Sainte-Justine University Hospital Research Center, Université de Montréal, Quebec, Canada.
Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'Île-de-Montréal, Hôpital du Sacré-Cœur de Montréal Research Center, Université de Montréal, Quebec, Canada.
J Am Heart Assoc. 2018 Jul 9;7(14):e009720. doi: 10.1161/JAHA.118.009720.
Preterm birth is linked to cardiovascular risks and diseases. Endothelial progenitor cells play a critical role in vascular development and repair. Cord blood endothelial progenitor cells of preterm-born infants, especially endothelial colony-forming cells (ECFC), show enhanced susceptibility to prematurity-related pro-oxidant stress. Whether ECFC dysfunction is present in adulthood following preterm birth is unknown.
This cross-sectional observational study includes 55 preterm-born (≤29 gestational weeks) young adults (18-29 years old, 38% male) and 55 sex- and age-matched full-term controls. ECFC were isolated from peripheral blood; cell proliferative and vascular cord formation capacities were assessed in vitro. Daytime systolic blood pressure was higher, whereas glucose tolerance and body mass index were lower in preterm-born subjects. ECFC colonies grew in culture for 62% of full-term- and 58% of preterm-born participants. Preterm-born participants have formed ECFC colonies later in culture and have reduced proliferation compared with controls. Only in preterm-born individuals, we observed that the later the ECFC colony grows in culture, the worse was overall ECFC function. In addition, in preterms, elevated systolic blood pressure significantly correlated with reduced ECFC proliferation (r=-0.463; =0.030) and numbers of branches formed on matrigel (r=-0.443; =0.039). In preterm-born subjects, bronchopulmonary dysplasia was associated with impaired ECFC function, whereas exposure to antenatal steroids related to better ECFC function.
This study is the first to examine ECFC in preterm-born adults and to demonstrate ECFC dysfunction compared with full-term controls. In the preterm-born group, ECFC dysfunction was associated with bronchopulmonary dysplasia, the major prematurity-related neonatal morbidity, and with increased systolic blood pressure into adulthood.
早产与心血管风险和疾病有关。内皮祖细胞在血管发育和修复中起着关键作用。早产儿的脐带血内皮祖细胞，特别是内皮集落形成细胞（ECFC），对与早产相关的促氧化剂应激的敏感性增强。早产儿出生后是否存在 ECFC 功能障碍尚不清楚。
本横断面观察性研究纳入了 55 名（≤29 孕周）早产儿（18-29 岁，38%为男性）和 55 名性别和年龄匹配的足月对照组。从外周血中分离 ECFC；评估体外细胞增殖和血管形成能力。早产儿的日间收缩压较高，而糖耐量和体重指数较低。ECFC 集落在培养中生长的比例为足月组的 62%和早产儿组的 58%。早产儿组 ECFC 集落培养时间较晚，增殖能力较对照组降低。只有在早产儿中，我们观察到 ECFC 集落在培养中生长越晚，整体 ECFC 功能越差。此外，在早产儿中，收缩压升高与 ECFC 增殖减少（r=-0.463；p=0.030）和基质胶上分支形成数量减少（r=-0.443；p=0.039）显著相关。在早产儿中，支气管肺发育不良与 ECFC 功能障碍有关，而产前皮质类固醇暴露与 ECFC 功能改善有关。
本研究首次检测了早产儿成年后 ECFC 的功能，并与足月对照组进行了比较，发现早产儿 ECFC 功能障碍。在早产儿组中，ECFC 功能障碍与支气管肺发育不良有关，这是与早产相关的主要新生儿发病率，并且与成年后收缩压升高有关。
