Abstract
ContextEndothelial dysfunction is a primary feature of preeclampsia, a pregnancy complication associated with an increased future cardiovascular risk for mother and offspring. Endothelial colony forming cells (ECFC) are endothelial progenitor cells that participate in vasculogenesis and endothelial repair.ObjectiveWe hypothesized that the number and functional properties of fetal cord blood-derived ECFCs are reduced in preeclampsia compared to uncomplicated pregnancy (controls), and asked if adverse effects of preeclampsia on ECFC function are reversed by 1,25 (OH)2 vitamin D3.Design, Setting, PatientsThis was a nested, case-control study. Forty women with uncomplicated pregnancy and 33 women with PE were recruited at Magee-Womens Hospital (USA) or at Hannover Medical School (Germany).Main Outcome MeasuresTime to ECFC colony appearance in culture, and number of colonies formed, were determined. Functional abilities of ECFCs were assessed in vitro by tubule formation in Matrigel assay, migration, and proliferation. ECFC function was tested in the presence or absence of 1,25 (OH)2 vitamin D3, and after vitamin D receptor (VDR) or VEGF signaling blockade.ResultsThe number of cord ECFC colonies was lower (P = 0.04) in preeclampsia compared to controls. ECFCs from preeclampsia showed reduced proliferation (P<0.0001), formed fewer tubules (P = 0.02), and migrated less (P = 0.049) than control. Vitamin D3 significantly improved preeclampsia ECFC functional properties. VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3.ConclusionFetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional. Vitamin D3 had rescuing effects. This may have implications for the increased cardiovascular risk associated with preeclampsia.
Highlights
Impaired placentation and maternal endothelial dysfunction are principal features of the pregnancy syndrome preeclampsia (PE) that affects 3–7% of all pregnancies [1,2]
The number of cord Endothelial colony forming cells (ECFC) colonies was lower (P = 0.04) in preeclampsia compared to controls
Fetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional
Summary
Impaired placentation and maternal endothelial dysfunction are principal features of the pregnancy syndrome preeclampsia (PE) that affects 3–7% of all pregnancies [1,2]. EPC numbers and function inversely correlate with the risk of developing cardiovascular disease [7]. Based on these characteristics EPCs have been intensively studied in the context of cardiovascular risk [8]. Endothelial colony forming cells (ECFCs) are a well-defined subpopulation of EPCs. Unlike other EPC sub-types, they are directly involved in vasculogenesis and vascularization by populating the endothelial surface. Unlike other EPC sub-types, they are directly involved in vasculogenesis and vascularization by populating the endothelial surface They are involved in feto-placental vasculogenesis [9], which is disturbed in women with PE [10]. There is evidence that maternal and fetal (umbilical cord) circulating EPCs of hematopoietic lineage are reduced in number and function during PE [11,12,13], data on ECFCs are presently rare
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