Cardiac hypertrophy or failure? - A systematic evaluation of the transverse aortic constriction model in C57BL/6NTac and C57BL/6J substrains.
C57BL/6
Cardiac hypertrophy
Heart failure
Transverse aortic constriction (TAC)
Journal
Current research in physiology
ISSN: 2665-9441
Titre abrégé: Curr Res Physiol
Pays: Netherlands
ID NLM: 101769251
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
31
07
2019
revised:
20
10
2019
accepted:
21
10
2019
entrez:
24
7
2020
pubmed:
24
7
2020
medline:
24
7
2020
Statut:
ppublish
Résumé
The mouse model of transverse aortic constriction (TAC) has been widely used as a cardiac stress in the investigation of the molecular mechanisms of cardiac hypertrophy. Recently, the International Knockout Mouse Consortium has selected the C57BL/6NTac (BL/6N) mouse strain to generate null alleles for all mouse genes; however, a range of genetic and cardiac phenotypic differences have been reported between this substrain and the commonly used C57BL/6J (BL/6J) substrain. It has been reported by Garcia-Menendez and colleagues that 12-week C57BL/6NTac mice are susceptible to heart failure but little is known about the cardiac remodeling in this substrain as cardiac function progresses from compensation to decompensation. BL/6J and BL/6N mice were subjected to pressure overload via TAC. The impact of both age and duration of cardiac pressure overload induced by TAC on cardiac remodelling were systematically assessed. Our data showed that BL/6N mice developed eccentric hypertrophy with age- and time-dependent deterioration in cardiac function, accompanied by considerable interstitial fibrosis. In contrast, BL/6J mice were more resilient to TAC-induced cardiac stress and developed variable cardiac phenotypes independent of age and the duration of pressure overload. This was likely due to the greater variability in pre-TAC aortic arch dimension as measured by echocardiography. In addition to increased expression of brain natriuretic peptide and collagen gene type 1 and 3, BL/6N mice also had greater angiotensin II type 2 receptor (AT2R) gene expression than BL/6J counterparts at baseline and after 2-weeks TAC, which may contribute to the exacerbated interstitial fibrosis. BL/6N and BL/6J mice have very different responses to TAC stimulation and these differences should be taken into consideration when using the substrains to investigate the mechanisms of hypertrophy and heart failure.
Sections du résumé
BACKGROUND
BACKGROUND
The mouse model of transverse aortic constriction (TAC) has been widely used as a cardiac stress in the investigation of the molecular mechanisms of cardiac hypertrophy. Recently, the International Knockout Mouse Consortium has selected the C57BL/6NTac (BL/6N) mouse strain to generate null alleles for all mouse genes; however, a range of genetic and cardiac phenotypic differences have been reported between this substrain and the commonly used C57BL/6J (BL/6J) substrain. It has been reported by Garcia-Menendez and colleagues that 12-week C57BL/6NTac mice are susceptible to heart failure but little is known about the cardiac remodeling in this substrain as cardiac function progresses from compensation to decompensation.
METHODS
METHODS
BL/6J and BL/6N mice were subjected to pressure overload via TAC. The impact of both age and duration of cardiac pressure overload induced by TAC on cardiac remodelling were systematically assessed.
RESULTS
RESULTS
Our data showed that BL/6N mice developed eccentric hypertrophy with age- and time-dependent deterioration in cardiac function, accompanied by considerable interstitial fibrosis. In contrast, BL/6J mice were more resilient to TAC-induced cardiac stress and developed variable cardiac phenotypes independent of age and the duration of pressure overload. This was likely due to the greater variability in pre-TAC aortic arch dimension as measured by echocardiography. In addition to increased expression of brain natriuretic peptide and collagen gene type 1 and 3, BL/6N mice also had greater angiotensin II type 2 receptor (AT2R) gene expression than BL/6J counterparts at baseline and after 2-weeks TAC, which may contribute to the exacerbated interstitial fibrosis.
CONCLUSIONS
CONCLUSIONS
BL/6N and BL/6J mice have very different responses to TAC stimulation and these differences should be taken into consideration when using the substrains to investigate the mechanisms of hypertrophy and heart failure.
Identifiants
pubmed: 32699840
doi: 10.1016/j.crphys.2019.10.001
pii: S2665-9441(19)30001-X
pmc: PMC7357793
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1-10Subventions
Organisme : Medical Research Council
ID : G1002082
Pays : United Kingdom
Informations de copyright
© 2019 The Authors.
Déclaration de conflit d'intérêts
Authors have no conflicts of interest to disclose.
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