Nur77 protects against adverse cardiac remodelling by limiting neuropeptide Y signalling in the sympathoadrenal-cardiac axis

Cardiovascular Research
Lejla MedzikovicVivian de Waard

Abstract

Cardiac remodelling and heart failure are promoted by persistent sympathetic activity. We recently reported that nuclear receptor Nur77 may protect against sympathetic agonist-induced cardiac remodelling in mice. The sympathetic co-transmitter neuropeptide Y (NPY) is co-released with catecholamines and is a known cardiac modulator and predictor of heart failure mortality. Recently, transcriptome analyses revealed NPY as a putative target of Nur77. In this study, we assess whether Nur77 modulates adverse cardiac remodelling via NPY signalling. Nur77 represses NPY expression in the PC12 adrenal chromaffin cell line. Accordingly, NPY levels are higher in adrenal gland, plasma, and heart from Nur77-KO compared to wild-type mice. Conditioned medium from Nur77-silenced chromaffin cells and serum from Nur77-KO mice induce marked hypertrophy in cultured neonatal rat cardiomyocytes, which is inhibited by the NPY type 1 receptor (NPY1R) antagonist BIBO3304. In cardiomyocytes from Nur77-KO mice, intracellular Ca2+ is increased partially via the NPY1R. This is independent from elevated circulating NPY since cardiomyocyte-specific Nur77-deficient mice (CM-KO) do not have elevated circulating NPY, but do exhibit BIBO3304-sensitive, increased...Continue Reading

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Citations

Feb 11, 2021·International Journal of Molecular Sciences·Lejla MedzikovicVivian de Waard
Mar 20, 2021·Stem Cell Research & Therapy·Mika J VälimäkiHeikki Ruskoaho
Apr 6, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Guangyong HuangWenbo Yang
Aug 8, 2021·International Journal of Molecular Sciences·Ana ParedesMercedes Ricote

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