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  • Review Article
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Neuroimmune crosstalk in the pathophysiology of hypertension

Nature Reviews Cardiology volume 16, pages 476–490 (2019)Cite this article

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Abstract

Hypertension is an important risk factor for cardiovascular morbidity and mortality and for events such as myocardial infarction, stroke, heart failure and chronic kidney disease and is a major determinant of disability-adjusted life-years. Despite the importance of hypertension, the pathogenesis of essential hypertension, which involves the complex interaction of several mechanisms, is still poorly understood. Evidence suggests that interplay between bone marrow, microglia and immune mediators underlies the development of arterial hypertension, in particular through mechanisms involving cytokines and peptides, such as neuropeptide Y, substance P, angiotensin II and angiotensin-(1–7). Chronic psychological stress also seems to have a role in increasing the risk of hypertension, probably through the activation of neuroimmune pathways. In this Review, we summarize the available data on the possible role of neuroimmune crosstalk in the origin and maintenance of arterial hypertension and discuss the implications of this crosstalk for recovery and rehabilitation after cardiac and cerebral injuries.

Key points

  • A proposed interplay between the bone marrow, microglia and immune mediators could underlie the development of arterial hypertension.

  • Brain microglia activation is a hallmark of neuroinflammation in hypertension; the bone marrow contributes to hypertension by increasing the extravasation of peripheral inflammatory cells into the brain.

  • Chronic psychological stress increases the risk of hypertension through a mechanism involving the bone marrow and sympathetic nervous system.

  • Cytokines, neuropeptides and peptides including neuropeptide Y, substance P, angiotensin II and angiotensin-(1–7) seem to act as messengers between immunity, the central nervous system and the cardiovascular system to regulate blood pressure homeostasis.

  • Genome-wide association studies have identified links between three pairs of genes related to inflammation and diastolic blood pressure and between BDNF (encoding a neurotrophic factor implicated in neuropeptide Y modulation) and hypertension.

  • Clinical evidence shows that neuroimmune factors are involved in changes in the regulation of the cardiovascular system underlying arterial hypertension.

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Fig. 1: Proposed interaction between the bone marrow, microglia and immune mediators in arterial hypertension.
Fig. 2: Interactions between ANGII, ANG-(1–7), NPY, substance P and the immune system in hypertension.
Fig. 3: Proposed link between stress-related hypertension and neuroinflammation.

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Acknowledgements

The authors are grateful to J. Eugenio Ochoa (Department of Cardiovascular Neural and Metabolic Sciences, San Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy) for his valuable and constructive suggestions and to P. Wijnmaalen (IRCCS Istituto Auxologico Italiano, Milan, Italy) for help with creating the figures.

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Authors and Affiliations

  1. Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy

    Laura Calvillo, Lia Crotti & Gianfranco Parati

  2. Departamento de Química Biológica, IQUIFIB-CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Mariela M. Gironacci

  3. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

    Lia Crotti & Gianfranco Parati

  4. Istituto Auxologico Italiano, IRCCS, Immunology Research Laboratory, Milan, Italy

    Pier Luigi Meroni

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L.C. researched the data for the article. All the authors discussed its content, wrote the manuscript and reviewed and edited it before submission. G.P. conceived the idea of the paper and coordinated the revisions.

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Calvillo, L., Gironacci, M.M., Crotti, L. et al. Neuroimmune crosstalk in the pathophysiology of hypertension. Nat Rev Cardiol 16, 476–490 (2019). https://doi.org/10.1038/s41569-019-0178-1

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