Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure.
Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure.
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DOI：
10.1038/ajh.2012.17
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发表时间：
2012-06
影响因子：
3.2
通讯作者：
Bagrov, Alexei Y.
中科院分区：
文献类型：
--
作者：
Haller, Steven T.;Kennedy, David J.;Shidyak, Amjad;Budny, George V.;Malhotra, Deepak;Fedorova, Olga V.;Shapiro, Joseph I.;Bagrov, Alexei Y.
关键词：
强心类固醇（CTS）与尿毒症心肌病的病理生理学有关。在本研究中，我们测试了针对蟾蜍二烯内酯 CTS 的单克隆抗体 (mAb) 是否能减轻部分肾切除 (PNx) 大鼠的心脏肥大和纤维化。在 PNx 大鼠中，我们比较了 3E9 抗 MBG mAb 和 Digibind（一种亲和纯化的地高辛抗体）对术后 4 周后血压以及心脏肥大和纤维化的影响。在 PNx 大鼠中，血浆 MBG 水平升高四倍与高血压、心脏羰化蛋白水平升高、心脏肥大、心脏核转录因子 Fli-1（胶原蛋白合成负调节因子 Fli-1）表达减少以及胶原蛋白 1 水平升高相关。对 PNx 大鼠进行单次腹腔内注射 3E9 mAb，可使血压降低 59 mmHg，持续 7 天，并显着降低心脏重量和心脏氧化应激水平，增加 Fli-1 的表达，并减少心脏纤维化。 Digibind 的效果与 3E9 mAb 相似，但不太明显。在实验性慢性肾功能衰竭中，MBG 水平升高会导致高血压，并通过抑制 Fli-1 诱导心脏纤维化，Fli-1 是潜在的治疗靶点。
Cardiotonic steroids (CTS) are implicated in pathophysiology of uremic cardiomyopathy. In the present study, we tested whether a monoclonal antibody (mAb) against the bufadienolide CTS, marinobufagenin (MBG), alleviates cardiac hypertrophy and fibrosis in partially nephrectomized (PNx) rats. In PNx rats, we compared the effects of 3E9 anti-MBG mAb and of Digibind, an affinity-purified digoxin antibody, on blood pressure and cardiac hypertrophy and fibrosis following 4 weeks after the surgery. In PNx rats, a four-fold elevation in plasma MBG levels was associated with hypertension, increased cardiac levels of carbonylated protein, cardiac hypertrophy, a reduction in cardiac expression of a nuclear transcription factor which is a negative regulator of collagen synthesis, Fli-1, and an increase in the levels of collagen-1. A single intraperitoneal administration of 3E9 mAb to PNx rats reduced blood pressure by 59 mmHg for 7 days and produced a significant reduction in cardiac weight and cardiac levels of oxidative stress, an increase in the expression of Fli-1, and a reduction in cardiac fibrosis. The effects of Digibind were similar to those of 3E9 mAb, but were less pronounced. In experimental chronic renal failure, elevated levels of MBG contribute to hypertension and induce cardiac fibrosis via suppression of Fli-1, representing a potential target for therapy.
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影响因子：
8.3
作者：
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通讯作者：
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