Targeting blockade of nuclear factor-κB in the hypothalamus paraventricular nucleus to prevent cardiac sympathetic hyperinnervation post myocardial infarction.

Nuclear factor-κB (NF-κB) is considered to be a master inflammation regulator and involved in sympathetic neural hyperinnervation after myocardial infarction (MI). Paraventricular nucleus (PVN), acts as the sympathetic outflow tract, has been proven to play an important role during MI, but whether NF-κB pathway in the PVN participates in the pathogenesis of sympathetic sprouting and reinnervation after MI are unclear.MI was induced by coronary artery ligation, NF-κB was activated and interleukin-1β (IL-1β) and nerve growth factor (NGF) levels were increased in the PVN after MI. Lipopolysaccharide (LPS) stimulation also can activate NF-κB pathway, followed by increasing the expressions of IL-1β and NGF in the PVN, once combining with gevokizumab (an IL-1β inhibitor) significantly reduced the expressions of IL-1β and NGF, but could not affect the NF-κB expression in the PVN. Furthermore, micro-injection of the NF-κB inhibitor pyrrolidine dithiocarbamate into PVN in MI rats, significantly inhibited the activation of NF-κB and further reduced the expression of IL-1β and NGF in the PVN, finally blunting sympathetic hyperinnervation in the heart, moreover, the blockade of NF-κB in the PVN reduced the incidence of ventricular arrhythmias (VAs).Cardiac nerve sprouting after MI is associated in part with NF-κB activation in the PVN, and IL-1β is involved in the process. Targeting blockade of NF-κB in the PVN may be a potential approach to ameliorate sympathetic hyperinnervation and reduce the incidence of VAs after MI.