Assessing the role of extracellular signal-regulated kinases 1 and 2 in volume overload-induced cardiac remodelling.
Animals
Apoptosis
Arteriovenous Shunt, Surgical
/ methods
Atrial Natriuretic Factor
/ metabolism
Heart Failure
/ metabolism
Humans
Hypertrophy, Left Ventricular
/ genetics
Male
Mice
Mice, Inbred C57BL
/ genetics
Mitogen-Activated Protein Kinase 1
/ metabolism
Mitogen-Activated Protein Kinase 3
/ metabolism
Myocytes, Cardiac
/ metabolism
Phosphorylation
/ physiology
RNA, Messenger
/ metabolism
Signal Transduction
/ physiology
Ventricular Remodeling
/ genetics
Aortocaval fistula model
Cardiac remodelling
ERK1/2
Eccentric hypertrophy
Volume overload
Journal
ESC heart failure
ISSN: 2055-5822
Titre abrégé: ESC Heart Fail
Pays: England
ID NLM: 101669191
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
08
04
2019
revised:
29
05
2019
accepted:
18
06
2019
pubmed:
20
7
2019
medline:
2
6
2020
entrez:
20
7
2019
Statut:
ppublish
Résumé
Volume overload (VO) and pressure overload (PO) induce differential cardiac remodelling responses including distinct signalling pathways. Extracellular signal-regulated kinases 1 and 2 (ERK1/2), key signalling components in the mitogen-activated protein kinase (MAPK) pathways, modulate cardiac remodelling during pressure overload (PO). This study aimed to assess their role in VO-induced cardiac remodelling as this was unknown. Aortocaval fistula (Shunt) surgery was performed in mice to induce cardiac VO. Two weeks of Shunt caused a significant reduction of cardiac ERK1/2 activation in wild type (WT) mice as indicated by decreased phosphorylation of the TEY (Thr-Glu-Tyr) motif (-28% as compared with Sham controls, P < 0.05). Phosphorylation of other MAPKs was unaffected. For further assessment, transgenic mice with cardiomyocyte-specific ERK2 overexpression (ERK2tg) were studied. At baseline, cardiac ERK1/2 phosphorylation in ERK2tg mice remained unchanged compared with WT littermates, and no overt cardiac phenotype was observed; however, cardiac expression of the atrial natriuretic peptide was increased on messenger RNA (3.6-fold, P < 0.05) and protein level (3.1-fold, P < 0.05). Following Shunt, left ventricular dilation and hypertrophy were similar in ERK2tg mice and WT littermates. Left ventricular function was maintained, and changes in gene expression indicated reactivation of the foetal gene program in both genotypes. No differences in cardiac fibrosis and kinase activation was found amongst all experimental groups, whereas apoptosis was similarly increased through Shunt in ERK2tg and WT mice. VO-induced eccentric hypertrophy is associated with reduced cardiac ERK1/2 activation in vivo. Cardiomyocyte-specific overexpression of ERK2, however, does not alter cardiac remodelling during VO. Future studies need to define the pathophysiological relevance of decreased ERK1/2 signalling during VO.
Identifiants
pubmed: 31322843
doi: 10.1002/ehf2.12497
pmc: PMC6816056
doi:
Substances chimiques
RNA, Messenger
0
Atrial Natriuretic Factor
85637-73-6
Mapk1 protein, mouse
EC 2.7.11.24
Mitogen-Activated Protein Kinase 1
EC 2.7.11.24
Mitogen-Activated Protein Kinase 3
EC 2.7.11.24
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1015-1026Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : IRTG1816
Pays : International
Organisme : Federal Ministry of Education and Research
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB1002
Pays : International
Organisme : German Centre for Cardiovascular Research
Pays : International
Organisme : British Heart Foundation
ID : RG/13/11/30384
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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