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Maternal Endothelial Progenitor Colony-Forming Units With Macrophage Characteristics Are Reduced in Preeclampsia

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AMERICAN JOURNAL OF HYPERTENSION
卷 22, 期 9, 页码 1014-1019

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OXFORD UNIV PRESS
DOI: 10.1038/ajh.2009.101

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  1. National Institutes of Health [HD049453, MO1-RR000056, 1 UL1 RR024153-01]
  2. Pennsylvania Department of Health (Research Formula Fund).

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BACKGROUND Endothelial progenitor cells (EPCs) provide paracrine support to the vascular endothelium and may also replace damaged or senescent endothelial cells. Low numbers of endothelial progenitor colony-forming units (CFU-ECs) in culture are a predictive biomarker of vascular disease. We hypothesized that the number of CFU-ECs derived from maternal blood are decreased in women with preeclampsia compared to normal pregnancy. METHODS Primigravid women with singleton normal (n = 12) or preeclamptic (n = 12) pregnancies were studied during the third trimester. The culture assay was performed using a pre-plating step to eliminate mature endothelial cells and nonprogenitor cells; colonies per well were counted and further characterized. RESULTS Colony numbers were fourfold lower on average in preeclampsia compared to control samples (P < 0.005). A majority of the cells comprising individual colonies were positive for both endothelial (Ulex europaeus lectin staining and acetylated low-density lipoprotein (LDL) uptake) and monocyte/macrophage (CD45, CD14, CD115) characteristics. The SRY gene was detected in CFU-ECs derived from umbilical cord blood samples from male fetuses but not in CFU-ECs from peripheral blood of mothers with male fetuses. Maternal plasma concentrations of the antiangiogenic factor, soluble fms-like tyrosine kinase-1 (sFlt-1) were elevated (P < 0.0001) whereas placental growth factor (PIGF) was reduced (P < 0.01) in women with preeclampsia, but these factors did not correlate with CFU-EC counts. CONCLUSIONS CFU-ECs derived from culture of peripheral blood mononuclear cells, a correlate of cardiovascular risk in nonpregnancy populations, are rarified in women with preeclampsia compared to normal pregnancy. PCR analysis is consistent with a maternal origin of these cells. Am J Hypertens 2009; 22:1014-1019 (C) 2009 American Journal of Hypertension, Ltd.

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