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Published on: December 2, 2016
A heart-brain-spleen axis controls cardiac remodeling to hypertensive stress
Sara Perrotta1, Lorenzo Carnevale1, Marialuisa Perrotta2
1Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, Pozzilli, Italy.
Insights
Hypertensive heart disease involves a neural reflex expanding cardiac macrophages to counteract heart failure. This adaptive response, driven by placental growth factor (PlGF), is crucial for maintaining heart function under stress.
Area of Science:
- Cardiovascular Science
- Neuroimmunology
- Endocrinology
Background:
- Hypertensive heart disease (HTN-HD) is a major cause of mortality, progressing from adaptive responses to left ventricular (LV) dysfunction and heart failure (HF).
- Elevated sympathetic nervous system (SNS) activity and macrophage expansion are hallmarks of hypertensive stress, but their interaction during HTN-HD compensation is unknown.
Purpose of the Study:
- To elucidate the interaction between the sympathetic nervous system and macrophages in the compensatory phase of hypertensive heart disease.
- To identify the mechanisms by which the body adapts to hypertensive stress and prevents heart failure.
Main Methods:
- Investigated LV pressure overload models to identify neural circuits and signaling pathways involved in HTN-HD.
- Utilized splenic neuroimmune axis inhibition and cardiac resident macrophage (RM) specific receptor (neuropilin-1, NRP1) ablation to assess functional impacts.
- Correlated circulating placental growth factor (PlGF) levels with cardiac hypertrophy in humans and examined NRP1 expression in failing hearts.
Main Results:
- LV pressure overload activated a brainstem neural circuit, enhancing splenic SNS activity and inducing placental growth factor (PlGF) secretion.
- PlGF promoted the proliferation of cardiac RMs expressing its receptor, NRP1, during hypertensive stress.
- Inhibition of the neuroimmune axis or NRP1 in RMs impaired adaptive responses, leading to HF. Circulating PlGF correlated with cardiac hypertrophy, and failing hearts showed RM NRP1 expression.
Conclusions:
- A multiorgan response involving a neural reflex expands cardiac NRP1+ RMs to counteract heart failure during hypertensive stress.
- Placental growth factor (PlGF) and its receptor neuropilin-1 (NRP1) on cardiac resident macrophages (RMs) are critical for the adaptive response to hypertensive heart disease.
- This study reveals a novel neuro-immune mechanism essential for preventing heart failure progression in hypertensive heart disease.
Abstract:
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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