Figure 3.

Brain-heart–kidney network in cardiac adaptation. Pressure overload on the left ventricle triggers a cardioprotective mechanism involving the brain, heart, and kidneys (51). Pressure overload activates sympathetic nerves to the kidneys. Within the kidneys, sympathetic nerves stimulate collecting duct epithelial cells, which activate cellular interactions leading to renal production of CSF2/GM-CSF. CSF2 is transferred to the heart via the circulation and activates cardiac tissue-resident Ly6C^lo macrophages. These activated Ly6C^lo macrophages then play a pivotal role in the adaptive response to the pressure overload. A key cardioprotective mediator produced by Ly6C^lo macrophages is amphiregulin (AREG).