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

Abstract

Background - Tumor necrosis factor (TNF)-α has been implicated in the pathophysiology of congestive heart failure. A strain of transgenic mice (TNF1.6) with cardiac-specific overexpression of TNF-α develop congestive heart failure. Methods and Results - To determine the effect of anti-TNF-α 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-α 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 β-adrenergic stimulation, and it limited development of cardiac dilation. Conclusions - Blockade of TNF-α bioactivity by antibody therapy may both preserve cardiac function and partially reverse pathological changes in congestive heart failure.