A heart-brain-spleen axis controls cardiac remodeling to hypertensive stress.

作者：S. Perrotta, L. Carnevale, Marialuisa Perrotta, F. Pallante, Tomasz P. Mikolajczyk, V. Fardella, A. Migliaccio, S. Fardella, Sara Nejat, Bogusław Kapelak, Azzurra Zonfrilli, J. Pacella, Francesco Mastroiacovo, Raimondo Carnevale, Calum C. Bain, Sarah Lena Puhl, G. D'Agostino, S. Epelman, T. J. Guzik, G. Lembo, D. Carnevale · 发表于：Immunity · 年份：2025 · DOI：10.1016/j.immuni.2025.02.013 · 被引用次数：28 · 研究领域：Medicine

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.