抗肿瘤坏死因子-α抗体在转基因模型中可限制心力衰竭。
Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic model.
作者信息
Kadokami T, Frye C, Lemster B, Wagner C L, Feldman A M, McTiernan C F
机构信息
Cardiovascular Institute of the University of Pittsburgh Medical Center Health System, Pittsburgh, PA, USA.
出版信息
Circulation. 2001 Sep 4;104(10):1094-7. doi: 10.1161/hc3501.096063.
BACKGROUND
- Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of congestive heart failure. A strain of transgenic mice (TNF1.6) with cardiac-specific overexpression of TNF-alpha develop congestive heart failure.
METHODS AND RESULTS
To determine the effect of anti-TNF-alpha therapy in this model, we studied 3 groups: TNF1.6 mice treated with saline, wild-type mice treated with saline, and TNF1.6 mice treated with TNF-alpha neutralizing antibody (cV1q) from 6 to 12 weeks of age. We used echocardiography to compare cardiac hypertrophy, function, and catecholamine response at 12 weeks of age versus baseline (6 weeks). cV1q treatment did not limit cardiac hypertrophy, but it significantly improved basal fractional shortening and responsiveness to beta-adrenergic stimulation, and it limited development of cardiac dilation.
CONCLUSIONS
Blockade of TNF-alpha bioactivity by antibody therapy may both preserve cardiac function and partially reverse pathological changes in congestive heart failure.
背景
肿瘤坏死因子（TNF）-α与充血性心力衰竭的病理生理机制有关。一种心脏特异性过度表达TNF-α的转基因小鼠品系（TNF1.6）会发生充血性心力衰竭。
方法与结果
为了确定抗TNF-α治疗在该模型中的效果，我们研究了3组小鼠：6至12周龄用生理盐水治疗的TNF1.6小鼠、用生理盐水治疗的野生型小鼠以及用TNF-α中和抗体（cV1q）治疗的TNF1.6小鼠。我们使用超声心动图比较了12周龄时与基线（6周）时的心脏肥大、功能和儿茶酚胺反应。cV1q治疗并未限制心脏肥大，但它显著改善了基础缩短分数和对β-肾上腺素能刺激的反应性，并且限制了心脏扩张的发展。
结论
通过抗体治疗阻断TNF-α生物活性可能既保留心脏功能又部分逆转充血性心力衰竭的病理变化。
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