期刊论文详细信息
Journal of Angiogenesis Research
The angiogenic gene profile of circulating endothelial progenitor cells from ischemic stroke patients
Anna Rosell1  Joan Montaner1  Babette Barbash Weksler4  Pierre-Olivier Couraud3  Ignacio A Romero2  Marc Ribó1  Israel Fernandez-Cadenas1  Mar Hernández-Guillamon1  Míriam Navarro-Sobrino1 
[1] Neurovascular Research Laboratory and Neurovascular Unit. Neurology and Medicine Department, Universitat Autònoma de Barcelona. Vall d’Hebron Research Institute of Vall d’Hebron Hospital, Pg Vall d’Hebron 119-129, Barcelona, 08035, Spain;Department of Life Sciences, The Open University, Milton Keynes, UK;Division of Hematology and Medical Oncology, Institut Cochin, Université Paris Descartes, Paris, France;Weill Medical College of Cornell University, New York, NY, USA
关键词: Vasculogenesis;    Gene expression;    Endothelial progenitor cells;    Angiogenesis;    Ischemic stroke;   
Others  :  801756
DOI  :  10.1186/2045-824X-5-3
 received in 2012-10-02, accepted in 2013-01-29,  发布年份 2013
PDF
【 摘 要 】

Background

The identification of circulating endothelial progenitor cells (EPCs) has introduced new possibilities for cell-based treatments for stroke. We tested the angiogenic gene expression of outgrowth endothelial cells (OECs), an EPC subtype capable to shape vessel structures.

Methods

OECs (at colony or mature stages) from ischemic stroke patients (n=8) were characterized using the RT2 ProfilerTM human angiogenesis PCR Array, and human microvascular endothelial cells (hCMEC/D3) were used as an expression reference of endothelial cells.

Results

Colony-OECs showed higher expression of CCL2, ID3, IGF-1, MMP9, TGFBR1, TNFAIP2, TNF and TGFB1. However, BAI-1, NRP2, THBS1, MMP2 and VEGFC expression was increased in mature-OECs (p<0.05). ID3 (p=0.008) and TGFBR1 (p=0.03) genes remained significantly overexpressed in colony-OECs compared to mature-OECs or hCMEC/D3. MMP9 levels were significantly increased in colony-OECs (p=0.025) compared to mature-OECs. Moreover, MMP-2, VEGF-C, THBS1 and NRP-2 gene expression was also significantly increased in mature-OECs compared to hCMEC/D3 (p<0.05). Some of these genes were positively validated by RT-PCR.

Conclusion

Our study shows that OECs from stroke patients present higher levels of pro-angiogenic factors at early stages, decreasing in mature OECs when they become more similar to mature microvascular endothelial cells.

