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. This evidence concerns the gene MAPK3 and hydrops fetalis.