Anti-tumor necrosis factor-α antibody limits heart failure in a transgenic model

被引:78
作者
Kadokami, T
Frye, C
Lemster, B
Wagner, CL
Feldman, AM
McTiernan, CF
机构
[1] Univ Pittsburgh, Med Ctr Hlth Syst, Cardiovasc Inst, Pittsburgh, PA USA
[2] Centocor Inc, Malvern, PA USA
关键词
antibodies; heart failure; hormones;
D O I
10.1161/hc3501.096063
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1094 / 1097
页数:4
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