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

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Tác giả: Calum Bain, Daniela Carnevale, Lorenzo Carnevale, Raimondo Carnevale, Giuseppe D'Agostino, Slava Epelman, Stefania Fardella, Valentina Fardella, Tomasz J Guzik, Boguslaw Kapelak, Giuseppe Lembo, Francesco Mastroiacovo, Agnese Migliaccio, Tomasz P Mikołajczyk, Sara Nejat, Jacopo Pacella, Fabio Pallante, Marialuisa Perrotta, Sara Perrotta, Sarah Lena Puhl, Azzurra Zonfrilli

Ngôn ngữ: eng

Ký hiệu phân loại: 331.89041 Labor unions, labor-management bargaining and disputes

Thông tin xuất bản: United States : Immunity , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 739325

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.
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