Abstract

Endothelial colony-forming cell (ECFC), a subtype of endothelial progenitor cells with high clonogenic and proliferative capacity, is present in cord and peripheral blood, participating in neovessel formation and regeneration. Cord blood ECFCs have impaired bioactivity in pregnancy complications and preterm (PT) birth. Dysfunction of cord blood ECFC is also related to complications of prematurity such as bronchopulmonary dysplasia. Although cardiovascular alterations, such as high blood pressure (BP) and left ventricular (LV) dysfunction, occur in PT subjects during adulthood, whether ECFC dysfunction beyond the neonatal period relates to such alterations is not known. OBJECTIVE: We aim in this study to assess if ECFC function relates to cardiovascular alterations in PT born adults. METHODS: Peripheral blood mononuclear cells from 30 young adults (21-28 years old) born very PT (<29 weeks gestation) and 30 at term (T, ≥37 weeks gestation) were separated by density gradient and cultured to ECFC colony formation. ECFC proliferative and angiogenic function were assessed in vitro by modified thymidine analogue (EdU) incorporation and tube formation in Matrigel. BP was measured by 24h monitor and LV mass index (g/cm 2 ) by ultrasound imaging. All analyses were performed blind; correlations were significant when p<0.05. RESULTS: The proportion of early (<15 days) and late (≥15 days) time for ECFC colony formation was different between PT and T, with a higher frequency for late growth or no colony in the PT born group. Time to colony formation inversely correlated with ECFC proliferation rate (r=-0.57, r 2 =0.32) and tube formation (r=-0.57, r 2 =0.33) in PT, which shows ECFC dysfunction in those PT subjects with late colony formation, with no significant correlations in T. Additionally, time to colony formation has positively related to systolic BP (r=0.54, r 2 =0.29) and LV mass index (r=0.49, r 2 =0.24) in PT born subjects. CONCLUSION: Our findings demonstrate, for the first time, an association between dysfunctional circulating ECFCs and cardiovascular alterations in adults born PT. We also show that ECFC dysfunction, in PT adults, significantly relates to important cardiovascular risk factors such as high BP and increased LV mass.

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