Lin Carol, Rajakumar Augustine, Plymire Daniel A, Verma Vivek, Markovic Nina, Hubel Carl A
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Am J Hypertens. 2009 Sep;22(9):1014-9. doi: 10.1038/ajh.2009.101. Epub 2009 Jun 4.
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.
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.
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.
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.
内皮祖细胞（EPCs）为血管内皮提供旁分泌支持，还可能替代受损或衰老的内皮细胞。培养中内皮祖细胞集落形成单位（CFU-ECs）数量少是血管疾病的预测生物标志物。我们假设，与正常妊娠相比，子痫前期女性母体血液中衍生的CFU-ECs数量减少。
在妊娠晚期研究了初产妇单胎正常妊娠（n = 12）或子痫前期妊娠（n = 12）的情况。使用预铺板步骤进行培养测定以消除成熟内皮细胞和非祖细胞；对每孔的集落进行计数并进一步表征。
与对照样本相比，子痫前期的集落数量平均低四倍（P < 0.005）。构成单个集落的大多数细胞对内皮（荆豆凝集素染色和乙酰化低密度脂蛋白（LDL）摄取）和单核细胞/巨噬细胞（CD45、CD14、CD115）特征均呈阳性。在来自男性胎儿脐带血样本的CFU-ECs中检测到SRY基因，但在怀有男性胎儿母亲的外周血CFU-ECs中未检测到。子痫前期女性母体血浆中抗血管生成因子可溶性fms样酪氨酸激酶-1（sFlt-1）浓度升高（P < 0.0001），而胎盘生长因子（PlGF）降低（P < 0.01），但这些因素与CFU-EC计数无关。
来自外周血单个核细胞培养的CFU-ECs，在非妊娠人群中是心血管风险的一个相关指标，与正常妊娠相比，子痫前期女性中该细胞数量稀少。PCR分析与这些细胞的母体来源一致。
