Enhanced suicidal erythrocyte death in acute cardiac failure
Enhanced suicidal erythrocyte death in acute cardiac failure
复制标题
DOI：
10.1111/eci.12555
复制
发表时间：
2015-12-01
影响因子：
5.5
通讯作者：
Lang, Florian
中科院分区：
文献类型：
--
作者：
Attanasio, Philipp;Bissinger, Rosi;Lang, Florian
背景：贫血是急性心力衰竭(AHF)的常见并发症，对临床预后有负面影响。贫血的原因包括增强的胰酶作用，以细胞收缩和磷脂酰丝氨酸易位引起的细胞膜争抢为特征的自杀性红细胞死亡。触发苏醒的信号包括氧化应激、胞浆钙活性升高([Ca~(2+)](I))和神经酰胺。材料与方法取自健康志愿者(n=10)和AHF住院患者(n=22)的红细胞。结果AHF患者的血红蛋白浓度(11.5+/-0.5g/dL)和红细胞压积(35.6+/-1.2%)显著低于AHF患者(14.1+/0.4g/dL)，AHF患者网织红细胞数(2.3+/-0.3%)明显高于健康志愿者(1.1+/-0.2%)。AHF患者红细胞暴露磷脂酰丝氨酸的百分率(1.8+/-0.1%)显著高于健康志愿者(1.2+/-0.2%)。AHF患者的前向散射显著低于健康志愿者，而ROS丰度显著高于健康志愿者。在健康志愿者的红细胞中，AHF患者血浆处理24 h后，磷脂酰丝氨酸和ROS丰度显著高于健康志愿者血浆。结论AHF患者尽管网织红细胞数量增加，但仍可导致贫血，且至少部分原因是胰酶作用增强。潜在的机制包括由血浆成分造成的氧化应激。
Background A common complication of acute cardiac failure (AHF) is anaemia, which negatively influences the clinical outcome. Causes of anaemia include enhanced eryptosis, a suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation. Signalling triggering eryptosis include oxidative stress, increase of cytosolic Ca2+-activity ([Ca2+](i)) and ceramide. The present study explored whether AHF is associated with accelerated eryptosis.Materials and Methods Erythrocytes were drawn from healthy volunteers (n = 10) and patients hospitalized for AHF (n = 22). Phosphatidylserine exposure was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+](i) from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies and reactive oxygen species (ROS) abundance from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, as determined by flow cytometry.Results In AHF-patients, haemoglobin concentration (11.5 +/- 0.5 g/dL), and haematocrit (35.6 +/- 1.2%) were significantly lower than haemoglobin concentration (14.1 +/- 0.4 g/dL), and haematocrit (40.1 +/- 1.0%) in healthy volunteers, even though reticulocyte number was significantly higher in AHF patients (2.3 +/- 0.3%) than in healthy volunteers (1.1 +/- 0.2%). The percentage of erythrocytes exposing phosphatidylserine was significantly higher in AHF patients (1.8 +/- 0.1%) than in healthy volunteers (1.2 +/- 0.2%). The forward scatter was significantly lower and the ROS abundance significantly larger in AHF patients than in healthy volunteers. In erythrocytes drawn from healthy volunteers, phosphatidylserine and ROS abundance was increased to significantly higher values following a 24 h treatment with plasma from AHF patients than with plasma from healthy volunteers.Conclusion AHF leads to anaemia despite increased reticulocyte number and at least partially due to enhanced eryptosis. Underlying mechanisms include oxidative stress imposed by a plasma borne component.