi H. Circulating cd34-positive cells provide an index of cerebrovascular function. Circulation.2004; 109:2972-2975
32 Huang WJ. Xiao FY, Zhang HQ, Lin YN, Cai XL, Zhou H, Lin J, Yang DY. [effects of endothelial progenitor cells and endothelial outgrowth cells in repair of injured carotid vessel:A comparative study with rabbits]. Zhonghua Yi Xue Za Zhi.2007;87:3143-31