Derangements in adrenergic-adipokine signalling establish a neurohormonal basis for obesity-related heart failure with a preserved ejection fraction

European Journal of Heart Failure
Milton Packer

Abstract

Among patients with heart failure and a preserved ejection (HFpEF), obesity is associated with a distinct phenotype that is characterized by adiposity-driven plasma volume expansion and cardiac overfilling, which is coupled with an impairment of ventricular distensibility. These pathophysiological abnormalities may be related to the increased actions of specific adipocyte-derived signalling molecules (aldosterone, neprilysin and leptin) that work in concert with increased renal sympathetic nerve traffic and activated beta2 -adrenergic receptors to promote sodium retention, microvascular rarefaction, cardiac fibrosis and systemic inflammation. This interplay leads to striking activation of the mineralocorticoid receptor, possibly explaining why obese patients with heart failure are most likely to benefit from spironolactone and eplerenone in large-scale clinical trials. Additionally, adipocytes express and release neprilysin, which (by degrading endogenous natriuretic peptides) can further promote plasma volume expansion and cardiac fibrosis. Heightened neprilysin activity may explain the low circulating levels of natriuretic peptides in obesity, the accelerated breakdown of natriuretic peptides in HFpEF, and the cardiac decompr...Continue Reading

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Citations

Jun 13, 2018·European Journal of Heart Failure·Anne Pizard
Feb 15, 2019·European Journal of Heart Failure·Marco Metra
May 28, 2019·Circulation·Josefina RobertsonAnnika Rosengren
Jun 21, 2019·Circulation Research·Nikolaos G Frangogiannis
May 5, 2018·European Journal of Heart Failure·Marco Metra
Jan 31, 2020·ESC Heart Failure·Daniela TomasoniMarco Metra
Sep 6, 2020·International Journal of Molecular Sciences·Emma D Flood, Stephanie W Watts
Jul 4, 2020·European Journal of Heart Failure·Vishal N RaoG Michael Felker
Jan 28, 2020·Heart Failure Reviews·Ampadu O JacksonKai Yin
Nov 3, 2020·Cardiovascular Research·Nikolaos G Frangogiannis
Dec 6, 2020·ESC Heart Failure·Daniela TomasoniMarco Metra
Dec 31, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Izabela Tuleta, Nikolaos G Frangogiannis
Jul 18, 2019·JACC. Basic to Translational Science·Claudio Humeres, Nikolaos G Frangogiannis
Jul 30, 2018·Molecular Aspects of Medicine·Nikolaos G Frangogiannis
May 14, 2021·Circulation Research·Joyce N Njoroge, John R Teerlink
May 31, 2021·Heart Failure Clinics·Hidemi SorimachiBarry A Borlaug
Dec 18, 2021·ESC Heart Failure·Lorenzo StrettiDaniela Tomasoni

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