A multiorgan neural reflex involving the brainstem and spleen enhances placental growth factor secretion to expand cardiac NRP1+ resident macrophages and counteract heart failure in hypertensive stress.
Does a heart-brain-spleen axis control cardiac remodeling to hypertensive stress?
Identified a multiorgan neural reflex involving the spleen and brainstem that expands cardiac NRP1+ resident macrophages to counteract heart failure during hypertensive stress.
Hypertensive heart disease (HTN-HD) meaningfully contributes to hypertension morbidity and mortality. Initially established as an adaptive response, HTN-HD progresses toward worsening of left ventricule (LV) function and heart failure (HF). Hypertensive stress elevates sympathetic nervous system (SNS) activity, a negative clinical predictor, and expands macrophages. How they interact in the compensatory phase of HTN-HD is unclear. We report that LV pressure overload recruited a brainstem neural circuit to enhance splenic SNS and induce placental growth factor (PlGF) secretion. During hypertensive stress, PlGF drove the proliferation of self-renewing cardiac resident macrophages (RMs) expressing its receptor neuropilin-1 (NRP1). Inhibition of the splenic neuroimmune axis or ablation of NRP1 in RM hindered the adaptive response to hypertensive stress, leading to HF. In humans, circulating PlGF correlated with cardiac hypertrophy, and failing hearts expressed NRP1 in RMs. Here, we discovered a multiorgan response driving a neural reflex to expand cardiac NRP1+ RM and counteract HF.
Perrotta et al. (Fri,) conducted a other in Hypertensive heart disease. LV pressure overload / Splenic neuroimmune axis inhibition was evaluated on Cardiac remodeling and heart failure progression. A multiorgan neural reflex involving the brainstem and spleen enhances placental growth factor secretion to expand cardiac NRP1+ resident macrophages and counteract heart failure in hypertensive stress.