【 授权许可】

   
2013 Navarro-Sobrino et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140708012509522.pdf 1186KB PDF download
Figure 2. 26KB Image download
Figure 1. 116KB Image download
【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】
  • [1]Rafii S, Lyden D: Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 2003, 9:702-712.
  • [2]Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, Krasich R, Temm CJ, Prchal JT, Ingram DA: Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 2007, 109:1801-1809.
  • [3]Reinisch A, Hofmann NA, Obenauf AC, Kashofer K, Rohde E, Schallmoser K, Flicker K, Lanzer G, Linkesch W, Speicher MR, Strunk D: Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo. Blood 2009, 113:6716-6725.
  • [4]Navarro-Sobrino M, Rosell A, Hernandez-Guillamon M, Penalba A, Ribó M, Alvarez-Sabín J, Montaner J: Mobilization, endothelial differentiation and functional capacity of endothelial progenitor cells after ischemic stroke. Microvasc Res 2010, 80:317-323.
  • [5]Weksler BB, Subileau EA, Perrière N, Charneau P, Holloway K, Leveque M, Tricoire-Leignel H, Nicotra A, Bourdoulous S, Turowski P, Male DK, Roux F, Greenwood J, Romero IA, Couraud PO: Blood–brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J 2005, 19:1872-1874.
  • [6]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)). Method 2001, 25:402-408.
  • [7]Avouac J, Cagnard N, Distler JH, Schoindre Y, Ruiz B, Couraud PO, Uzan G, Boileau C, Chiocchia G, Allanore Y: Insights into the pathogenesis of systemic sclerosis based on gene expression profile of progenitor-derived endotelial cells. Arthritis Rheum 2011, 63:3552-3562.
  • [8]Igreja C, Fragoso R, Caiado F, Clode N, Henriques A, Camargo L, Reis EM, Dias S: Detailed molecular characterization of cord blood-derived endotelial progenitors. Exp Hematol 2008, 36:193-203.
  • [9]Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett NR, Crystal RG, Moore MA, Hajjar KA, Manova K, Benezra R, Rafii S: Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001, 7:1194-1201.
  • [10]Thum T, Hoeber S, Froese S, Klink I, Stichtenoth DO, Galuppo P, Jakob M, Tsikas D, Anker SD, Poole-Wilson PA, Borlak J, Ertl G, Bauersachs J: Age-dependent impairment of endothelial progenitor cells is corrected by growth-hormone-mediated increase of insulin-like growth-factor-1. Circ Res 2007, 100:434-443.
  • [11]Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, Zeiher AM, Dimmeler S: Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol 2005, 39:733-742.
  • [12]Huang PH, Chen YH, Wang CH, Chen JS, Tsai HY, Lin FY, Lo WY, Wu TC, Sata M, Chen JW, Lin SJ: Matrix metalloproteinase-9 is essential for ischemia-induced neovascularization by modulating bone marrow-derived endothelial progenitor cells. Arterioscler Thromb Vasc Biol 2009, 29:1179-1184.
  • [13]Moonen JR, O'Neill CL, Sweeney M, Guduric-Fuchs J, Gardiner TA, Simpson DA, Stitt AW: Endothelial progenitor cells give rise to pro-angiogenic smooth muscle-like progeny. Cardiovasc Res 2010, 86:506-515.
  • [14]Wyler von Ballmoos M, Yang Z, Völzmann J, Baumgartner I, Kalka CD: Endothelial progenitor cells induce a phenotype shift in differentiated endothelial cells towards PDGF/PDGFRβ axis-mediated angiogenesis. PLoS One 2010, 5:e14107.
  • [15]Medina RJ, O'Neill CL, Sweeney M, Guduric-Fuchs J, Gardiner TA, Simpson DA, Stitt AW: Molecular analysis of endothelial progenitor cell (EPC) subtypes reveals two distinct cell populations with different identities. BMC Med Genomics 2010, 3:18. BioMed Central Full Text
  • [16]Ohta T, Kikuta K, Imamura H, Takagi Y, Nishimura M, Arakawa Y, Hashimoto N, Nozaki K: Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats. Neurosurgery 2006, 59:679-686.
  • [17]Fan Y, Shen F, Frenzel T, Zhu W, Ye J, Liu J, Chen Y, Su H, Young WL, Yang GY: Endothelial progenitor cell transplantation improves long-term stroke outcome in mice. Ann Neurol 2010, 67:488-497.
  • [18]Moubarik C, Guillet B, Youssef B, Codaccioni JL, Piercecchi MD, Sabatier F, Lionel P, Dou L, Foucault-Bertaud A, Velly L, Dignat-George F, Pisano P: Transplanted late outgrowth endothelial progenitor cells as cell therapy product for stroke. Stem Cell Rev 2011, 7:208-220.
  • [19]Tura O, Skinner EM, Robin Barclay G, Samuel K, Gallagher RC, Brittan M, Hadoke PW, Newby DE, Turner ML, Mills NL: Late outgrowth endothelial cells resemble mature endothelial cells and are not derived from bone marrow. Stem Cells 2012. Epub ahead of print
  • [20]Bulut D, Albrecht N, Imöhl M, Günesdogan B, Bulut-Streich N, Börgel J, Hanefeld C, Krieg M, Mügge A: Hormonal status modulates circulating endotelial progenitor cells. Clin Res Cardiol 2007, 96:258-263.
  文献评价指标  
  下载次数:15次 浏览次数:19次