Maternal endothelial progenitor colony-forming units with macrophage characteristics are reduced in preeclampsia.
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 (PlGF) 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.
Lin
Carol
C
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Rajakumar
Augustine
A
Plymire
Daniel A
DA
Verma
Vivek
V
Markovic
Nina
N
Hubel
Carl A
CA
D000328:Adult; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D024282:Genes, sry / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000276:immunology / Q000473:pathology; D011257:Pregnancy Proteins / Q000097:blood; D011263:Pregnancy Trimester, Third; D012243:Rhodopsin / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D012243:Rhodopsin; D040281:Vascular Endothelial Growth Factor Receptor-1