目的：探讨低体重早产儿的内皮祖细胞（endothelial progenitor cells, EPCs）血管生成能力及调控机制。方法：收集15例低体重早产儿（胎龄小于37周且体重小于 2.5 kg）和19例对照足月儿（胎龄大于37周且体重大于等于2.5 kg）的脐带血,于诱导分化前用流式细胞仪检测EPCs（CD34+/CD133+/VEGFR2+）的数量。分离培养后,检测EPCs克隆形成时间、克隆形成能力、细胞增殖能力和小管形成能力。用蛋白印迹法检测EPCs中血管内皮钙粘蛋白（vascular endothelial cadherin,VE-cadherin）和血管内皮生长因子受体2（vascular endothelial growth factor receptors 2,VEGFR2）的表达情况。结果：与足月儿相比（0.003%±0.002%）,低体重早产儿脐带血中的EPCs百分比（0.0026%±0.0025%）并无变化,但EPCs克隆形成时间推迟（18 d比12 d）,克隆形成能力、细胞增殖能力及小管形成能力均较足月儿下降（P均<0.05）。蛋白印迹法检测结果显示,低体重早产儿脐带血EPCs中的VE-cadherin和VEGFR2表达降低。结论：低体重早产儿的EPCs血管生成能力受损,可能与EPCs中血管内皮特异性标志物VE-cadherin、VEGFR2表达降低有关。
Objective: To investigate the angiogenic properties of cord blood endothelial progenitor cells (EPCs) in low birth weight(LBW) preterm infants. Methods: Venous umbilical cord blood was collected from 19 cases of full-term neonates with normal weight and 15 LBW neonates. The relative number of cord blood EPCs (CD34+/CD133+/VEGFR2+) from LBW preterm and full-term neonates was counted by ?ow cytometry. The angiogenic properties of cord blood EPCs were evaluated for the time for clone formation, clone forming ability and capacity to proliferate and formtubes in vitro. Results: There was no difference in the relative number of cord blood EPCs between LBW preterm and full-term neonates. Compared with EPCs of full-term neonates, the time for clone formation of EPCs was delayed in LBW, while clone forming ability and capacity to proliferate and form tubes were decreased. The expressions of VEGFR2 and VE-cadherin of EPCs in LBW were significantly reduced. Conclusions: Angiogenic properties of EPCs are impaired in LBW preterm infants, and this may be due to the decreased expression of VE-cadherin and VEGFR2.
[1] Irving RJ, Belton NR, Elton RA, et al.Adult cardiovascular risk factors in premature babies[J]. Lancet,2000,355(9221):2135-2136.
[2] Siewert-Delle A, Ljungman S.The impact of birth weight and gestational age on blood pressure in adult life: a population-based study of 49-year-old men[J]. Am J Hypertens,1998,11(8 Pt 1):946-953.
[3] Bonamy AK, Bendito A, Martin H, et al.Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls[J]. Pediatr Res,2005, 58(5):845-849.
[4] Asahara T, Murohara T, Sullivan A, et al.Isolation of putative progenitor endothelial cells for angiogenesis[J]. Science,1997,275(5302):964-967.
[5] Tauzin L, Rossi P, Giusano B, et al.Characteristics of arterial stiffness in very low birth weight premature infants[J]. Pediatr Res,2006,60(5):592-596.
[6] Ligi I, Simoncini S, Tellier E, et al.A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants[J]. Blood,2011,118(6):1699-1709.
[7] Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors[J]. Nat Med,2003,9(6):669-676.
[8] Ligi I, Simoncini S, Tellier E, et al.Altered angiogenesis in low birth weight individuals: a role for anti-angiogenic circulating factors[J]. J Matern Fetal Neonatal Med,2014, 27(3):233-238.
[9] Carmeliet P, Lampugnani MG, Moons L, et al.Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis[J]. Cell,1999,98(2):147-157.
[10] Calera MR, Venkatakrishnan A, Kazlauskas A.VE-cadherin increases the half-life of VEGF receptor 2[J]. Exp Cell Res,2004,300(1):248-256.
