Using a rat model of HF induced by myocardial infarction, we found that genetic knockdown of TACE expression in the PVN or inhibition of TACE activity in the brain reduces TNF-α levels along with reduced activation of the NF-κB and ERK1/2 signaling, and decreases expression of inflammatory mediators and sympathetic activity, leading to improvements in cardiac remodeling and dysfunction in the development of HF. The gene discussed is MAPK3; the disease is myocardial infarction.