Levels of circulating endothelial cells and circulating progenitor cells in normal and intrauterine growth restriction pregnancies

Introduction: Circulating endothelial progenitor cells (EPCs) are bone marrow-derived mononuclear cells involved in adult vasculogenesis that are reduced in patients with cardiovascular risk factors. Circulating endothelial cells (CECs) are mature endothelial cells detached from the vascular intimal layer whose increased numbers are taken to imply vascular damage. Deficient remodelling of the uterine vessels in the first trimester of pregnancy is a cause of placental insufficiency, leading to clinical maternal or fetal disorders in later pregnancy as intrauterine growth restriction (IUGR). In this study we investigated posssible alterations in EPC and CEC balance in pregnancies complicated by IUGR. Materials and methods: Maternal pheripheral blood was obtained from pregnancy complicated by idiopathic IUGR (n=12) in the third trimester and in normal pregnancy (n=22) at the same gestational age. EPCs and CECs were counted in blood samples by flow cytometry. EPCs were identified as either CD45dim/CD34+/KDR+ or CD45dim/CD34+/KDR+/CD133+cells; CECs as CD45dim/CD31+/CD146+ cells. EPC:CEC ratio was also calculated, as a potential marker of imbalance between endothelial damage and repair. Results: Women in IUGR pregnancy had a reduced number of EPCs compared with normal pregnancy. This reduction was evident when EPCs were identified as either CD45dim/CD34+/KDR+ (mean±s.e.: 570±123 cells/ml vs 1022±124; p<0.02) or CD45dim/CD34+/KDR+/CD133+ cells (353±115 vs 525±83; p=0.08). On the contrary, women in IUGR pregnancy showed higher CEC levels (1246±387 vs 525±144; p<0.05). As a consequence, women in IUGR pregnancy had lower EPC:CEC ratios (CD45dim/CD34+/KDR+ EPCs: 0.81±0.27 vs 2.76±0.80, p<0.01; CD45dim/CD34+/ KDR+/CD133+ EPCs: 0.49±0.24 vs 1.21±0.40, p<0.05). Conclusion: The altered levels of EPCs, CECs and their ratios observed in pregnancy complicated by IUGR are strongly indicative of an imbalance between endothelial damage and repair that may be related to the dysfunctional processes occurring in the placental vascular endothelium.