Laboratory of Cardiovascular Science, National Institute on Aging, Intramural Research Program, NIH, Baltimore, Maryland 21224, USA.
J Hypertens. 2010 Feb;28(2):361-6. doi: 10.1097/HJH.0b013e328333226c.
Preeclampsia is a major cause of maternal and fetal mortality, and its pathogenesis is not fully understood. Endogenous digitalis-like cardiotonic steroids (CTS) have been implicated in the pathophysiology of preeclampsia; this is illustrated by clinical observations that Digibind, a therapeutic digoxin antibody fragment which binds CTS, lowers blood pressure and reverses Na/K-ATPase inhibition in patients with preeclampsia. Recently we reported that plasma levels of marinobufagenin (MBG), a bufadienolide vasoconstrictor CTS, are increased four-fold in patients with severe preeclampsia.
In the present study, we compared levels of MBG in normal and preeclamptic placentae, as well as the interactions of Digibind and antibodies against MBG and ouabain with material purified from preeclamptic placentae using high-performance liquid chromatography (HPLC).
Levels of endogenous MBG, but not that of endogenous ouabain, exhibited a four-fold elevation in preeclamptic placentae vs. normal placentae (13.6 +/- 2.5 and 48.6 +/- 7.0 nmoles/g tissue; P < 0.01). The elution time of endogenous placental MBG-like immunoreactive material from reverse-phase HPLC column was identical to that of authentic MBG. A competitive immunoassay based on Digibind exhibited reactivity to HPLC fractions having retention times similar to that seen with MBG and other bufadienolides, but not to ouabain-like immunoreactive material.
Our results suggest that elevated levels of endogenous bufadienolide CTS represent a potential target for immunoneutralization in patients with preeclampsia.
子痫前期是孕产妇和胎儿死亡的主要原因，其发病机制尚未完全阐明。内源性洋地黄类强心甾（CTS）与子痫前期的病理生理学有关；这可以通过临床观察得到说明，即 Digibind，一种与 CTS 结合的治疗性洋地黄抗体片段，可降低血压并逆转子痫前期患者的 Na/K-ATP 酶抑制。最近我们报道，严重子痫前期患者的血浆中海洋 Bufagenin（MBG）水平增加了四倍，MBG 是一种 Bufadienolide 血管收缩性 CTS。
在本研究中，我们比较了正常和子痫前期胎盘组织中 MBG 的水平，以及 Digibind 以及针对 MBG 和哇巴因的抗体与从子痫前期胎盘组织中纯化的物质之间的相互作用，使用高效液相色谱法（HPLC）。
内源性 MBG 水平（而非内源性哇巴因水平）在子痫前期胎盘组织中升高了四倍，与正常胎盘组织相比（分别为 13.6 +/- 2.5 和 48.6 +/- 7.0nmoles/g 组织；P < 0.01）。从反相 HPLC 柱洗脱的内源性胎盘 MBG 免疫反应性物质的洗脱时间与真实 MBG 相同。基于 Digibind 的竞争性免疫测定法对保留时间与 MBG 和其他 Bufadienolides 相似的 HPLC 馏分表现出反应性，但对哇巴因免疫反应性物质无反应性。
我们的结果表明，内源性 Bufadienolide CTS 水平升高可能代表子痫前期患者免疫中和的潜在靶标。
