Cardiac Gq Receptors and Calcineurin Activation Are Not Required for the Hypertrophic Response to Mechanical Left Ventricular Pressure Overload.
CaMKIIδ
Gq receptors
calcineurin
neurohumoral stimulation
pressure overload induced hypertrophy
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
09
12
2020
accepted:
26
01
2021
entrez:
4
3
2021
pubmed:
5
3
2021
medline:
5
3
2021
Statut:
epublish
Résumé
Gq-coupled receptors are thought to play a critical role in the induction of left ventricular hypertrophy (LVH) secondary to pressure overload, although mechano-sensitive channel activation by a variety of mechanisms has also been proposed, and the relative importance of calcineurin- and calmodulin kinase II (CaMKII)-dependent hypertrophic pathways remains controversial. To determine the mechanisms regulating the induction of LVH in response to mechanical pressure overload. Transgenic mice with cardiac-targeted inhibition of Gq-coupled receptors (GqI mice) and their non-transgenic littermates (NTL) were subjected to neurohumoral stimulation (continuous, subcutaneous angiotensin II (AngII) infusion for 14 days) or mechanical pressure overload (transverse aortic arch constriction (TAC) for 21 days) to induce LVH. Candidate signaling pathway activation was examined. As expected, LVH observed in NTL mice with AngII infusion was attenuated in heterozygous (GqI Cardiac Gq receptors and calcineurin activation are required for neurohumorally mediated LVH but not for LVH induced by mechanical pressure overload (TAC). Rather, TAC-induced LVH is associated with activation of the CaMKII-HDAC4-MEF2 pathway.
Identifiants
pubmed: 33659256
doi: 10.3389/fcell.2021.639509
pmc: PMC7917224
doi:
Types de publication
Journal Article
Langues
eng
Pagination
639509Informations de copyright
Copyright © 2021 Yu, Gong, Wu, Dai, Kesteven, Fatkin, Martinac, Graham and Feneley.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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