The hemoglobin degradation pathway in patients with preeclampsia - Fetal hemoglobin, heme, heme oxygenase-1 and hemopexin - Potential diagnostic biomarkers?
The hemoglobin degradation pathway in patients with preeclampsia - Fetal hemoglobin, heme, heme oxygenase-1 and hemopexin - Potential diagnostic biomarkers?
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DOI：
10.1016/j.preghy.2018.02.005
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发表时间：
2018-10-01
影响因子：
2.2
通讯作者：
Hansson, Stefan R.
中科院分区：
文献类型：
--
作者：
Anderson, Ulrik Dolberg;Jalmby, Maya;Hansson, Stefan R.
目的：本研究的目的是探讨母体无细胞胎儿血红蛋白和血红素如何影响子痫前期（PE）患者的清道夫酶系统血红素结合素和血红素加氧酶-1。的次要目的是评估这些蛋白质作为生物标志物的严重程度的临床表现，即高血压，在早期和晚发性PE.Material和方法：血浆样本内分娩前24小时内从135例进行了分析，89 PE和46正常妊娠。分析所有样本的无细胞胎儿血红蛋白（HbF）、血红素、血红素结合蛋白酶活性（Hx活性）、血红素结合蛋白浓度（Hx）和血红素加氧酶1浓度（HO-1）。结果：PE血浆中HbF（p = 0.01）和血红素（p = 0.01）水平显著高于正常妊娠血浆，而Hx活性（p = 0.02）、Hx（p < 0.0001）和HO-1（p = 0.03）显著低于正常妊娠血浆。Hx活性与舒张压呈显著负相关（p = 0.04）。HO-1浓度与收缩压和舒张压均呈显著负相关（p = 0.01和p = 0.003）。ROC曲线分析显示，这些生物标志物的联合检测率为84%，在10%的假阳性率。结论：增加母亲血浆血红素和HbF水平在PE与HO-1和血红素结合蛋白的蛋白水平下降，以及降低血红素结合蛋白的活性。通过测量清道夫蛋白Hx和Hb降解系统中的蛋白质的消耗，可以获得关于疾病动力学的临床信息。
Objective: The aim of this study was to investigate how maternal cell-free fetal hemoglobin and heme impact the scavenger enzyme systems Hemopexin and Heme Oxygenase-1 in patients with preeclampsia (PE). The secondary aims were to evaluate these proteins as biomarkers for severity of the clinical manifestation i.e. hypertension, in early- and late onset PE.Material and methods: Plasma samples taken within the last 24 h before delivery from 135 patients were analyzed, 89 PE and 46 normal pregnancies. All samples were analyzed for cell-free fetal hemoglobin (HbF), heme, hemopexin enzymatic activity (Hx activity), hemopexin concentration (Hx), and heme oxygenase 1 concentration (HO-1). Logistic regression analysis with ROC-curve analysis was performed to evaluate the possible use as biomarkers for preeclampsia.Results: There were significantly higher levels of HbF (p = 0.01) and heme (0.01) but significantly lower Hx activity (p = 0.02), Hx (p < 0.0001) and HO-1 (p = 0.03) in PE plasma as compared to plasma of normal pregnancies. The Hx activity was significantly inversely correlated (p = 0.04) to the diastolic blood pressure. The HO-1 concentration was significantly inversely correlated to both the systolic and diastolic blood pressure (p = 0.01 and p = 0.003). ROC-curve analysis showed a combined detection rate for these biomarkers of 84% at 10% false positive rate.Conclusions: Increased maternal plasma levels of heme and HbF in PE are associated with decreased HO-1 and hemopexin protein levels as well as reduced hemopexin activity. By measuring the consumption of the scavenger protein Hx, and the proteins in the Hb degradation system, clinical information about the dynamics of the disease can be obtained.